Relevant bibliographies by topics / FFA2

Academic literature on the topic 'FFA2'

Author: Grafiati
Published: 10 December 2022
Last updated: 28 January 2023

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Journal articles on the topic "FFA2"

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Priyadarshini, Medha, Guadalupe Navarro, and Brian T. Layden. "Gut Microbiota: FFAR Reaching Effects on Islets." Endocrinology 159, no. 6 (May 4, 2018): 2495–505. http://dx.doi.org/10.1210/en.2018-00296.

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Abstract The G protein–coupled receptors, free fatty acid (FFA) receptors 2 and 3 (FFA2 and FFA3), belonging to the free fatty acid receptor (FFAR) class, sense a distinct class of nutrients, short chain fatty acids (SCFAs). These receptors participate in both immune and metabolic regulation. The latter includes a role in regulating secretion of metabolic hormones. It was only recently that their role in pancreatic β cells was recognized; these receptors are known now to affect not only insulin secretion but also β-cell survival and proliferation. These observations make them excellent potential therapeutic targets in type 2 diabetes. Moreover, expression on both immune and β cells makes these receptors possible targets in type 1 diabetes. Furthermore, SCFAs are generated by gut microbial fermentative activity; therefore, signaling by FFA2 and FFA3 represents an exciting novel link between the gut microbiota and the β cells. This review enumerates the role of these receptors in β cells revealed so far and discusses possible roles in clinical translation.
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Schmidt, Johannes, Nicola J. Smith, Elisabeth Christiansen, Irina G. Tikhonova, Manuel Grundmann, Brian D. Hudson, Richard J. Ward, et al. "Selective Orthosteric Free Fatty Acid Receptor 2 (FFA2) Agonists." Journal of Biological Chemistry 286, no. 12 (January 10, 2011): 10628–40. http://dx.doi.org/10.1074/jbc.m110.210872.

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Free fatty acid receptor 2 (FFA2; GPR43) is a G protein-coupled seven-transmembrane receptor for short-chain fatty acids (SCFAs) that is implicated in inflammatory and metabolic disorders. The SCFA propionate has close to optimal ligand efficiency for FFA2 and can hence be considered as highly potent given its size. Propionate, however, does not discriminate between FFA2 and the closely related receptor FFA3 (GPR41). To identify FFA2-selective ligands and understand the molecular basis for FFA2 selectivity, a targeted library of small carboxylic acids was examined using holistic, label-free dynamic mass redistribution technology for primary screening and the receptor-proximal G protein [35S]guanosine 5′-(3-O-thio)triphosphate activation, inositol phosphate, and cAMP accumulation assays for hit confirmation. Structure-activity relationship analysis allowed formulation of a general rule to predict selectivity for small carboxylic acids at the orthosteric binding site where ligands with substituted sp3-hybridized α-carbons preferentially activate FFA3, whereas ligands with sp2- or sp-hybridized α-carbons prefer FFA2. The orthosteric binding mode was verified by site-directed mutagenesis: replacement of orthosteric site arginine residues by alanine in FFA2 prevented ligand binding, and molecular modeling predicted the detailed mode of binding. Based on this, selective mutation of three residues to their non-conserved counterparts in FFA3 was sufficient to transfer FFA3 selectivity to FFA2. Thus, selective activation of FFA2 via the orthosteric site is achievable with rather small ligands, a finding with significant implications for the rational design of therapeutic compounds selectively targeting the SCFA receptors.
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Gough, Sophie, Brian Layden, Chioma Nnyamah, Medha Priyadarshini, Barton Wicksteed, and Kristen Lednovich. "OR23-4 Intestinal FFA2 and FFA3 Mediate Obesogenic Effects in Mice on a Western Diet." Journal of the Endocrine Society 6, Supplement_1 (November 1, 2022): A19. http://dx.doi.org/10.1210/jendso/bvac150.040.

