Journal articles on the topic 'Muscles Metabolism Animal models'
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1
Feraco, Alessandra, Stefania Gorini, Andrea Armani, Elisabetta Camajani, Manfredi Rizzo, and Massimiliano Caprio. "Exploring the Role of Skeletal Muscle in Insulin Resistance: Lessons from Cultured Cells to Animal Models." International Journal of Molecular Sciences 22, no. 17 (August 28, 2021): 9327. http://dx.doi.org/10.3390/ijms22179327.
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Skeletal muscle is essential to maintain vital functions such as movement, breathing, and thermogenesis, and it is now recognized as an endocrine organ. Muscles release factors named myokines, which can regulate several physiological processes. Moreover, skeletal muscle is particularly important in maintaining body homeostasis, since it is responsible for more than 75% of all insulin-mediated glucose disposal. Alterations of skeletal muscle differentiation and function, with subsequent dysfunctional expression and secretion of myokines, play a key role in the pathogenesis of obesity, type 2 diabetes, and other metabolic diseases, finally leading to cardiometabolic complications. Hence, a deeper understanding of the molecular mechanisms regulating skeletal muscle function related to energy metabolism is critical for novel strategies to treat and prevent insulin resistance and its cardiometabolic complications. This review will be focused on both cellular and animal models currently available for exploring skeletal muscle metabolism and endocrine function.
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Benton, Carley R., Xiao-Xia Han, Maria Febbraio, Terry E. Graham, and Arend Bonen. "Inverse relationship between PGC-1α protein expression and triacylglycerol accumulation in rodent skeletal muscle." Journal of Applied Physiology 100, no. 2 (February 2006): 377–83. http://dx.doi.org/10.1152/japplphysiol.00781.2005.
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PGC-1α is a key regulator of tissue metabolism, including skeletal muscle. Because it has been shown that PGC-1α alters the capacity for lipid metabolism, it is possible that PGC-1α expression is regulated by the intramuscular lipid milieu. Therefore, we have examined the relationship between PGC-1α protein expression and the intramuscular fatty acid accumulation in hindlimb muscles of animals in which the capacity for fatty acid accumulation in muscle is increased (Zucker obese rat) or reduced [FAT/CD36 null (KO) mice]. Rates of palmitate incorporation into triacylglycerols were determined in perfused red (RG) and white gastrocnemius (WG) muscles of lean and obese Zucker rats and in perfused RG and WG muscles of FAT/CD36 KO and wild-type (WT) mice. In obese Zucker rats, the rate of palmitate incorporation into triacylglycerol depots in RG and WG muscles were 28 and 24% greater than in lean rats ( P < 0.05). In FAT/CD36 KO mice, the rates of palmitate incorporation into triacylglycerol depots were lower in RG (−50%) and WG muscle (−24%) compared with the respective muscles in WT mice ( P < 0.05). In the obese animals, PGC-1α protein content was reduced in both RG (−13%) and WG muscles (−15%) ( P < 0.05). In FAT/CD36 KO mice, PGC-1α protein content was upregulated in both RG (+32%, P < 0.05) and WG muscles (+50%, P < 0.05). In conclusion, from studies in these two animal models, it appears that PGC-1α protein expression is inversely related to components of intramuscular lipid metabolism, because 1) PGC-1α protein expression is downregulated when triacylglycerol synthesis rates, an index of intramuscular lipid metabolism, are increased, and 2) PGC-1α protein expression is upregulated when triacylglycerol synthesis rates are reduced. Therefore, we speculate that the intramuscular lipid sensing may be involved in regulating the protein expression of PGC-1α in skeletal muscle.
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Flis, Damian Jozef, Katarzyna Dzik, Jan Jacek Kaczor, Karol Cieminski, Malgorzata Halon-Golabek, Jedrzej Antosiewicz, Mariusz Roman Wieckowski, and Wieslaw Ziolkowski. "Swim Training Modulates Mouse Skeletal Muscle Energy Metabolism and Ameliorates Reduction in Grip Strength in a Mouse Model of Amyotrophic Lateral Sclerosis." International Journal of Molecular Sciences 20, no. 2 (January 9, 2019): 233. http://dx.doi.org/10.3390/ijms20020233.
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Metabolic reprogramming in skeletal muscles in the human and animal models of amyotrophic lateral sclerosis (ALS) may be an important factor in the diseases progression. We hypothesized that swim training, a modulator of cellular metabolism via changes in muscle bioenergetics and oxidative stress, ameliorates the reduction in muscle strength in ALS mice. In this study, we used transgenic male mice with the G93A human SOD1 mutation B6SJL-Tg (SOD1G93A) 1Gur/J and wild type B6SJL (WT) mice. Mice were subjected to a grip strength test and isolated skeletal muscle mitochondria were used to perform high-resolution respirometry. Moreover, the activities of enzymes involved in the oxidative energy metabolism and total sulfhydryl groups (as an oxidative stress marker) were evaluated in skeletal muscle. ALS reduces muscle strength (−70% between 11 and 15 weeks, p < 0.05), modulates muscle metabolism through lowering citrate synthase (CS) (−30% vs. WT, p = 0.0007) and increasing cytochrome c oxidase and malate dehydrogenase activities, and elevates oxidative stress markers in skeletal muscle. Swim training slows the reduction in muscle strength (−5% between 11 and 15 weeks) and increases CS activity (+26% vs. ALS I, p = 0.0048). Our findings indicate that swim training is a modulator of skeletal muscle energy metabolism with concomitant improvement of skeletal muscle function in ALS mice.
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Miyamoto, Licht, Tatsuro Egawa, Rieko Oshima, Eriko Kurogi, Yosuke Tomida, Koichiro Tsuchiya, and Tatsuya Hayashi. "AICAR stimulation metabolome widely mimics electrical contraction in isolated rat epitrochlearis muscle." American Journal of Physiology-Cell Physiology 305, no. 12 (December 15, 2013): C1214—C1222. http://dx.doi.org/10.1152/ajpcell.00162.2013.
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Physical exercise has potent therapeutic and preventive effects against metabolic disorders. A number of studies have suggested that 5′-AMP-activated protein kinase (AMPK) plays a pivotal role in regulating carbohydrate and lipid metabolism in contracting skeletal muscles, while several genetically manipulated animal models revealed the significance of AMPK-independent pathways. To elucidate significance of AMPK and AMPK-independent signals in contracting skeletal muscles, we conducted a metabolomic analysis that compared the metabolic effects of 5-aminoimidazole-4-carboxamide-1-β-d-ribonucleoside (AICAR) stimulation with the electrical contraction ex vivo in isolated rat epitrochlearis muscles, in which both α1- and α2-isoforms of AMPK and glucose uptake were equally activated. The metabolomic analysis using capillary electrophoresis time-of-flight mass spectrometry detected 184 peaks and successfully annotated 132 small molecules. AICAR stimulation exhibited high similarity to the electrical contraction in overall metabolites. Principal component analysis (PCA) demonstrated that the major principal component characterized common effects whereas the minor principal component distinguished the difference. PCA and a factor analysis suggested a substantial change in redox status as a result of AMPK activation. We also found a decrease in reduced glutathione levels in both AICAR-stimulated and contracting muscles. The muscle contraction-evoked influences related to the metabolism of amino acids, in particular, aspartate, alanine, or lysine, are supposed to be independent of AMPK activation. Our results substantiate the significance of AMPK activation in contracting skeletal muscles and provide novel evidence that AICAR stimulation closely mimics the metabolomic changes in the contracting skeletal muscles.
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Avin, Keith G., Julian A. Vallejo, Neal X. Chen, Kun Wang, Chad D. Touchberry, Marco Brotto, Sarah L. Dallas, Sharon M. Moe, and Michael J. Wacker. "Fibroblast growth factor 23 does not directly influence skeletal muscle cell proliferation and differentiation or ex vivo muscle contractility." American Journal of Physiology-Endocrinology and Metabolism 315, no. 4 (October 1, 2018): E594—E604. http://dx.doi.org/10.1152/ajpendo.00343.2017.
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Skeletal muscle dysfunction accompanies the clinical disorders of chronic kidney disease (CKD) and hereditary hypophosphatemic rickets. In both disorders, fibroblast growth factor 23 (FGF23), a bone-derived hormone regulating phosphate and vitamin D metabolism, becomes chronically elevated. FGF23 has been shown to play a direct role in cardiac muscle dysfunction; however, it is unknown whether FGF23 signaling can also directly induce skeletal muscle dysfunction. We found expression of potential FGF23 receptors ( Fgfr1–4) and α-Klotho in muscles of two animal models (CD-1 and Cy/+ rat, a naturally occurring rat model of chronic kidney disease-mineral bone disorder) as well as C2C12 myoblasts and myotubes. C2C12 proliferation, myogenic gene expression, oxidative stress marker 8-OHdG, intracellular Ca2+ ([Ca2+]i), and ex vivo contractility of extensor digitorum longus (EDL) or soleus muscles were assessed after treatment with various amounts of FGF23. FGF23 (2–100 ng/ml) did not alter C2C12 proliferation, expression of myogenic genes, or oxidative stress after 24- to 72-h treatment. Acute or prolonged FGF23 treatment up to 6 days did not alter C2C12 [Ca2+]i handling, nor did acute treatment with FGF23 (9–100 ng/ml) affect EDL and soleus muscle contractility. In conclusion, although skeletal muscles express the receptors involved in FGF23-mediated signaling, in vitro FGF23 treatments failed to directly alter skeletal muscle development or function under the conditions tested. We hypothesize that other endogenous substances may be required to act in concert with FGF23 or apart from FGF23 to promote muscle dysfunction in hereditary hypophosphatemic rickets and CKD.
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Singh, Himadri, Samuel Joshua Pragasam, and Vijayalakshmi Venkatesan. "Emerging Therapeutic Targets for Metabolic Syndrome: Lessons from Animal Models." Endocrine, Metabolic & Immune Disorders - Drug Targets 19, no. 4 (June 12, 2019): 481–89. http://dx.doi.org/10.2174/1871530319666181130142642.