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Abstract Free fatty acid receptor 2 and free fatty acid receptor 3 (FFA2/3) are two highly similar G protein-coupled receptors belonging to the free fatty acid receptor family. Their ligands are short-chain fatty acids (SCFAs), which are key nutrients that play a diverse role in physiological function, including the regulation of metabolic homeostasis and glycemic control. FFA2/3 are broadly expressed in a multitude of tissues including the intestine, pancreas, adipose and central nervous system, where they contribute to metabolic homeostasis via a summation of tissue-specific effects. Consequently, FFA2/3 have been identified as a potential drug target for metabolic diseases including obesity and type-2 diabetes. Both FFA2 and FFA3 are highly expressed within the intestinal epithelium – the major site of SCFA generation – and have been identified in hormone-secreting enteroendocrine cells as well as intestinal epithelial cells. However, due conflicting data, the respective roles of FFA2/3 within the intestine and their effects on physiology and metabolism are still largely unclear. Previous in vivo studies involving this receptor have largely relied on global knockout mouse models, making it difficult to isolate their effects in the intestine. To overcome this challenge, we generated a novel intestine-specific knockout mouse model for FFA2 and FFA3 individually, utilizing Cre-mediated recombination under the expression of the villin promoter. Here, we report the first in vivo characterization of FFA2/3 in the intestine and reveal novel insights into receptor function. Following model validation, we conducted a general metabolic assessment of male Villin-Cre-FFA2 (Vil-FFA2) and Villin-Cre-FFA3 (Vil-FFA3) mice on standard chow and observed no major congenital or time-dependent defects. Because dietary changes are known to alter gut microbial composition, and thereby SCFA production, a pilot study was performed on male Vil-FFA2 and Vil-FFA3 mice and their littermate controls to probe for a phenotype on a high-fat, high-sugar "western diet." Mice were placed on either a low-fat control diet (CD) or western diet (WD) at 10 weeks of age and metabolically profiled for 25 weeks. We found that both Vil-FFA2 and Vil-FFA3 mouse strains were largely protected from diet-induced obesity and had significantly lower fat mass as well as adipose hypertrophy. Additionally, both mouse strains had reduced intestinal inflammation and improved glucose homeostasis. These differences were driven by lower food intake in the Vil-FFA2 strain only. Our findings suggest a novel role of FFA2/3 in mediating the metabolic consequences of a western diet – a state of high inflammation, dysbiosis and metabolic stress. Moreover, these data support an intestine-specific role of FFA2/3 in whole-body metabolic homeostasis and in the development of adiposity and hyperglycemia. Presentation: Monday, June 13, 2022 12:00 p.m. - 12:15 p.m.
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Villa, Stephanie R., Rama K. Mishra, Joseph L. Zapater, Medha Priyadarshini, Annette Gilchrist, Helena Mancebo, Gary E. Schiltz, and Brian T. Layden. "Homology modeling of FFA2 identifies novel agonists that potentiate insulin secretion." Journal of Investigative Medicine 65, no. 8 (August 7, 2017): 1116–24. http://dx.doi.org/10.1136/jim-2017-000523.

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Critical aspects of maintaining glucose homeostasis in the face of chronic insulin resistance and type 2 diabetes (T2D) are increased insulin secretion and adaptive expansion of beta cell mass. Nutrient and hormone sensing G protein-coupled receptors are important mediators of these properties. A growing body of evidence now suggests that the G protein-coupled receptor, free fatty acid receptor 2 (FFA2), is capable of contributing to the maintenance of glucose homeostasis by acting at the pancreatic beta cell as well as at other metabolically active tissues. We have previously demonstrated that Gαq/11-biased agonism of FFA2 can potentiate glucose stimulated insulin secretion (GSIS) as well as promote beta cell proliferation. However, the currently available Gαq/11-biased agonists for FFA2 exhibit low potency, making them difficult to examine in vivo. This study sought to identify Gαq/11-biased FFA2-selective agonists with potent GSIS-stimulating effects. To do this, we generated an FFA2 homology model that was used to screen a library of 10 million drug-like compounds. Although FFA2 and the related short chain fatty acid receptor FFA3 share 52% sequence similarity, our virtual screen identified over 50 compounds with predicted selectivity and increased potency for FFA2 over FFA3. Subsequent in vitro calcium mobilization assays and GSIS assays resulted in the identification of a compound that can potentiate GSIS via activation of Gαq/11with 100-fold increased potency compared with previously described Gαq/11-biased FFA2 agonists. These methods and findings provide a foundation for future discovery efforts to identify biased FFA2 agonists as potential T2D therapeutics.
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Bisenieks, Egils, Brigita Vigante, Ramona Petrovska, Baiba Turovska, Ruslan Muhamadejev, Vitalijs Soloduns, Astrida Velena, et al. "The Specificity and Broad Multitarget Properties of Ligands for the Free Fatty Acid Receptors FFA3/GPR41 and FFA2/GPR43 and the Related Hydroxycarboxylic Acid Receptor HCA2/GPR109A." Pharmaceuticals 14, no. 10 (September 28, 2021): 987. http://dx.doi.org/10.3390/ph14100987.

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The paradigm of ligand-receptor interactions postulated as “one compound—one target” has been evolving; a multi-target, pleiotropic approach is now considered to be realistic. Novel series of 1,4,5,6,7,8-hexahydro-5-oxoquinolines, pyranopyrimidines and S-alkyl derivatives of pyranopyrimidines have been synthesized in order to characterise their pleiotropic, multitarget activity on the FFA3/GPR41, FFA2/GPR43, and HCA2/GPR109A receptors. Hexahydroquinoline derivatives have been known to exhibit characteristic activity as FFA3/GPR41 ligands, but during this study we observed their impact on FFA2/GPR43 and HCA2/GPR109A receptors as well as their electron-donating activity. Oxopyranopyrimidine and thioxopyranopyrimidine type compounds have been studied as ligands of the HCA2/GPR109A receptor; nevertheless, they exhibited equal or higher activity towards FFA3/GPR41 and FFA2/GPR43 receptors. S-Alkyl derivatives of pyranopyrimidines that have not yet been studied as ligands of GPCRs were more active towards HCA2/GPR109A and FFA3/GPR41 receptors than towards FFA2/GPR43. Representative compounds from each synthesized series were able to decrease the lipopolysaccharide-induced gene expression and secretion of proinflammatory cytokines (IL-6, TNF-α) and of a chemokine (MCP-1) in THP-1 macrophages, resembling the effect of HCA2/GPR109A ligand niacin and the endogenous ligand propionate. This study revealed groups of compounds possessing multitarget activity towards several receptors. The obtained data could be useful for further development of multitarget ligands.
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Nnyamah, Christine, Barton Wicksteed, and Brian Layden. "PSUN82 The Gut Microbiome Regulates Healthy Adipose Tissue Expansion via the Action of FFA2." Journal of the Endocrine Society 6, Supplement_1 (November 1, 2022): A25. http://dx.doi.org/10.1210/jendso/bvac150.053.

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Abstract The obesity pandemic is a major health concern driving Type 2 Diabetes (T2D) and cardiovascular disease (CVD). One novel pathogenetic factor of obesity is the gut microbiome (GM), that is the microbes that reside in the digestive tract. Changes in the GM have profound effects on the obesity. These symbiotic microbes break down dietary fiber that are otherwise indigestible, releasing nutrients (in particular, short chain fatty acids, SCFAs). Free Fatty Acid Receptor 2 (FFA2) is a G-protein coupled receptor (GPCR) that senses SCFAs and influences secretion of the appetite-regulating proteins GLP-1 and PYY from enteroendocrine cells. However, its role in adipose tissue is less clear. While highly expressed in adipose tissue, research using global knockouts (KOs) of FFA2 in mouse models has observed conflicting phenotypic results. Here, we use adipocytes isolated from FFA2-KO and WT mice and SCFA-supplemented media to demonstrate that acetate, a primary ligand of FFA2, leads to increased adipogenesis. This expansion of total adipocyte population rather than individual size has been shown to greatly decrease metabolic health complications in highly obese individuals. Our ongoing research aims to explore the in vitro effects of FFA2 on lipogenesis, lipolysis, and secretion of adipokines. Primarily, we are exploring these outcomes in vivo using novel adipose-specific FFA2 KO (AdFFA2-KO) mice which we show have no congenital defects and are metabolically similar to FFA2 floxxed control mice on a normal chow diet. Our ongoing research challenges the mice with obesogenic diets to observe the effects of metabolic strain on FFA2 function specifically in adipose tissue. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
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Zhang, J., S. Cheng, Y. Wang, X. Yu, and J. Li. "Identification and characterization of the free fatty acid receptor 2 (FFA2) and a novel functional FFA2-like receptor (FFA2L) for short-chain fatty acids in pigs: Evidence for the existence of a duplicated FFA2 gene (FFA2L) in some mammalian species." Domestic Animal Endocrinology 47 (April 2014): 108–18. http://dx.doi.org/10.1016/j.domaniend.2013.10.004.

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Fuller, Miles, Medha Priyadarshini, Sean M. Gibbons, Anthony R. Angueira, Michael Brodsky, M. Geoffrey Hayes, Petia Kovatcheva-Datchary, et al. "The short-chain fatty acid receptor, FFA2, contributes to gestational glucose homeostasis." American Journal of Physiology-Endocrinology and Metabolism 309, no. 10 (November 15, 2015): E840—E851. http://dx.doi.org/10.1152/ajpendo.00171.2015.