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Background: Metabolic syndrome is a cluster of medical conditions that synergistically increase the risk of heart diseases and diabetes. The current treatment strategy for metabolic syndrome focuses on treating its individual components. A highly effective agent for metabolic syndrome has yet to be developed. To develop a target for metabolic syndrome, the mechanism encompassing different organs - nervous system, pancreas, skeletal muscle, liver and adipose tissue - needs to be understood. Many animal models have been developed to understand the pathophysiology of metabolic syndrome. Promising molecular targets have emerged while characterizing these animals. Modulating these targets is expected to treat some components of metabolic syndrome. Objective: o discuss the emerging molecular targets in an animal model of metabolic syndrome. Methods: A literature search was performed for the retrieval of relevant articles. Conclusion: Multiple genes/pathways that play important role in the development of Metabolic Syndrome are discussed.
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Katta, Anjaiah, Sunil Kakarla, Miaozong Wu, Satyanarayana Paturi, Murali K. Gadde, Ravikumar Arvapalli, Madhukar Kolli, Kevin M. Rice, and Eric R. Blough. "Altered Regulation of Contraction-Induced Akt/mTOR/p70S6k Pathway Signaling in Skeletal Muscle of the Obese Zucker Rat." Experimental Diabetes Research 2009 (2009): 1–9. http://dx.doi.org/10.1155/2009/384683.
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Increased muscle loading results in the phosphorylation of the 70 kDa ribosomal S6 kinase (p70S6k), and this event is strongly correlated with the degree of muscle adaptation following resistance exercise. Whether insulin resistance or the comorbidities associated with this disorder may affect the ability of skeletal muscle to activate p70S6k signaling following an exercise stimulus remains unclear. Here, we compare the contraction-induced activation of p70S6k signaling in the plantaris muscles of lean and insulin resistant obese Zucker rats following a single bout of increased contractile loading. Compared to lean animals, the basal phosphorylation of p70S6k (Thr389;37.2% and Thr421/Ser424;101.4%), Akt (Thr308;25.1%), and mTOR (Ser2448;63.0%) was higher in obese animals. Contraction increased the phosphorylation of p70S6k (Thr389), Akt (Ser473), and mTOR (Ser2448) in both models however the magnitude and kinetics of activation differed between models. These results suggest that contraction-induced activation of p70S6k signaling is altered in the muscle of the insulin resistant obese Zucker rat.
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Romeu Montenegro, Karina, Milene Amarante Pufal, and Philip Newsholme. "Vitamin D Supplementation and Impact on Skeletal Muscle Function in Cell and Animal Models and an Aging Population: What Do We Know So Far?" Nutrients 13, no. 4 (March 28, 2021): 1110. http://dx.doi.org/10.3390/nu13041110.
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Aging is associated with impairment in skeletal muscle mass and contractile function, predisposing to fat mass gain, insulin resistance and diabetes. The impact of Vitamin D (VitD) supplementation on skeletal muscle mass and function in older adults is still controversial. The aim of this review was to summarize data from randomized clinical trials, animal dietary intervention and cell studies in order to clarify current knowledge on the effects of VitD on skeletal muscle as reported for these three types of experiments. A structured research of the literature in Medline via PubMed was conducted and a total of 43 articles were analysed (cells n = 18, animals n = 13 and humans n = 13). The results as described by these key studies demonstrate, overall, at cell and animal levels, that VitD treatments had positive effects on the development of muscle fibres in cells in culture, skeletal muscle force and hypertrophy. Vitamin D supplementation appears to regulate not only lipid and mitochondrial muscle metabolism but also to have a direct effect on glucose metabolism and insulin driven signalling. However, considering the human perspective, results revealed a predominance of null effects of the vitamin on muscle in the ageing population, but experimental design may have influenced the study outcome in humans. Well-designed long duration double-blinded trials, standardised VitD dosing regimen, larger sample sized studies and standardised measurements may be helpful tools to accurately determine results and compare to those observed in cells and animal dietary intervention models.
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Chen, Yi-Wen, Chris M. Gregory, Mark T. Scarborough, Rongye Shi, Glenn A. Walter, and Krista Vandenborne. "Transcriptional pathways associated with skeletal muscle disuse atrophy in humans." Physiological Genomics 31, no. 3 (November 2007): 510–20. http://dx.doi.org/10.1152/physiolgenomics.00115.2006.
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Disuse atrophy is a common clinical phenomenon that significantly impacts muscle function and activities of daily living. The purpose of this study was to implement genome-wide expression profiling to identify transcriptional pathways associated with muscle remodeling in a clinical model of disuse. Skeletal muscle biopsies were acquired from the medial gastrocnemius in patients with an ankle fracture and from healthy volunteers subjected to 4–11 days of cast immobilization. We identified 277 misregulated transcripts in immobilized muscles of patients, of which the majority were downregulated. The most broadly affected pathways were involved in energy metabolism, mitochondrial function, and cell cycle regulation. We also found decreased expression in genes encoding proteolytic proteins, calpain-3 and calpastatin, and members of the myostatin and IGF-I pathway. Only 26 genes showed increased expression in immobilized muscles, including apolipoprotein (APOD) and leptin receptor (LEPR). Upregulation of APOD (5.0-fold, P < 0.001) and LEPR (5.7-fold, P < 0.05) was confirmed by quantitative RT-PCR and immunohistochemistry. In addition, atrogin-1/MAFbx was found to be 2.4-fold upregulated ( P < 0.005) by quantitative RT-PCR. Interestingly, 96% of the transcripts differentially regulated in immobilized limbs also showed the same trend of change in the contralateral legs of patients but not the contralateral legs of healthy volunteers. Information obtained in this study complements findings in animal models of disuse and provides important feedback for future clinical studies targeting the restoration of muscle function following limb disuse in humans.
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Nadeau, Kristen J., Lindsay B. Ehlers, Lina E. Aguirre, Russell L. Moore, Korinne N. Jew, Heidi K. Ortmeyer, Barbara C. Hansen, Jane E. B. Reusch, and Boris Draznin. "Exercise training and calorie restriction increase SREBP-1 expression and intramuscular triglyceride in skeletal muscle." American Journal of Physiology-Endocrinology and Metabolism 291, no. 1 (July 2006): E90—E98. http://dx.doi.org/10.1152/ajpendo.00543.2005.
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Intramuscular triglyceride (IMTG) deposition in skeletal muscle is associated with obesity and type 2 diabetes (T2DM) and is thought to be related to insulin resistance (IR). Curiously, despite enhanced skeletal muscle insulin sensitivity, highly trained athletes and calorie-restricted (CR) monkeys also have increased IMTG. Sterol regulatory element-binding proteins (SREBPs) are transcription factors that regulate the biosynthesis of cholesterol and fatty acids. SREBP-1 is increased by insulin in skeletal muscle in vitro and in skeletal muscle of IR subjects, but SREBP-1 expression has not been examined in exercise training or calorie restriction. We examined the relationship between IMTG and SREBP-1 expression in animal models of exercise and calorie restriction. Gastrocnemius and soleus muscle biopsies were obtained from 38 Sprague-Dawley rats (18 control and 20 exercise trained). Triglyceride content was higher in the gastrocnemius and soleus muscles of the trained rats. SREBP-1c mRNA, SREBP-1 precursor and mature proteins, and fatty acid synthase (FAS) protein were increased with exercise training. Monkeys ( Macaca mulatta) were CR for a mean of 10.4 years, preventing weight gain and IR. Vastus lateralis muscle was obtained from 12 monkeys (6 CR and 6 controls). SREBP-1 precursor and mature proteins and FAS protein were higher in the CR monkeys. In addition, phosphorylation of ERK1/ERK2 was increased in skeletal muscle of CR animals. In summary, SREBP-1 protein and SREBP-1c mRNA are increased in interventions that increase IMTG despite enhanced insulin sensitivity. CR and exercise-induced augmentation of SREBP-1 expression may be responsible for the increased IMTG seen in skeletal muscle of highly conditioned athletes.
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Charar, Chayki, and Yosef Gruenbaum. "Lamins and metabolism." Clinical Science 131, no. 2 (December 14, 2016): 105–11. http://dx.doi.org/10.1042/cs20160488.
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Lamins are nuclear intermediate filaments (IFs) with important roles in most nuclear activities, including nuclear organization and cell-cycle progression. Mutations in human lamins cause over 17 different diseases, termed laminopathies. Most of these diseases are autosomal dominant and can be roughly divided into four major groups: muscle diseases, peripheral neuronal diseases, accelerated aging disorders and metabolic diseases including Dunnigan type familial partial lipodystrophy (FLPD), acquired partial lipodystrophy (APL) and autosomal dominant leucodystrophy. Mutations in lamins are also associated with the metabolic syndrome (MS). Cells derived from patients suffering from metabolic laminopathies, as well as cells derived from the corresponding animal models, show a disruption of the mechanistic target of rapamycin (mTOR) pathway, abnormal autophagy, altered proliferative rate and down-regulation of genes that regulate adipogenesis. In addition, treating Hutchinson–Gilford progeria syndrome (HGPS) cells with the mTOR inhibitor rapamycin improves their fate. In this review, we will discuss the ways by which lamin genes are involved in the regulation of cell metabolism.
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Nicholson, CD. "Experimental Models of Chronic Lower Extremity Arterial Occlusive Disease: Lessons for Drug Development." Vascular Medicine 1, no. 1 (February 1996): 43–49. http://dx.doi.org/10.1177/1358863x9600100108.