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The structure of the human gastrointestinal microbiota can change during pregnancy, which may influence gestational metabolism; however, a mechanism of action remains unclear. Here we observed that in wild-type (WT) mice the relative abundance of Actinobacteria and Bacteroidetes increased during pregnancy. Along with these changes, short-chain fatty acids (SCFAs), which are mainly produced through gut microbiota fermentation, significantly changed in both the cecum and peripheral blood throughout gestation in these mice. SCFAs are recognized by G protein-coupled receptors (GPCRs) such as free fatty acid receptor-2 (FFA2), and we have previously demonstrated that the fatty acid receptor-2 gene ( Ffar2) expression is higher in pancreatic islets during pregnancy. Using female Ffar2−/− mice, we explored the physiological relevance of signaling through this GPCR and found that Ffar2-deficient female mice developed fasting hyperglycemia and impaired glucose tolerance in the setting of impaired insulin secretion compared with WT mice during, but not before, pregnancy. Insulin tolerance tests were similar in Ffar2−/− and WT mice before and during pregnancy. Next, we examined the role of FFA2 in gestational β-cell mass, observing that Ffar2−/− mice had diminished gestational expansion of β-cells during pregnancy. Interestingly, mouse genotype had no significant impact on the composition of the gut microbiome, but did affect the observed SCFA profiles, suggesting a functional difference in the microbiota. Together, these results suggest a potential link between increased Ffar2 expression in islets and the alteration of circulating SCFA levels, possibly explaining how changes in the gut microbiome contribute to gestational glucose homeostasis.
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Lednovlch, Kristen R., Sophie Gough, Medha Priyadarshini, and Brian Layden. "Tu1952 DEFINING THE ROLE OF INTESTINE-SPECIFIC FFA2 AND FFA3 IN HORMONAL SECRETION." Gastroenterology 158, no. 6 (May 2020): S—1231. http://dx.doi.org/10.1016/s0016-5085(20)33739-2.

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Kaji, Izumi, Yasutada Akiba, Jonathan D. Kaunitz, Shin-ichiro Karaki, and Atsukazu Kuwahara. "Su1745 Differential Expression of Short-Chain Fatty Acid Receptor FFA2 and FFA3 in Foregut." Gastroenterology 142, no. 5 (May 2012): S—494. http://dx.doi.org/10.1016/s0016-5085(12)61887-3.

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Dissertations / Theses on the topic "FFA2"

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Lamodière, Elisabeth. "Nouveaux concepts dans la pharmacologie des récepteurs aux acides gras à chaîne courte FFA2 et FFA3." Phd thesis, Université de Bourgogne, 2011. http://tel.archives-ouvertes.fr/tel-00668234.

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Les maladies métaboliques, comme le diabète, la dyslipidémie ou l'obésité, constituent un problème majeur de santé publique dans les pays développés. Ces maladies très répandues restent encore difficiles à traiter malgré une recherche active. Les stratégies thérapeutiques contre ces maladies incluent le développement de nouvelles molécules ciblant les récepteurs aux acides gras, étant donné leur rôle essentiel dans l'homéostasie du métabolisme. C'est dans ce contexte que s'inscrit ce travail portant sur deux récepteurs couplés aux protéines G, les récepteurs aux acides gras à courte chaîne 2 et 3 ou free fatty acid receptors 2 (FFA2) et 3 (FFA3). Nous avons tout d'abord cherché à déterminer le profil d'expression des deux récepteurs. Ensuite, nous avons établi des lignées cellulaires stable exprimant FFA2 ou FFA3 afin d'étudier la pharmacologie d'agonistes synthétiques et endogènes de ces récepteurs. Après avoir identifié les voies de signalisation engendrées par l'activation des récepteurs, nous avons démontré que les agonistes synthétiques étaient des activateurs allostériques, c'est-à-dire qu'ils se liaient aux récepteurs sur un site distinct de celui des ligands endogènes. Pour identifier les résidus d'acides aminés nécessaires à la reconnaissance des ligands, nous avons généré une gamme de mutants ponctuels de ces récepteurs par mutagénèse dirigée. En analysant l'effet des mutations dans des tests fonctionnels, nous avons pu déterminer avec précision où se liaient les ligands et ainsi pu dessiner par informatique des modèles structuraux des récepteurs qui pourront être utilisés pour le drug design de futures molécules agonistes de ces récepteurs.
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Moussaud, Elisabeth. "Nouveaux concepts dans la pharmacologie des récepteurs aux acides gras à chaîne courte FFA2 et FFA3." Thesis, Dijon, 2011. http://www.theses.fr/2011DIJOS014/document.

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Les maladies métaboliques, comme le diabète, la dyslipidémie ou l’obésité, constituent un problème majeur de santé publique dans les pays développés. Ces maladies très répandues restent encore difficiles à traiter malgré une recherche active. Les stratégies thérapeutiques contre ces maladies incluent le développement de nouvelles molécules ciblant les récepteurs aux acides gras, étant donné leur rôle essentiel dans l’homéostasie du métabolisme. C’est dans ce contexte que s’inscrit ce travail portant sur deux récepteurs couplés aux protéines G, les récepteurs aux acides gras à courte chaîne 2 et 3 ou free fatty acid receptors 2 (FFA2) et 3 (FFA3). Nous avons tout d'abord cherché à déterminer le profil d'expression des deux récepteurs. Ensuite, nous avons établi des lignées cellulaires stable exprimant FFA2 ou FFA3 afin d’étudier la pharmacologie d’agonistes synthétiques et endogènes de ces récepteurs. Après avoir identifié les voies de signalisation engendrées par l’activation des récepteurs, nous avons démontré que les agonistes synthétiques étaient des activateurs allostériques, c’est-à-dire qu’ils se liaient aux récepteurs sur un site distinct de celui des ligands endogènes. Pour identifier les résidus d’acides aminés nécessaires à la reconnaissance des ligands, nous avons généré une gamme de mutants ponctuels de ces récepteurs par mutagénèse dirigée. En analysant l’effet des mutations dans des tests fonctionnels, nous avons pu déterminer avec précision où se liaient les ligands et ainsi pu dessiner par informatique des modèles structuraux des récepteurs qui pourront être utilisés pour le drug design de futures molécules agonistes de ces récepteurs
Metabolic diseases, such as diabetes, dyslipidemia or obesity, are more and more weighing on public health expenses in developed countries. Despite active research, these widespread diseases remain difficult to handle. Promising new therapeutic strategies against metabolic diseases include the development of drugs targeting the free fatty acid receptors, as key players in metabolism homeostasis. In this context, the current PhD thesis focuses on the study of two G protein-coupled receptors, namely the short-chain free fatty acid receptors 2 (FFA2) and 3 (FFA3). First, we investigated the expression of the two receptors of interest in a variety of cell types. Then, in order to study the pharmacology and the binding mode of endogenous and synthetic agonists on FFA2 and FFA3, we established stable cell lines expressing each receptor. Once we identified the signaling pathways engendered in response to receptor activation, we showed that synthetic agonists were allosteric activators of the receptors, in the sense that they bind to the receptors at a distinct site from short-chain fatty acids, i.e. the endogenous agonists. To identify the aminoacid residues that were involved in ligand binding, we generated a variety of point mutated receptors by site-directed mutagenesis. By analyzing the effects of the mutations in functional tests, we determined precisely the aminoacid residues that were essential for ligand binding. From these results, we designed in silico structural models which may aid future drug design efforts for the discovery of new FFA2 and FFA3 agonists
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Sergeev, Eugenia. "Investigating the molecular pharmacology of the short chain fatty acid receptor FFA2." Thesis, University of Glasgow, 2018. http://theses.gla.ac.uk/8963/.

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The G protein-coupled receptor FFA2 is a key mediator of short chain fatty acid signalling, which are produced in the gut via fermentation of poorly digested carbohydrates by the gut microbiota. Therefore, FFA2 has attracted interest as a potential therapeutic target for metabolic and inflammatory diseases. However, several limitations have hindered validation of FFA2 as a drug target, including the limited understanding of the molecular determinants of ligand binding and species-specific differences in pharmacology. Herein, novel tool compounds and assay systems were developed for FFA2 and utilised to address some of these limitations. Following the characterisation of functional assays for detection of FFA2 signalling, these were employed to examine the structure-activity relationship and pharmacology of FFA2 agonists versus antagonists. To assess how the pharmacology of FFA2 ligands is defined by their mode of binding, a radioligand binding assay was developed using a tritiated form of FFA2 antagonist GLPG0974 that was utilised in combination with site-directed mutagenesis and homology modelling to explore FFA2 ligand binding sites. These studies showed that FFA2 agonist binding was defined by an essential interaction between the ligand carboxylate and an orthosteric Arg-His-Arg triad. In contrast, FFA2 antagonists only required one orthosteric arginine for high-affinity binding and could tolerate modifications of the carboxylate moiety. This knowledge was applied to develop an antagonist-based fluorescent tracer for FFA2 that was utilised in BRET binding assays but displayed complex pharmacological behaviour that was shown to be based on the bitopic nature of FFA2 antagonists. The secondary binding site of FFA2 antagonists was also related to their lack of action at rodent orthologues of FFA2, whose molecular basis was explored using homology models of human and murine FFA2. This facilitated the identification of a single lysine to arginine variation at position 2.60 that might provide a basis for antagonist selectivity. Extending these studies to agonist function demonstrated that removal of the positive charge at this position produced a signalling-biased form of FFA2, in which only coupling to Gi G proteins was fully maintained. In summary, these findings contribute to understanding the complex pharmacology of FFA2 ligands and the underlying mechanisms that define their function, and conclusions drawn from these studies may help advance future efforts to validate the therapeutic potential of targeting FFA2.
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Raihan, Sheikh Zahir. "Desensitisation of the human long chain fatty acid receptors FFA1 and FFA4." Thesis, University of Glasgow, 2017. http://theses.gla.ac.uk/8144/.