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Peripheral vascular disease is the result of chronic vascular insufficiency. As the vascular insufficiency of the lower limbs progressively deteriorates, the condition progresses from intermittent claudication (pain upon exercise) to pain at rest and gangrene. In very severe cases amputation of the leg may be necessary. Whilst dieting, cessation of smoking and physical exercise all beneficially affect the progression of the disorder, the available drug therapy is of limited benefit. Very effective pharmacological agents capable of alleviating the symptoms of chronic peripheral vascular disease have not been developed. In order to mimic the vascular insufficiency of intermittent claudication, an animal model was developed in rats. This involves short-term and long-term 6–10 weeks ligation of the femoral artery of the rat. As demonstrated using measurements of hindlimb skeletal muscle, blood flow, pO2, metabolism and function, a model of intermittent claudication was produced. Using this model, the beneficial effects of physical training was demonstrated. Physical training induced an increase in blood flow and a greater capacity for aerobic metabolism in the partially ischaemic skeletal muscle. The effect of vasodilators has also been examined in this model; in contrast to agents such as Ca2+ antagonists, K+ channel openers appear to improve nutritional blood flow and metabolism in the afflicted skeletal muscle. This model can also be utilized to demonstrate the effects of haemorrheological interventions and of agents modulating muscle metabolism. However, additional effort is required to develop models for the evaluation of efficacy of antiatherothrombotic drugs.
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Zanatta, Leila C. B., Cesar L. Boguszewski, Victoria Z. C. Borba, and Carolina A. M. Kulak. "Osteocalcin, energy and glucose metabolism." Arquivos Brasileiros de Endocrinologia & Metabologia 58, no. 5 (July 2014): 444–51. http://dx.doi.org/10.1590/0004-2730000003333.
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Osteocalcin is a bone matrix protein that has been associated with several hormonal actions on energy and glucose metabolism. Animal and experimental models have shown that osteocalcin is released into the bloodstream and exerts biological effects on pancreatic beta cells and adipose tissue. Undercarboxylated osteocalcin is the hormonally active isoform and stimulates insulin secretion and enhances insulin sensitivity in adipose tissue and muscle. Insulin and leptin, in turn, act on bone tissue, modulating the osteocalcin secretion, in a traditional feedback mechanism that places the skeleton as a true endocrine organ. Further studies are required to elucidate the role of osteocalcin in the regulation of glucose and energy metabolism in humans and its potential therapeutic implications in diabetes, obesity and metabolic syndrome.
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Myers, T. O., E. J. Messina, A. M. Rodrigues, and M. E. Gerritsen. "Altered aortic and cremaster muscle prostaglandin synthesis in diabetic rats." American Journal of Physiology-Endocrinology and Metabolism 249, no. 4 (October 1, 1985): E374—E379. http://dx.doi.org/10.1152/ajpendo.1985.249.4.e374.
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Alterations in the synthesis and release of prostaglandins have been reported in humans and animal models of diabetes mellitus. In the present study synthesis and release of prostaglandins by thoracic aorta and cremaster muscle of rats with streptozotocin-induced diabetes of 8 wk duration was compared with age-matched controls. Prostaglandin synthesis was assessed by the measurement of immunoreactive prostaglandin E2 (PGE2) and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) release and by quantifying metabolism of exogenous [1-14C]arachidonic acid by thoracic aortic rings and minced cremaster muscle.The cremaster muscles from diabetic rats released significantly greater quantities of PGE2 and 6-keto-PGF1 alpha and PGE2. In contrast, the aortas from diabetic rats released smaller quantities of 6-keto-PGF1 alpha and PGE2 and exhibited reduced 6-[1-14C]keto-PGF1 alpha. These studies indicate that diminished prostacyclin (PGI2) and/or PGE2 production is not a general feature of all diabetic vascular tissues, suggesting that large and small blood vessels may not be similarly affected by diabetes in regard to the metabolism of exogenous arachidonic acid and the synthesis and release of prostaglandins. Furthermore, the vascular changes often observed in conjunction with diabetes, i.e., alterations in vascular reactivity and microangiopathy in small blood vessels and atherosclerosis of large blood vessels may be related in some way to the segmental differences observed in prostaglandin synthesis.
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Brittain, Evan L. "Clinical Trials Targeting Metabolism in Pulmonary Arterial Hypertension." Advances in Pulmonary Hypertension 17, no. 3 (November 1, 2018): 110–14. http://dx.doi.org/10.21693/1933-088x-17.3.110.
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Metabolic derangement is a pathologic feature of pulmonary arterial hypertension (PAH).1 Metabolic abnormalities such as aerobic glycolysis and impaired fatty acid oxidation are consistently observed across different animal models of PAH. Importantly, altered metabolism in human PAH and experimental models is not restricted to the pulmonary vasculature, raising the possibility that PAH is a systemic metabolic disease.2 For example, lipid accumulation is present in the myocardium and skeletal muscle of humans with PAH and the right ventricle exhibits increased glucose uptake compared with matched controls. As a result of these observations, targeting metabolic dysfunction has emerged as an important therapeutic approach for patients with PAH.3 This article will review key aspects of metabolism in PAH, existing metabolic data in humans, and will describe completed and ongoing clinical trials targeting metabolic dysfunction in patients with PAH.
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Marchioretti, Caterina, Emanuela Zuccaro, Udai Bhan Pandey, Jessica Rosati, Manuela Basso, and Maria Pennuto. "Skeletal Muscle Pathogenesis in Polyglutamine Diseases." Cells 11, no. 13 (July 3, 2022): 2105. http://dx.doi.org/10.3390/cells11132105.
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Polyglutamine diseases are characterized by selective dysfunction and degeneration of specific types of neurons in the central nervous system. In addition, nonneuronal cells can also be affected as a consequence of primary degeneration or due to neuronal dysfunction. Skeletal muscle is a primary site of toxicity of polyglutamine-expanded androgen receptor, but it is also affected in other polyglutamine diseases, more likely due to neuronal dysfunction and death. Nonetheless, pathological processes occurring in skeletal muscle atrophy impact the entire body metabolism, thus actively contributing to the inexorable progression towards the late and final stages of disease. Skeletal muscle atrophy is well recapitulated in animal models of polyglutamine disease. In this review, we discuss the impact and relevance of skeletal muscle in patients affected by polyglutamine diseases and we review evidence obtained in animal models and patient-derived cells modeling skeletal muscle.
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Grifone, Raphaëlle, Ming Shao, Audrey Saquet, and De-Li Shi. "RNA-Binding Protein Rbm24 as a Multifaceted Post-Transcriptional Regulator of Embryonic Lineage Differentiation and Cellular Homeostasis." Cells 9, no. 8 (August 12, 2020): 1891. http://dx.doi.org/10.3390/cells9081891.
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RNA-binding proteins control the metabolism of RNAs at all stages of their lifetime. They are critically required for the post-transcriptional regulation of gene expression in a wide variety of physiological and pathological processes. Rbm24 is a highly conserved RNA-binding protein that displays strongly regionalized expression patterns and exhibits dynamic changes in subcellular localization during early development. There is increasing evidence that it acts as a multifunctional regulator to switch cell fate determination and to maintain tissue homeostasis. Dysfunction of Rbm24 disrupts cell differentiation in nearly every tissue where it is expressed, such as skeletal and cardiac muscles, and different head sensory organs, but the molecular events that are affected may vary in a tissue-specific, or even a stage-specific manner. Recent works using different animal models have uncovered multiple post-transcriptional regulatory mechanisms by which Rbm24 functions in key developmental processes. In particular, it represents a major splicing factor in muscle cell development, and plays an essential role in cytoplasmic polyadenylation during lens fiber cell terminal differentiation. Here we review the advances in understanding the implication of Rbm24 during development and disease, by focusing on its regulatory roles in physiological and pathological conditions.
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Grimaldi, P. A. "Roles of PPARΔ in the control of muscle development and metabolism." Biochemical Society Transactions 31, no. 6 (December 1, 2003): 1130–32. http://dx.doi.org/10.1042/bst0311130.
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PPAR δ (peroxisome proliferator-activated receptor δ)-specific agonists decrease plasma lipids and insulinaemia in obese animals. As skeletal muscle is one of the major organs for fatty acid catabolism, we have investigated the roles of the nuclear receptor in the control of muscle development and lipid metabolism, by using two approaches. We have used C2C12 myotubes in which the PPAR δ activity was altered by overexpression of either native or dominant-negative (DN) mutant forms of PPAR δ. Treatment of C2C12 cells by specific PPAR δ agonists promotes expression of genes for proteins of fatty acid catabolism and increases fatty acid oxidation. These responses were increased in C2C12-PPAR δ cells and impaired in C2C12-PPAR δDN cells. We also constructed animal models with muscle-specific expression of PPAR δ (Cre/Lox approach). The effects of muscle-specific alteration of PPAR δ activity were studied on muscle development and metabolism as well as on body fat mass. These experiments indicated that PPAR δ plays a crucial role in myofibre typing determination and regulation of muscle oxidative capabilities, and that muscle-specific overexpression of the nuclear receptor leads to reduction of adipocyte size and body fat mass. These data strongly suggest that PPAR δ controls fatty acid catabolism in muscle and that its activation by synthetic agonists could prevent or correct obesity and type 2 diabetes.
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Girgis, Christian M., Roderick J. Clifton-Bligh, Mark W. Hamrick, Michael F. Holick, and Jenny E. Gunton. "The Roles of Vitamin D in Skeletal Muscle: Form, Function, and Metabolism." Endocrine Reviews 34, no. 1 (November 20, 2012): 33–83. http://dx.doi.org/10.1210/er.2012-1012.
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Abstract Beyond its established role in bone and mineral homeostasis, there is emerging evidence that vitamin D exerts a range of effects in skeletal muscle. Reports of profound muscle weakness and changes in the muscle morphology of adults with vitamin D deficiency have long been described. These reports have been supplemented by numerous trials assessing the impact of vitamin D on muscle strength and mass and falls in predominantly elderly and deficient populations. At a basic level, animal models have confirmed that vitamin D deficiency and congenital aberrations in the vitamin D endocrine system may result in muscle weakness. To explain these effects, some molecular mechanisms by which vitamin D impacts on muscle cell differentiation, intracellular calcium handling, and genomic activity have been elucidated. There are also suggestions that vitamin D alters muscle metabolism, specifically its sensitivity to insulin, which is a pertinent feature in the pathophysiology of insulin resistance and type 2 diabetes. We will review the range of human clinical, animal, and cell studies that address the impact of vitamin D in skeletal muscle, and discuss the controversial issues. This is a vibrant field of research and one that continues to extend the frontiers of knowledge of vitamin D's broad functional repertoire.