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G protein-coupled receptors (GPCRs) constitute the largest, most ubiquitous and most versatile family of membrane proteins encoded by the human genome. Due to diverse ligands and multiple physiological activities, this set of receptors has frequently been explored as potential drug targets. Deorphanisation of GPCRs successfully identified FFA1 and FFA4 (previously named GPR40 and GPR120) as long chain free fatty acid receptors. With diverse expression patterns and close association to pathophysiology of metabolic diseases, both receptors are being studied to understand both receptor pharmacology and their potential for drug development. Due to the overlap in the activation of FFA1 and FFA4 by endogenous fatty acid ligands, selective synthetic ligands have been developed for these receptors. Using a number of biochemical and biophysical assays, I have characterised TUG-770, TUG-905 and GW-1100 as FFA1 ligands and TUG-891, TUG-1197 and TUG-1275 as FFA4 ligands. TUG-905 was found to be most potent and selective FFA1 agonist and GW-1100 showed insurmountable antagonism at FFA1. At FFA4, TUG-1197 was found to be a highly potent and selective agonist. TUG-1275 showed insurmountable antagonism at FFA4 in β-arrestin2 recruitment, receptor internalisation and inositol monophosphate accumulation studies and showed complete selectivity for hFFA4. Agonist exposure rapidly phosphorylated FFA4 in an agonist-concentration-dependent fashion which was totally blocked by TUG-1275. The protein kinase C activator PMA was also noted to phosphorylate FFAA in a concentration-dependent manner. Thus both homologous and heterologous phosphorylation is involved in FFA4 regulation. The FFA4-agonist TUG-891 produced robust internalisation of FFA4 as detected by each of confocal microscopy, and both cell surface ELISA and biotinylation. PMA was able to internalise FFA4 although it was unable to recruit β-arrestin2 to FFA4 suggesting that this internalisation might not be β-arrestin2-dependent. Constitutive internalisation was seen for FFA1, where the selective FFA1 antagonist GW-1100 had no effect. Repeated agonist-exposure desensitised both FFA1 and FF4 as revealed in single-cell calcium imaging studies. Although there was a small reduction of FFA4-internalisation and a slight elevation of total calcium levels from a single-chronic exposure of agonist, elimination of β-arrestin1/2 from HEK293 cells by genome editing did not significantly change the desensitisation of FFA4 to repeated exposure of agonist and did not prevent agonist-promoted internalisation. These studies indicate that β-arrestins are not the sole factors in desensitisation of human FFA4. Gαq/11 elimination by genome editing completely blocked intracellular calcium mobilisation and accumulation of inositol monophosphates mediated by both FFA1 and FFA4 indicating that Gαq/11 coupling to agonist-activated receptors is essential for this functional signalling outcome via both receptors. FFA4 expressed in Gαq/11-null cells was found to be phosphorylated by agonist, indicating that phosphorylation-mediated desensitisation of this receptor is not dependent on Gαq/11 proteins. FRET and BRET experiments revealed for the first time homo and hetero-oligomerisation of both FFA1 and FFA4. Although ligand regulation of oligomerisation was not investigated these preliminary observations of oligomerisation may help in the future to answer many questions of regulation and desensitisation of these receptors. The selective FFA1 and FFA4 ligands characterised here in this project might be used as tool compounds to further explore the physiology and pharmacology of these therapeutically important receptors.
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Josefsson, Ragnar, and Joel Storm. "Materialförsörjning hos FFAB." Thesis, Linköpings universitet, Kommunikations- och transportsystem, 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-151067.