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Ota, Hiroyo, Yukio Fujita, Motoo Yamauchi, Shigeo Muro, Hiroshi Kimura, and Shin Takasawa. "Relationship Between Intermittent Hypoxia and Type 2 Diabetes in Sleep Apnea Syndrome." International Journal of Molecular Sciences 20, no. 19 (September 25, 2019): 4756. http://dx.doi.org/10.3390/ijms20194756.
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Sleep apnea syndrome (SAS) is a very common disease involving intermittent hypoxia (IH), recurrent symptoms of deoxygenation during sleep, strong daytime sleepiness, and significant loss of quality of life. A number of epidemiological researches have shown that SAS is an important risk factor for insulin resistance and type 2 diabetes mellitus (DM), which is associated with SAS regardless of age, gender, or body habitus. IH, hallmark of SAS, plays an important role in the pathogenesis of SAS and experimental studies with animal and cellular models indicate that IH leads to attenuation of glucose-induced insulin secretion from pancreatic β cells and to enhancement of insulin resistance in peripheral tissues and cells, such as liver (hepatocytes), adipose tissue (adipocytes), and skeletal muscles (myocytes). In this review, we focus on IH-induced dysfunction in glucose metabolism and its underlying molecular mechanisms in several cells and tissues related to glucose homeostasis.
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Boelen, Anita, Anne H. van der Spek, Flavia Bloise, Emmely M. de Vries, Olga V. Surovtseva, Mieke van Beeren, Mariette T. Ackermans, Joan Kwakkel, and Eric Fliers. "Tissue thyroid hormone metabolism is differentially regulated during illness in mice." Journal of Endocrinology 233, no. 1 (April 2017): 25–36. http://dx.doi.org/10.1530/joe-16-0483.
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Illness induces major modifications in central and peripheral thyroid hormone (TH) metabolism, so-called nonthyroidal illness syndrome (NTIS). As a result, organ-specific changes in local TH availability occur depending on the type and severity of illness. Local TH availability is of importance for the regulation of the tissue-specific TH target genes and determined by the interplay between deiodinating enzymes, TH transport and TH receptor (TR) expression. In the present study, we evaluated changes in TH transport, deiodination and TR expression, the resulting tissue TH concentrations and the expression of TH target genes in liver and muscle in three animal models of illness. We induced (1) acute systemic inflammation by intraperitoneal injection of bacterial endotoxin (LPS), (2) chronic local inflammation by a turpentine injection in the hind limb and (3) severe pneumonia and sepsis by intranasal inoculation with Streptococcus pneumoniae. We found that all aspects of peripheral TH metabolism are differentially regulated during illness, depending on the organ studied and severity of illness. In addition, tissue TH concentrations are not equally affected by the decrease in serum TH concentrations. For example, the decrease in muscle TH concentrations is less severe than the decrease observed in liver. In addition, despite lower TH concentrations in muscle in all three models, muscle T3 action is differentially affected. These observations help to understand the complex nature of the nonthyroidal illness syndrome.
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Berdeaux, Rebecca, and Randi Stewart. "cAMP signaling in skeletal muscle adaptation: hypertrophy, metabolism, and regeneration." American Journal of Physiology-Endocrinology and Metabolism 303, no. 1 (July 1, 2012): E1—E17. http://dx.doi.org/10.1152/ajpendo.00555.2011.
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Among organ systems, skeletal muscle is perhaps the most structurally specialized. The remarkable subcellular architecture of this tissue allows it to empower movement with instructions from motor neurons. Despite this high degree of specialization, skeletal muscle also has intrinsic signaling mechanisms that allow adaptation to long-term changes in demand and regeneration after acute damage. The second messenger adenosine 3′,5′-monophosphate (cAMP) not only elicits acute changes within myofibers during exercise but also contributes to myofiber size and metabolic phenotype in the long term. Strikingly, sustained activation of cAMP signaling leads to pronounced hypertrophic responses in skeletal myofibers through largely elusive molecular mechanisms. These pathways can promote hypertrophy and combat atrophy in animal models of disorders including muscular dystrophy, age-related atrophy, denervation injury, disuse atrophy, cancer cachexia, and sepsis. cAMP also participates in muscle development and regeneration mediated by muscle precursor cells; thus, downstream signaling pathways may potentially be harnessed to promote muscle regeneration in patients with acute damage or muscular dystrophy. In this review, we summarize studies implicating cAMP signaling in skeletal muscle adaptation. We also highlight ligands that induce cAMP signaling and downstream effectors that are promising pharmacological targets.
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Liu, Ying, Simon Chewchuk, Charles Lavigne, Sophie Brûlé, Genevieve Pilon, Vanessa Houde, Aimin Xu, Andre Marette, and Gary Sweeney. "Functional significance of skeletal muscle adiponectin production, changes in animal models of obesity and diabetes, and regulation by rosiglitazone treatment." American Journal of Physiology-Endocrinology and Metabolism 297, no. 3 (September 2009): E657—E664. http://dx.doi.org/10.1152/ajpendo.00186.2009.
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Endocrine effects of adipose-derived adiponectin on skeletal muscle have been shown to account, at least in part, for the anti-diabetic effects of this adipokine. Recently, the concept of myokines has gained credence, and the potential for skeletal muscle to produce adiponectin has been suggested. Here we demonstrated an increased level of adiponectin mRNA and protein expression as well as protein secretion in response to rosiglitazone treatment in L6 muscle cells. This correlated with the ability of rosiglitazone to enhance insulin sensitivity for stimulation of protein kinase B (Akt) phosphorylation and glucose transport; rosiglitazone also corrected high-glucose-induced insulin resistance in L6 cells. Overexpression of adiponectin confirmed the functional significance of local production of adiponectin in muscle cells via elevated glucose uptake and increased insulin sensitivity. In obese diabetic db/db mice, there was a change in the adiponectin expression profile in soleus and extensor digitorum longus (EDL) muscle with less high molecular weight (HMW) and more medium (MMW)/low (LMW) molecular weight species detected. Induction of obesity and insulin resistance in rats by feeding a high-fat high-sucrose diet also led to decreased muscle HMW adiponectin content that could be corrected by rosiglitazone treatment. In summary, we show the ability of skeletal muscle cells to produce adiponectin, which can mediate autocrine metabolic effects, thus establishing adiponectin as a bona fide myokine. We also demonstrate that skeletal muscle adiponectin production is altered in animal models of obesity and diabetes and that these changes can be corrected by rosiglitazone.
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De Toni, Luca, Kenda Jawich, Maurizio De Rocco Ponce, Andrea Di Nisio, and Carlo Foresta. "Osteocalcin: A Protein Hormone Connecting Metabolism, Bone and Testis Function." Protein & Peptide Letters 27, no. 12 (December 2, 2020): 1268–75. http://dx.doi.org/10.2174/0929866527666200505220459.
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During the last decade, the disclosure of systemic effects of osteocalcin (OCN) in its undercarboxylated form contributed to switch the concept of bone from a merely structural apparatus to a fully endocrine organ involved in the regulation of systemic functions. Since that time, the role of OCN as osteokine has been more and more widened appreciated and detailed by the major use of animal models, starting from the original function in the bone extracellular matrix as Gla-protein and spanning from the protective effects towards weight gain, insulin sensitivity and glucose homeostasis, to the anabolic and metabolic roles in skeletal muscle, to the stimulating effects on the testis endocrine function and male fertility, to the most recent preservation from anxious and depressive states through a direct activity on the central nervous system. In this review, experimental data supporting the inter-organ communication roles of this protein are discussed, together with the available data supporting the consistency between experimental data obtained in animals and those reported in humans. In addition, a specific session has been devoted to the possible significance the OCN as a template agonist on its receptor GPRC6A, for the development of novel therapeutic and pharmacological approaches for the treatment of dismetabolic states and male infertility.
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Genders, Amanda J., Graham P. Holloway, and David J. Bishop. "Are Alterations in Skeletal Muscle Mitochondria a Cause or Consequence of Insulin Resistance?" International Journal of Molecular Sciences 21, no. 18 (September 22, 2020): 6948. http://dx.doi.org/10.3390/ijms21186948.
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As a major site of glucose uptake following a meal, skeletal muscle has an important role in whole-body glucose metabolism. Evidence in humans and animal models of insulin resistance and type 2 diabetes suggests that alterations in mitochondrial characteristics accompany the development of skeletal muscle insulin resistance. However, it is unclear whether changes in mitochondrial content, respiratory function, or substrate oxidation are central to the development of insulin resistance or occur in response to insulin resistance. Thus, this review will aim to evaluate the apparent conflicting information placing mitochondria as a key organelle in the development of insulin resistance in skeletal muscle.
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Shafrir, Eleazar. "Albert Renold Memorial Lecture: Molecular Background of Nutritionally Induced Insulin Resistance Leading to Type 2 Diabetes – From Animal Models to Humans." International Journal of Experimental Diabetes Research 2, no. 4 (2001): 299–319. http://dx.doi.org/10.1155/edr.2001.299.
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Albert Renold strived to gain insight into the abnormalities of human diabetes by defining the pathophysiology of the disease peculiar to a given animal. He investigated the Israeli desert-derived spiny mice (Acomys cahirinus), which became obese on fat-rich seed diet. After a few months hyperplasia and hypertrophy ofβ-cells occurred leading to a sudden rupture, insulin loss and ketosis. Spiny mice were low insulin responders, which is probably a characteristic of certain desert animals, protecting against insulin oversecretion when placed on an abundant diet. We have compared the response to overstimulation of several mutant diabetic species and nutritionally induced nonmutant animals when placed on affluent diet. Some endowed with resilientβ-cells sustain long-lasting oversecretion, compensating for the insulin resistance, without lapsing into overt diabetes. Some with labile beta cells exhibit apoptosis and lose their capacity of coping with insulin resistance after a relatively short period. The wide spectrum of response to insulin resistance among different diabetes prone species seems to represent the varying response of human beta cells among the populations. In search for the molecular background of insulin resistance resulting from overnutrition we have studied the Israeli desert gerbil Psammomys obesus (sand rat), which progresses through hyperinsulinemia, followed by hyperglycemia and irreversible beta cell loss. Insulin resistance was found to be the outcome of reduced activation of muscle insulin receptor tyrosine kinase by insulin, in association with diminished GLUT4 protein and DNA content and overexpression of PKC isoenzymes, notably of PKCε. This overexpression and translocation to the membrane was discernible even prior to hyperinsulinemia and may reflect the propensity to diabetes in nondiabetic species and represent a marker for preventive action. By promoting the phosphorylation of serine/threonine residues on certain proteins of the insulin signaling pathway, PKCεexerts a negative feedback on insulin action. PKCεwas also found to attenuate the activity of PKB and to promote the degradation of insulin receptor, as determined by co-incubation in HEK 293 cells. PKCεoverexpression was related to the rise in muscle diacylglycerol and lipid content, which are prevalent on lascivious nutrition especially if fat-rich. Thus, Psammomys illustrates the probable antecedents of the development of worldwide diabetes epidemic in human populations emerging from food scarcity to nutritional affluence, inappriopriate to their metabolic capacity.
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Nappi, Annarita, Melania Murolo, Annunziata Gaetana Cicatiello, Serena Sagliocchi, Emery Di Cicco, Maddalena Raia, Mariano Stornaiuolo, Monica Dentice, and Caterina Miro. "Thyroid Hormone Receptor Isoforms Alpha and Beta Play Convergent Roles in Muscle Physiology and Metabolic Regulation." Metabolites 12, no. 5 (April 29, 2022): 405. http://dx.doi.org/10.3390/metabo12050405.
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Skeletal muscle is a key energy-regulating organ, skilled in rapidly boosting the rate of energy production and substrate consumption following increased workload demand. The alteration of skeletal muscle metabolism is directly associated with numerous pathologies and disorders. Thyroid hormones (THs) and their receptors (TRs, namely, TRα and TRβ) exert pleiotropic functions in almost all cells and tissues. Skeletal muscle is a major THs-target tissue and alterations of THs levels have multiple influences on the latter. However, the biological role of THs and TRs in orchestrating metabolic pathways in skeletal muscle has only recently started to be addressed. The purpose of this paper is to investigate the muscle metabolic response to TRs abrogation, by using two different mouse models of global TRα- and TRβKO. In line with the clinical features of resistance to THs syndromes in humans, characterized by THRs gene mutations, both animal models of TRs deficiency exhibit developmental delay and mitochondrial dysfunctions. Moreover, using transcriptomic and metabolomic approaches, we found that the TRs–THs complex regulates the Fatty Acids (FAs)-binding protein GOT2, affecting FAs oxidation and transport in skeletal muscle. In conclusion, these results underline a new metabolic role of THs in governing muscle lipids distribution and metabolism.
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Yu, Hong, Rajeshwari D. Koilkonda, Tsung-Han Chou, Vittorio Porciatti, Arpit Mehta, Ian D. Hentall, Vince A. Chiodo, et al. "Consequences of zygote injection and germline transfer of mutant human mitochondrial DNA in mice." Proceedings of the National Academy of Sciences 112, no. 42 (October 5, 2015): E5689—E5698. http://dx.doi.org/10.1073/pnas.1506129112.
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Considerable evidence supports mutations in mitochondrial genes as the cause of maternally inherited diseases affecting tissues that rely primarily on oxidative energy metabolism, usually the nervous system, the heart, and skeletal muscles. Mitochondrial diseases are diverse, and animal models currently are limited. Here we introduced a mutant human mitochondrial gene responsible for Leber hereditary optic neuropathy (LHON) into the mouse germ line using fluorescence imaging for tissue-specific enrichment in the target retinal ganglion cells. A mitochondria-targeted adeno-associated virus (MTS-AAV) containing the mutant human NADH ubiquinone oxidoreductase subunit 4 (ND4) gene followed by mitochondrial-encodedmCherrywas microinjected into zygotes. Female founders with mCherry fluorescence on ophthalmoscopy were backcrossed with normal males for eight generations. Mutant humanND4DNA was 20% of mouseND4and did not integrate into the host genome. Translated human ND4 protein assembled into host respiratory complexes, decreasing respiratory chain function and increasing oxidative stress. Swelling of the optic nerve head was followed by progressive demise of ganglion cells and their axons, the hallmarks of human LHON. Early visual loss that began at 3 mo and progressed to blindness 8 mo after birth was reversed by intraocular injection of MTS-AAV expressing wild-type humanND4. The technology of introducing human mitochondrial genes into the mouse germ line has never been described, to our knowledge, and has implications not only for creating animal models recapitulating the counterpart human disorder but more importantly for reversing the adverse effects of the mutant gene using gene therapy to deliver the wild-type allele.
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Yamamoto, Toshihiro, Hiroshi Yamaguchi, Hiroshi Miki, Shuji Kitamura, Yoshihisa Nakada, Thomas D. Aicher, Scott A. Pratt, and Koki Kato. "A novel coenzyme A:diacylglycerol acyltransferase 1 inhibitor stimulates lipid metabolism in muscle and lowers weight in animal models of obesity." European Journal of Pharmacology 650, no. 2-3 (January 2011): 663–72. http://dx.doi.org/10.1016/j.ejphar.2010.10.040.
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Gammone, Maria, Graziano Riccioni, Gaspare Parrinello, and Nicolantonio D’Orazio. "Omega-3 Polyunsaturated Fatty Acids: Benefits and Endpoints in Sport." Nutrients 11, no. 1 (December 27, 2018): 46. http://dx.doi.org/10.3390/nu11010046.
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The influence of nutrition has the potential to substantially affect physical function and body metabolism. Particular attention has been focused on omega-3 polyunsaturated fatty acids (n-3 PUFAs), which can be found both in terrestrial features and in the marine world. They are responsible for numerous cellular functions, such as signaling, cell membrane fluidity, and structural maintenance. They also regulate the nervous system, blood pressure, hematic clotting, glucose tolerance, and inflammatory processes, which may be useful in all inflammatory conditions. Animal models and cell-based models show that n-3 PUFAs can influence skeletal muscle metabolism. Furthermore, recent human studies demonstrate that they can influence not only the exercise and the metabolic response of skeletal muscle, but also the functional response for a period of exercise training. In addition, their potential anti-inflammatory and antioxidant activity may provide health benefits and performance improvement especially in those who practice physical activity, due to their increased reactive oxygen production. This review highlights the importance of n-3 PUFAs in our diet, which focuses on their potential healthy effects in sport.
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Niels, Timo, Annika Tomanek, Nils Freitag, and Moritz Schumann. "Can Exercise Counteract Cancer Cachexia? A Systematic Literature Review and Meta-Analysis." Integrative Cancer Therapies 19 (January 2020): 153473542094041. http://dx.doi.org/10.1177/1534735420940414.
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Background: Cancer-cachexia is associated with chronic inflammation, impaired muscle metabolism and body mass loss, all of which are classical targets of physical exercise. Objectives: This systematic review and meta-analysis aimed to determine the effects of exercise on body and muscle mass in cachectic cancer hosts. Data Sources: PubMed/Medline, EMBASE, CINHAL, ISI Web of Science, and Cochrane Library were searched until July 2019. Study Selection: Trials had to be randomized controlled trials or controlled trials including cancer patients or animal models with cachexia-inducing tumors. Only sole exercise interventions over at least 7 days performed in a controlled environment were included. Data Extraction: Risk of bias was assessed and a random-effects model was used to pool effect sizes by standardized mean differences (SMD). Results: All eligible 20 studies were performed in rodents. Studies prescribed aerobic (n = 15), strength (n = 3) or combined training (n = 2). No statistical differences were observed for body mass and muscle weight of the gastrocnemius, soleus, and tibialis muscles between the exercise and control conditions (SMD = ‒0.05, 95%CI-0.64-0.55, P = 0.87). Exercise duration prior to tumor inoculation was a statistical moderator for changes in body mass under tumor presence ( P = 0.04). Limitations: No human trials were identified. A large study heterogeneity was present, probably due to different exercise modalities and outcome reporting. Conclusion: Exercise does not seem to affect cancer-cachexia in rodents. However, the linear regression revealed that exercise duration prior to tumor inoculation led to reduced cachexia-severity, possibly strengthening the rationale for the use of exercise in cancer patients at cachexia risk.
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Govoni, Kristen E. "261 Effects of Dam Nutrition on Offspring Metabolism." Journal of Animal Science 99, Supplement_3 (October 8, 2021): 138. http://dx.doi.org/10.1093/jas/skab235.253.
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Abstract Maternal diet during gestation is important for proper fetal growth and development. There is evidence that poor maternal nutrition (restricted- and over-feeding) can alter growth of the fetus with long-term consequences on postnatal growth and adult maintenance. Additionally, maternal diet can program offspring for altered metabolism which leads to increased fat deposition and likely reduced efficiency of production later in life. Using livestock models, we and others have demonstrated insulin resistance, leptin resistance, and increased adiposity in response to poor maternal nutrition. These systemic changes are likely due to altered metabolic regulation at the tissue level. Using a sheep model, we have evidence that poor maternal nutrition also alters key metabolic profiles in muscle and liver, key metabolic tissues, in offspring. Specifically, in offspring of restricted-fed ewes, similar profiles of amino acid (e.g. branched-chain amino acids, histidine, methionine) and lipid (e.g. triglycerides) metabolites were altered in blood, liver, and muscle. In the muscle of offspring from restricted- and over-fed ewes, lipid and protein metabolic profiles diverged between the two treatment groups. This demonstrates different mechanisms contributing to altered metabolism of offspring from ewes restricted- and over-fed during gestation. The similar changes in metabolic profiles at both the systemic and local level suggest complex mechanisms involved in metabolic dysregulation of offspring from poorly fed mothers, which likely contribute to life-long metabolic dysregulation and reduced efficiency of growth and product quality.