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Denna rapport är en fallstudie som har gjorts på det båttillverkande företaget FFAB. FFAB har svårigheter att styra materialflödet, från varumottag till montering, på ett standardiserat och förutsägbart vis. Som en följd av detta har montörerna svårt att hitta alla komponenter de behöver vilket spiller tid från själva monteringsarbetet. Syftet med fallstudien har således varit att klargöra materialförsörjningen till en av FFABs produktionslinor och ge förbättringsförslag för att reducera andelen icke-värdeskapande aktiviteter kopplat till produktionsprocessen. Fallstudien fann fem grundorsaker till icke-värdeskapande aktiviteter; oreda, materialpresentationen, monteringsstrukturen, informationssystemet och kittningen. Åtgärderna till de rådande problemen och därmed vår slutsats blev att införa 5S för att få bukt på den oreda som finns vid samtliga lagerpunkter, att standardisera kittningen och systematiken på materialfasaderna och att i större utsträckning involvera montörerna i planeringsarbetet.
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LAGRANGE, Jean-Baptiste Henri Raymond. "Study of zero-chromaticity in FFAG accelerators." 京都大学 (Kyoto University), 2012. http://hdl.handle.net/2433/157577.

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Vanderbos, Sara. "Factors that influence secondary students to join the Collegiate FFA." DigitalCommons@USU, 2013. https://digitalcommons.usu.edu/etd/1489.

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Student involvement on college campuses is important for the professional growth, leadership development and learning of today's college student. This research sought to determine the factors that influence former high school FFA members' reasons for joining and participating in the Collegiate FFA. The study showed that students who are involved in the National FFA at the secondary level are more likely to join Collegiate FFA while attending a university that offers the Collegiate FFA option. These students were actively engaged on campus and were interested in helping others. Collegiate FFA programs, the National FFA, and universities across the country should begin their recruitment efforts with current high school FFA members.
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Yamakawa, Emi. "Study of serpentine acceleration in zero-chromatic FFAG accelerators." 京都大学 (Kyoto University), 2013. http://hdl.handle.net/2433/174929.

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PLANCHE, Thomas. "Study of zero-chromatic FFAG synchrotron for muon acceleration." 京都大学 (Kyoto University), 2010. http://hdl.handle.net/2433/131890.

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Bryant, Bradley Wayne. "History of the Virginia FFA Association." Diss., Virginia Tech, 2001. http://hdl.handle.net/10919/26640.

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Part of this research focused on the predecessors of the FFA by outlining the history and purposes of agricultural organizations formed since the late 1700s. The past two centuries of American agricultural history is rich with efforts to educate and improve agricultural practices through organized groups of farmers and other rural leaders. Early in the development of agricultural societies, experimentation and successful practices were shared with others in the local organization and works were often published in journals or newspapers for educational and informational purposes. Regular meetings and fellowship were also a major focus of the early groups. The national organizations that formed later such as the Grange, included the fraternal, social, and educational aspects while maintaining a focus on the economics of farming. The boys’ and girls’ club movement provided opportunities for youth to meet, learn, and participate in agricultural competitions. The center of activities for youth organizations quickly shifted from community groups to agricultural education programs in the public schools. Clubs that formed within agricultural education programs in Virginia soon united to create the Future Farmers of Virginia. The FFV and FFA that followed initiated the use of certain symbols, colors, and ritual ceremonies that can be traced directly to the agricultural societies. This research identified many agricultural societies and youth clubs that had a profound influence on the development of the National FFA Organization. The major purpose of this study was to describe the establishment of the Future Farmers of American and to document the accomplishments of Virginia FFA members at the state and national levels. The objectives of the study were: To describe the historical events and circumstances that led to the establishment of the Future Farmers of Virginia and the Future Farmers of America, To document Virginia FFA history by recording achievements of members and chapters at the state level, To document the achievements of Virginia FFA members and chapters at the national level, and To provide a history of the Virginia FFA Association from 1925 to the present. The Virginia FFA Association is rich with historical information that ranges from the formation of the Future Farmers of Virginia in 1925, the forming of a national organization in 1928, and 75 years of accomplishments by Virginia FFA members.
Ph. D.
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Books on the topic "FFA2"

1

Paul, Korky. Trysor Twm Ffat. Llandysul: Gomer, 1994.

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International, Workshop on FFAG Accelerators (13th 2007 Osaka Japan). The International Workshop on FFAG Accelerators. Ōsaka-fu, Sennan-gun, Kumatori-chō: Research Reactor Institute, Kyoto University, 2008.

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M, Lefèvre A., ed. Jac a'r goeden ffa. Llanrwst: Gwasg Carreg Gwalch, 2001.

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J, Petersilie Erin, and Future Farmers of America, eds. The FFA cookbook: Favorite recipes from FFA members and alumni across America. Minneapolis, Minn: MBI Pub. Company, 2009.

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Ayala, Julio Guillermo Meza. Derecho de pensiones en la PNP y FFAA. Perú: s.n., 2004.