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Ordaz, Gerardo, Jos a, and Gerardo Mariscal. "Characterization and modeling of the serum concentration of osteocalcin in breeding sows and its interaction with biochemical indicators: A review." Journal of Advanced Veterinary and Animal Research 9, no. 4 (2022): 634. http://dx.doi.org/10.5455/javar.2022.i633.
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Adipose, muscle, and bone tissues modulate the metabolic state of mammals. However, the role of bone tissue as a metabolic state modulator in sows has not been studied. During the gestation–lactation transition, sows undergo metabolic adaptations to meet their nutritional requirements. Among these adaptations, bone remodeling is characterized by the synthesis and inhibition of hormones that participate, together with hormones from other tissues, in fetal development and lactogenesis. Osteocalcin is a hormone synthesized by the bone tissue which has been associated in different biological models with the improvement of the metabolic state. However, in sows, published results on the concentration of osteocalcin are scarce, and its concentration throughout the reproductive cycle is unknown. Therefore, with information from published trials on the measurement of serum osteocalcin, a structured review was conducted under the following objectives: (1) to review the promising effect of osteocalcin on energy metabolism in different models and (2) to characterize and model the serum concentrations of osteocalcin during the reproductive cycle of the sow. According to the review, the results obtained for humans and other animal models suggest that osteocalcin regulates energy metabolism, which has been associated with the need for integrated metabolism to cope with the metabolic demand during gestation and lactation in mammals. If these effects are significant in the sow, current recommendations for dietary balance should be reconsidered, particularly during the gestation–lactation transition period. According to mathematical modeling, it was the period in which the lowest concentration of osteocalcin was found.
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Yates, D. T., A. R. Macko, M. Nearing, X. Chen, R. P. Rhoads, and S. W. Limesand. "Developmental Programming in Response to Intrauterine Growth Restriction Impairs Myoblast Function and Skeletal Muscle Metabolism." Journal of Pregnancy 2012 (2012): 1–10. http://dx.doi.org/10.1155/2012/631038.
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Fetal adaptations to placental insufficiency alter postnatal metabolic homeostasis in skeletal muscle by reducing glucose oxidation rates, impairing insulin action, and lowering the proportion of oxidative fibers. In animal models of intrauterine growth restriction (IUGR), skeletal muscle fibers have less myonuclei at birth. This means that myoblasts, the sole source for myonuclei accumulation in fibers, are compromised. Fetal hypoglycemia and hypoxemia are complications that result from placental insufficiency. Hypoxemia elevates circulating catecholamines, and chronic hypercatecholaminemia has been shown to reduce fetal muscle development and growth. We have found evidence for adaptations in adrenergic receptor expression profiles in myoblasts and skeletal muscle of IUGR sheep fetuses with placental insufficiency. The relationship ofβ-adrenergic receptors shifts in IUGR fetuses because Adrβ2 expression levels decline and Adrβ1 expression levels are unaffected in myofibers and increased in myoblasts. This adaptive response would suppress insulin signaling, myoblast incorporation, fiber hypertrophy, and glucose oxidation. Furthermore, thisβ-adrenergic receptor expression profile persists for at least the first month in IUGR lambs and lowers their fatty acid mobilization. Developmental programming of skeletal muscle adrenergic receptors partially explains metabolic and endocrine differences in IUGR offspring, and the impact on metabolism may result in differential nutrient utilization.
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Li, SiJin, Ping Liu, XiaoTeng Feng, YiRu Wang, Min Du, and JiaRou Wang. "The role and mechanism of tetramethylpyrazine for atherosclerosis in animal models: A systematic review and meta-analysis." PLOS ONE 17, no. 5 (May 2, 2022): e0267968. http://dx.doi.org/10.1371/journal.pone.0267968.
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Background Atherosclerosis(AS) is widely recognized as a risk factor for incident cardiovascular and cerebrovascular diseases. Tetramethylpyrazine (TMP) is the active ingredient of Ligusticum wallichii that possesses a variety of biological activities against atherosclerosis. Objective This systematic review and meta-analysis sought to study the impact of and mechanism of tetramethylpyrazine for atherosclerosis in animal models. Methods A systematic search was conducted of PubMed, Embase, Cochrane Library, Web of Science database, Chinese Biomedical (CBM) database, China National Knowledge Infrastructure (CNKI), WanFang data, and Vip Journal Integration Platform, covering the period from the respective start date of each database to December 2021. We used SYRCLE’s 10-item checklist and Rev-Man 5.3 software to analyze the data and the risk of bias. Results Twelve studies, including 258 animals, met the inclusion criteria. Compared with the control group, TMP significantly reduced aortic atherosclerotic lesion area, and induced significant decreases in levels of TC (SMD = ‐2.67, 95% CI -3.68 to -1.67, P < 0.00001), TG (SMD = ‐2.43, 95% CI -3.39 to -1.47, P < 0.00001), and LDL-C (SMD = ‐2.87, 95% CI -4.16 to -1.58, P < 0.00001), as well as increasing HDL-C (SMD = 2.04, 95% CI 1.05 to 3.03, P = 0.001). TMP also significantly modulated plasma inflammatory responses and biological signals associated with atherosclerosis. In subgroup analysis, the groups of high-dose TMP (≥50 mg/kg) showed better results than those of the control group. No difference between various durations of treatment groups or various assessing location groups. Conclusion TMP exerts anti-atherosclerosis functions in an animal model of AS mediated by anti-inflammatory action, antioxidant action, ameliorating lipid metabolism disorder, protection of endothelial function, antiplatelet activity, reducing the proliferation and migration of smooth muscle cells, inhibition of angiogenesis, antiplatelet aggregation. Due to the limitations of the quantity and quality of current studies, the above conclusions need to be verified by more high-quality studies. Trial registration number PROSPERO registration no.CRD42021288874.
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Watson, Katherine S., Imane Boukhloufi, Melissa Bowerman, and Simon H. Parson. "The Relationship between Body Composition, Fatty Acid Metabolism and Diet in Spinal Muscular Atrophy." Brain Sciences 11, no. 2 (January 20, 2021): 131. http://dx.doi.org/10.3390/brainsci11020131.
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Spinal muscular atrophy (SMA) is an autosomal recessive condition that results in pathological deficiency of the survival motor neuron (SMN) protein. SMA most frequently presents itself within the first few months of life and is characterized by progressive muscle weakness. As a neuromuscular condition, it prominently affects spinal cord motor neurons and the skeletal muscle they innervate. However, over the past few decades, the SMA phenotype has expanded to include pathologies outside of the neuromuscular system. The current therapeutic SMA landscape is at a turning point, whereby a holistic multi-systemic approach to the understanding of disease pathophysiology is at the forefront of fundamental research and translational endeavours. In particular, there has recently been a renewed interest in body composition and metabolism in SMA patients, specifically that of fatty acids. Indeed, there is increasing evidence of aberrant fat distribution and fatty acid metabolism dysfunction in SMA patients and animal models. This review will explore fatty acid metabolic defects in SMA and discuss how dietary interventions could potentially be used to modulate and reduce the adverse health impacts of these perturbations in SMA patients.
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Moresi, Viviana, Alessandra Renzini, Giorgia Cavioli, Marilia Seelaender, Dario Coletti, Giuseppe Gigli, and Alessia Cedola. "Functional Nutrients to Ameliorate Neurogenic Muscle Atrophy." Metabolites 12, no. 11 (November 21, 2022): 1149. http://dx.doi.org/10.3390/metabo12111149.
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Neurogenic muscle atrophy is a debilitating condition that occurs from nerve trauma in association with diseases or during aging, leading to reduced interaction between motoneurons and skeletal fibers. Current therapeutic approaches aiming at preserving muscle mass in a scenario of decreased nervous input include physical activity and employment of drugs that slow down the progression of the condition yet provide no concrete resolution. Nutritional support appears as a precious tool, adding to the success of personalized medicine, and could thus play a relevant part in mitigating neurogenic muscle atrophy. We herein summarize the molecular pathways triggered by denervation of the skeletal muscle that could be affected by functional nutrients. In this narrative review, we examine and discuss studies pertaining to the use of functional ingredients to counteract neurogenic muscle atrophy, focusing on their preventive or curative means of action within the skeletal muscle. We reviewed experimental models of denervation in rodents and in amyotrophic lateral sclerosis, as well as that caused by aging, considering the knowledge generated with use of animal experimental models and, also, from human studies.
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Small, Lewin, Henry Gong, Christian Yassmin, Gregory J. Cooney, and Amanda E. Brandon. "Thermoneutral housing does not influence fat mass or glucose homeostasis in C57BL/6 mice." Journal of Endocrinology 239, no. 3 (December 2018): 313–24. http://dx.doi.org/10.1530/joe-18-0279.
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One major factor affecting physiology often overlooked when comparing data from animal models and humans is the effect of ambient temperature. The majority of rodent housing is maintained at ~22°C, the thermoneutral temperature for lightly clothed humans. However, mice have a much higher thermoneutral temperature of ~30°C, consequently data collected at 22°C in mice could be influenced by animals being exposed to a chronic cold stress. The aim of this study was to investigate the effect of housing temperature on glucose homeostasis and energy metabolism of mice fed normal chow or a high-fat, obesogenic diet (HFD). Male C57BL/6J(Arc) mice were housed at standard temperature (22°C) or at thermoneutrality (29°C) and fed either chow or a 60% HFD for 13 weeks. The HFD increased fat mass and produced glucose intolerance as expected but this was not exacerbated in mice housed at thermoneutrality. Changing the ambient temperature, however, did alter energy expenditure, food intake, lipid content and glucose metabolism in skeletal muscle, liver and brown adipose tissue. Collectively, these findings demonstrate that mice regulate energy balance at different housing temperatures to maintain whole-body glucose tolerance and adiposity irrespective of the diet. Despite this, metabolic differences in individual tissues were apparent. In conclusion, dietary intervention in mice has a greater impact on adiposity and glucose metabolism than housing temperature although temperature is still a significant factor in regulating metabolic parameters in individual tissues.
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Parise, Gianni, Ciara E. O’Reilly, and Michael A. Rudnicki. "Molecular regulation of myogenic progenitor populations." Applied Physiology, Nutrition, and Metabolism 31, no. 6 (December 2006): 773–81. http://dx.doi.org/10.1139/h06-055.
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Skeletal muscle regeneration and adaptation to exercise require the actions of muscle satellite cells. Muscle satellite cells are thought to play an integral role in the process of exercise adaptation, but have also been shown to possess the capacity to fully regenerate muscle tissue following destructive muscle injury. We now know that molecular regulation of satellite cells involves the coordinated actions of a series of transcriptional networks that leads to myogenic commitment, cell-cycle entry, proliferation, and terminal differentiation. Additionally, Pax7 is a paired-box transcription factor that has been identified as playing a critical role in satellite cell regulation. It remains debatable, however, whether Pax7 is required for the specification of satellite cells and (or) whether it is playing a vital role in self-renewal and maintenance of the satellite cell population. In recent years, the emergence of atypical myogenic progenitor populations has added a new dimension to muscle repair, and significant interest has been focused on identifying populations such as bone-marrow-derived stem cells that have the ability to contribute to muscle. Interestingly, elucidating the molecular regulation of myogenic progenitor populations has involved animal models of muscle regeneration, with questionable relevance for human muscle adaptation to exercise. This paper highlights the current state of knowledge on the molecular regulation of satellite cells, explores the potential contribution of atypical myogenic progenitors, and discusses the information gathered from animal regeneration models in terms of its relevance to the process of exercise adaptation.
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He, Shiyi, Lu Yan, Rongxin Zhu, Hao Wei, Jianxiong Wang, Lan Zheng, and Ying Zhang. "Skeletal-Muscle-Specific Overexpression of Chrono Leads to Disruption of Glucose Metabolism and Exercise Capacity." Life 12, no. 8 (August 15, 2022): 1233. http://dx.doi.org/10.3390/life12081233.
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Disruption of circadian rhythms is related to disorders of glucose metabolism, and the molecular clock also exists in skeletal muscle. The ChIP-derived repressor of network oscillator (Chrono) and brain and muscle ARNT-like 1 (Bmal1) are core circadian components. Chrono is considered to be the repressor of Bmal1, and the Chrono–Bmal1 pathway is important in regulating the circadian rhythm; it has been speculated that this pathway could be a new mechanism for regulating glucose metabolism. The purpose of this study was to investigate the effects of Chrono on glucose metabolism in skeletal muscle and exercise capacity by using mice with skeletal-muscle-specific overexpression of Chrono (Chrono TG) and wild-type (WT) mice as the animal models. The results of this cross-sectional study indicated that the Chrono TG mice had an impaired glucose tolerance, lower exercise capacity, and higher levels of nonfasted blood glucose and glycogen content in skeletal muscle compared to WT mice. In addition, the Chrono TG mice also showed a significant increase in the amount of Chrono bound to Bmal1 according to a co-IP analysis; a remarkable decrease in mRNA expression of Tbc1d1, Glut4, Hk2, Pfkm, Pdp1, Gbe1, and Phka1, as well as in activity of Hk and protein expression of Ldhb; but higher mRNA expression of Pdk4 and protein expression of Ldha compared with those of WT mice. These data suggested the skeletal-muscle-specific overexpression of Chrono led to a greater amount of Chrono bound to Bmal1, which then could affect the glucose transporter, glucose oxidation, and glycogen utilization in skeletal muscle, as well as exercise capacity.
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McLendon, Patrick M., and Jeffrey Robbins. "Desmin-related cardiomyopathy: an unfolding story." American Journal of Physiology-Heart and Circulatory Physiology 301, no. 4 (October 2011): H1220—H1228. http://dx.doi.org/10.1152/ajpheart.00601.2011.
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The intermediate filament protein desmin is an integral component of the cardiomyocyte and serves to maintain the overall structure and cytoskeletal organization within striated muscle cells. Desmin-related myopathy can be caused by mutations in desmin or associated proteins, which leads to intracellular accumulation of misfolded protein and production of soluble pre-amyloid oligomers, which leads to weakened skeletal and cardiac muscle. In this review, we examine the cellular phenotypes in relevant animal models of desmin-related cardiomyopathy. These models display characteristic sarcoplasmic protein aggregates. Aberrant protein aggregation leads to mitochondrial dysfunction, abnormal metabolism, and altered cardiomyocyte structure. These deficits to cardiomyocyte function may stem from impaired cellular proteolytic mechanisms. The data obtained from these models allow a more complete picture of the pathology in desmin-related cardiomyopathy to be described. Moreover, these studies highlight the importance of desmin in maintaining cardiomyocyte structure and illustrate how disrupting this network can be deleterious to the heart. We emphasize the similarities observed between desmin-related cardiomyopathy and other protein conformational disorders and speculate that therapies to treat this disease may be broadly applicable to diverse protein aggregation-based disorders.
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Willsky, Gail R., Lai-Har Chi, Yulan Liang, Daniel P. Gaile, Zihua Hu, and Debbie C. Crans. "Diabetes-altered gene expression in rat skeletal muscle corrected by oral administration of vanadyl sulfate." Physiological Genomics 26, no. 3 (August 2006): 192–201. http://dx.doi.org/10.1152/physiolgenomics.00196.2005.
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Treatment with vanadium, a representative of a class of antidiabetic compounds, alleviates diabetic hyperglycemia and hyperlipidemia. Oral administration of vanadium compounds in animal models and humans does not cause clinical symptoms of hypoglycemia, a common problem for diabetic patients with insulin treatment. Gene expression, using Affymetrix arrays, was examined in muscle from streptozotocin-induced diabetic and normal rats in the presence or absence of oral vanadyl sulfate treatment. This treatment affected normal rats differently from diabetic rats, as demonstrated by two-way ANOVA of the full array data. Diabetes altered the expression of 133 genes, and the expression of 30% of these genes dysregulated in diabetes was normalized by vanadyl sulfate treatment. For those genes, the ratio of expression in normal animals to the expression in diabetic animals showed a strong negative correlation with the ratio of expression in diabetic animals to the expression in diabetic animals treated with vanadyl sulfate ( P = −0.85). The genes identified belong to six major metabolic functional groups: lipid metabolism, oxidative stress, muscle structure, protein breakdown and biosynthesis, the complement system, and signal transduction. The identification of oxidative stress genes, coupled with the known oxidative chemistry of vanadium, implicates reactive oxygen species in the action of this class of compounds. These results imply that early transition metals or compounds formed from their chemical interactions with other metabolites may act as general transcription modulators, a role not usually associated with this class of compounds.
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Clark, Audra, Ryan M. Huebinger, Deborah L. Carlson, Steven E. Wolf, and Juquan Song. "Serum Level of Musclin Is Elevated Following Severe Burn." Journal of Burn Care & Research 40, no. 5 (June 11, 2019): 535–40. http://dx.doi.org/10.1093/jbcr/irz101.
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Abstract Muscle wasting induced by severe burn worsens clinical outcomes is associated with hyperglycemia. A novel muscle-specific secretory factor, musclin, was reported to regulate glucose metabolism with a homologous sequence of natriuretic peptides. The purpose of the study was to investigate musclin expression in response to burn injury in both human and animal models. Serum was collected from 13 adult burn patients and circulating levels of musclin protein were measured via elisa. The cytokine profile was measured by Bio-Plex multiple immunoassay. Following the clinical study, we used a burn rat model with 40% TBSA to study the time course of musclin expression till day 14. Rat serum and muscle tissue sample were harvested. Finally, an in vitro study was applied to investigate whether the muscle cell C2C12 myoblast expressed musclin under 10% burn serum stimulation. Pearson analysis showed that there was a significant positive correlation of musclin expression to total body surface area of burn in patients (P &= .038). Musclin expression was significantly positively correlated with IL-4, IL-7, IL-12, and IL-13 in burn patients’ serum (P < .05). In the animal study, we found that the musclin level evaluated at 6 hours and 1 day in burn rat serum (P < .05). In vitro, musclin mRNA expression significantly increased with burn serum stimulation at 24 hours (P < .05). In conclusion, serum level of musclin elevated both in human patients and burn animals; musclin was correlated with the severity of burn injury as well as with an elevated cytokine profile in patients; burn serum-stimulated musclin expression in vitro further identified the resource of musclin expression after burn.
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Glatz, Jan F. C., Joost J. F. P. Luiken, and Arend Bonen. "Membrane Fatty Acid Transporters as Regulators of Lipid Metabolism: Implications for Metabolic Disease." Physiological Reviews 90, no. 1 (January 2010): 367–417. http://dx.doi.org/10.1152/physrev.00003.2009.
Full textAbstract:
Long-chain fatty acids and lipids serve a wide variety of functions in mammalian homeostasis, particularly in the formation and dynamic properties of biological membranes and as fuels for energy production in tissues such as heart and skeletal muscle. On the other hand, long-chain fatty acid metabolites may exert toxic effects on cellular functions and cause cell injury. Therefore, fatty acid uptake into the cell and intracellular handling need to be carefully controlled. In the last few years, our knowledge of the regulation of cellular fatty acid uptake has dramatically increased. Notably, fatty acid uptake was found to occur by a mechanism that resembles that of cellular glucose uptake. Thus, following an acute stimulus, particularly insulin or muscle contraction, specific fatty acid transporters translocate from intracellular stores to the plasma membrane to facilitate fatty acid uptake, just as these same stimuli recruit glucose transporters to increase glucose uptake. This regulatory mechanism is important to clear lipids from the circulation postprandially and to rapidly facilitate substrate provision when the metabolic demands of heart and muscle are increased by contractile activity. Studies in both humans and animal models have implicated fatty acid transporters in the pathogenesis of diseases such as the progression of obesity to insulin resistance and type 2 diabetes. As a result, membrane fatty acid transporters are now being regarded as a promising therapeutic target to redirect lipid fluxes in the body in an organ-specific fashion.
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Han, Seung Yeop, Ashutosh Pandey, Tereza Moore, Antonio Galeone, Lita Duraine, Tina M. Cowan, and Hamed Jafar-Nejad. "A conserved role for AMP-activated protein kinase in NGLY1 deficiency." PLOS Genetics 16, no. 12 (December 14, 2020): e1009258. http://dx.doi.org/10.1371/journal.pgen.1009258.
Full textAbstract:
Mutations in human N-glycanase 1 (NGLY1) cause the first known congenital disorder of deglycosylation (CDDG). Patients with this rare disease, which is also known as NGLY1 deficiency, exhibit global developmental delay and other phenotypes including neuropathy, movement disorder, and constipation. NGLY1 is known to regulate proteasomal and mitophagy gene expression through activation of a transcription factor called "nuclear factor erythroid 2-like 1" (NFE2L1). Loss of NGLY1 has also been shown to impair energy metabolism, but the molecular basis for this phenotype and its in vivo consequences are not well understood. Using a combination of genetic studies, imaging, and biochemical assays, here we report that loss of NGLY1 in the visceral muscle of the Drosophila larval intestine results in a severe reduction in the level of AMP-activated protein kinase α (AMPKα), leading to energy metabolism defects, impaired gut peristalsis, failure to empty the gut, and animal lethality. Ngly1–/– mouse embryonic fibroblasts and NGLY1 deficiency patient fibroblasts also show reduced AMPKα levels. Moreover, pharmacological activation of AMPK signaling significantly suppressed the energy metabolism defects in these cells. Importantly, the reduced AMPKα level and impaired energy metabolism observed in NGLY1 deficiency models are not caused by the loss of NFE2L1 activity. Taken together, these observations identify reduced AMPK signaling as a conserved mediator of energy metabolism defects in NGLY1 deficiency and suggest AMPK signaling as a therapeutic target in this disease.
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Camerino, Claudia. "Oxytocin Involvement in Body Composition Unveils the True Identity of Oxytocin." International Journal of Molecular Sciences 22, no. 12 (June 15, 2021): 6383. http://dx.doi.org/10.3390/ijms22126383.
Full textAbstract:
The origin of the Oxytocin/Vasopressin system dates back about 600 million years. Oxytocin (Oxt) together with Vasopressin (VP) regulate a diversity of physiological functions that are important for osmoregulation, reproduction, metabolism, and social behavior. Oxt/VP-like peptides have been identified in several invertebrate species and they are functionally related across the entire animal kingdom. Functional conservation enables future exploitation of invertebrate models to study Oxt’s functions not related to pregnancy and the basic mechanisms of central Oxt/VP signaling. Specifically, Oxt is well known for its effects on uteri contractility and milk ejection as well as on metabolism and energy homeostasis. Moreover, the striking evidence that Oxt is linked to energy regulation is that Oxt- and Oxytocin receptor (Oxtr)-deficient mice show late onset obesity. Interestingly Oxt−/− or Oxtr−/− mice develop weight gain without increasing food intake, suggesting that a lack of Oxt reduce metabolic rate. Oxt is expressed in a diversity of skeletal muscle phenotypes and regulates thermogenesis and bone mass. Oxt may increases skeletal muscle tonicity and/or increases body temperature. In this review, the author compared the three most recent theories on the effects of Oxt on body composition.
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Charron, Maureen J., and Patricia M. Vuguin. "Lack of glucagon receptor signaling and its implications beyond glucose homeostasis." Journal of Endocrinology 224, no. 3 (January 7, 2015): R123—R130. http://dx.doi.org/10.1530/joe-14-0614.
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Glucagon action is transduced by a G protein-coupled receptor located in liver, kidney, intestinal smooth muscle, brain, adipose tissue, heart, pancreatic β-cells, and placenta. Genetically modified animal models have provided important clues about the role of glucagon and its receptor (Gcgr) beyond glucose control. The PubMed database was searched for articles published between 1995 and 2014 using the key terms glucagon, glucagon receptor, signaling, and animal models. Lack of Gcgr signaling has been associated with: i) hypoglycemic pregnancies, altered placentation, poor fetal growth, and increased fetal–neonatal death; ii) pancreatic glucagon cell hyperplasia and hyperglucagonemia; iii) altered body composition, energy state, and protection from diet-induced obesity; iv) impaired hepatocyte survival; v) altered glucose, lipid, and hormonal milieu; vi) altered metabolic response to prolonged fasting and exercise; vii) reduced gastric emptying and increased intestinal length; viii) altered retinal function; and ix) prevention of the development of diabetes in insulin-deficient mice. Similar phenotypic findings were observed in the hepatocyte-specific deletion ofGcgr. Glucagon action has been involved in the modulation of sweet taste responsiveness, inotropic and chronotropic effects in the heart, satiety, glomerular filtration rate, secretion of insulin, cortisol, ghrelin, GH, glucagon, and somatostatin, and hypothalamic signaling to suppress hepatic glucose production. Glucagon (α) cells under certain conditions can transdifferentiate into insulin (β) cells. These findings suggest that glucagon signaling plays an important role in multiple organs. Thus, treatment options designed to block Gcgr activation in diabetics may have implications beyond glucose homeostasis.
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Coba, MP, MC Munoz, FP Dominici, JE Toblli, C. Pena, A. Bartke, and D. Turyn. "Increased in vivo phosphorylation of insulin receptor at serine 994 in the liver of obese insulin-resistant Zucker rats." Journal of Endocrinology 182, no. 3 (September 1, 2004): 433–44. http://dx.doi.org/10.1677/joe.0.1820433.
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Serine phosphorylation of the insulin receptor (IR) has been proposed to exert an inhibitory influence on its tyrosine kinase activity. Previous works using site-directed mutagenesis suggested that serine 994 of the IR (IR Ser 994) might be part of an inhibitory domain of the receptor. In this study we examined whether this residue is subjected to phosphorylation in vivo. We used a site-phosphospecific antibody to determine the extent of phosphorylation of IR Ser 994 in insulin target tissues from two animal models of insulin resistance with different IR kinase (IRK) activity: obese (fa/fa) Zucker rats and transgenic mice overexpressing bovine growth hormone (PEPCK-bGH mice).Phosphorylation at IR Ser 994 was markedly increased in liver of obese rats. This alteration appeared to be tissue-selective since no phosphorylation on Ser 994 was detected in IRs isolated from skeletal muscle of these animals. On the other hand, the phosphorylation level of IR Ser 994 was very low in liver of PEPCK-bGH mice and did not differ from that of the control group. We have also demonstrated that protein kinase (PK) C isoforms alpha, betaI and zeta are able to promote the in vitro phosphorylation of the IR on Ser 994. Differential findings in these two models of insulin resistance might thus reflect increased PKC activity resulting from increased lipid availability in obese Zucker rats. Our results suggest that Ser 994 is a novel in vivo IR phosphorylation site that might be involved in the regulation of the IRK in some states of insulin resistance.
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Post, Wilke M., Joanna Widomska, Hilde Grens, Marieke J. H. Coenen, Frank M. J. Martens, Dick A. W. Janssen, Joanna IntHout, Geert Poelmans, Egbert Oosterwijk, and Kirsten B. Kluivers. "Molecular Processes in Stress Urinary Incontinence: A Systematic Review of Human and Animal Studies." International Journal of Molecular Sciences 23, no. 6 (March 21, 2022): 3401. http://dx.doi.org/10.3390/ijms23063401.
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Stress urinary incontinence (SUI) is a common and burdensome condition. Because of the large knowledge gap around the molecular processes involved in its pathophysiology, the aim of this review was to provide a systematic overview of genetic variants, gene and protein expression changes related to SUI in human and animal studies. On 5 January 2021, a systematic search was performed in Pubmed, Embase, Web of Science, and the Cochrane library. The screening process and quality assessment were performed in duplicate, using predefined inclusion criteria and different quality assessment tools for human and animal studies respectively. The extracted data were grouped in themes per outcome measure, according to their functions in cellular processes, and synthesized in a narrative review. Finally, 107 studies were included, of which 35 used animal models (rats and mice). Resulting from the most examined processes, the evidence suggests that SUI is associated with altered extracellular matrix metabolism, estrogen receptors, oxidative stress, apoptosis, inflammation, neurodegenerative processes, and muscle cell differentiation and contractility. Due to heterogeneity in the studies (e.g., in examined tissues), the precise contribution of the associated genes and proteins in relation to SUI pathophysiology remained unclear. Future research should focus on possible contributors to these alterations.
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Yokoyama, Yoko, Kawori Shinohara, Naho Kitamura, Anna Nakamura, Ai Onoue, Kazuki Tanaka, Akiyoshi Hirayama, et al. "Metabolic Effects of Bee Larva-Derived Protein in Mice: Assessment of an Alternative Protein Source." Foods 10, no. 11 (November 1, 2021): 2642. http://dx.doi.org/10.3390/foods10112642.
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Food crises caused by growing global population or environmental changes are predicted in the near future; therefore, sustainable solutions are needed. Edible insects, which are rich in protein and can save feed and environmental resources, have the potential to be a sustainable alternative protein source. However, there is limited evidence on the impact on health. In this study, we investigated the biological effects of ingesting bee larva by examining their effects on amino acid, lipid, and glucose metabolism in animal models. In our animal experiments, the replacement of casein as a protein source, with edible insects, did not seem to cause any deficiency in murine amino acid levels in the plasma and liver. Metabolomic analysis of plasma metabolites showed decreased 3-methylhistidine and increased nicotinamide in the bee larva-derived protein-fed mice. Decreased levels of plasma 3-metylhistidine, an indicator of muscle degradation, implies that replacement to bee-larva protein from casein did not cause muscle degradation in vivo. We further investigated effects of increased plasma nicotinamide on peripheral tissue and found an increase in expression levels of genes involved in glucose uptake in muscle and thermogenesis in adipose tissue. These data imply that bee larva is a potential sustainable, safe and healthy alternative protein source.