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Rodrigo, Álvarez V., ed. ¿Construyendo confianza?: Fronteras, FFAA y política en América Latina. Santiago de Chile: FLACSO-CHILE, 2008.

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Razeto, Sebastián Briones. ¿Construyendo confianza?: Fronteras, FFAA y política en América Latina. Santiago de Chile: FLACSO-CHILE, 2008.

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Petty, Dustin. Michigan FFA: A legacy of Great Lakes leadership. Evansville, IN: M.T. Pub. Co., 2008.

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Hughes, A. V. FFA member country contributions: A revised formula : report. Port Vila, Vanuatu: United Nations, Economic and Social Commission for Asia and the Pacific, Pacific Operations Centre, 1996.

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Gillett, R. D. A Review of the FFA Regional Fishery Observer Programme. Manila, Philippines: Asian Development Bank, 2001.

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Book chapters on the topic "FFA2"

1

Tang, Cong, and Stefan Offermanns. "FFA2 and FFA3 in Metabolic Regulation." In Free Fatty Acid Receptors, 205–20. Cham: Springer International Publishing, 2016. http://dx.doi.org/10.1007/164_2016_50.

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Gribble, Fiona M., Eleftheria Diakogiannaki, and Frank Reimann. "Gut Hormone Regulation and Secretion via FFA1 and FFA4." In Free Fatty Acid Receptors, 181–203. Cham: Springer International Publishing, 2016. http://dx.doi.org/10.1007/164_2016_46.

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Labille, Jérôme, Natalia Pelinovskaya, Céline Botta, Jean-Yves Bottero, Armand Masion, Dilip S. Joag, Richard G. Forbes, et al. "Free Flow Aoustophoresis (FFA)." In Encyclopedia of Nanotechnology, 884. Dordrecht: Springer Netherlands, 2012. http://dx.doi.org/10.1007/978-90-481-9751-4_100261.

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Schwaiger, Lisa. "VII.2 FF2: Typologie alternativer Nachrichtenmedien." In Gegen die Öffentlichkeit, 130–80. Bielefeld, Germany: transcript Verlag, 2022. http://dx.doi.org/10.14361/9783839461211-026.

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Mohapatra, Pradyumna, Sunita Panda, and Siba Prasada Panigrahi. "Equalizer Modeling Using FFA Trained Neural Networks." In Advances in Intelligent Systems and Computing, 569–77. Singapore: Springer Singapore, 2017. http://dx.doi.org/10.1007/978-981-10-5687-1_51.

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Ghislain, Julien, and Vincent Poitout. "The Role and Future of FFA1 as a Therapeutic Target." In Free Fatty Acid Receptors, 159–80. Cham: Springer International Publishing, 2016. http://dx.doi.org/10.1007/164_2016_51.

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Ichimura, Atsuhiko. "Polymorphic Variation in FFA Receptors: Functions and Consequences." In Free Fatty Acid Receptors, 133–58. Cham: Springer International Publishing, 2016. http://dx.doi.org/10.1007/164_2016_57.

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Pyeon, Cheol Ho. "Introduction." In Accelerator-Driven System at Kyoto University Critical Assembly, 1–12. Singapore: Springer Singapore, 2021. http://dx.doi.org/10.1007/978-981-16-0344-0_1.

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AbstractAt the Kyoto University Critical Assembly (KUCA), the accelerator-driven system (ADS) is composed of a solid-moderated and solid-reflected core (A-core) and a pulsed-neutron generator (14 MeV neutrons) or the fixed-filed alternating gradient (FFAG) accelerator (100 MeV protons). At KUCA, two external neutron sources, including 14 MeV neutrons and 100 MeV protons, are separately injected into the A-core, and employed for carrying out the ADS experiments. With the combined use of the A-core and two external neutron sources, basic and feasibility studies of ADS have been engaged in the examination of neutronics of ADS, through the measurements of statics and kinetics parameters of reactor physics, including subcritical multiplication factor, subcriticality, prompt neutron decay constant, effective delayed neutron fraction, neutron spectrum, and reaction rates.
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Hansen, Steffen V. F., and Trond Ulven. "Pharmacological Tool Compounds for the Free Fatty Acid Receptor 4 (FFA4/GPR120)." In Free Fatty Acid Receptors, 33–56. Cham: Springer International Publishing, 2016. http://dx.doi.org/10.1007/164_2016_60.

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Mohapatra, Pradumna, and Siba Prasada Panigrahi. "FFA Trained Radial Basis Function Neural Networks in Channel Equalization." In Swarm, Evolutionary, and Memetic Computing, 847–55. Cham: Springer International Publishing, 2015. http://dx.doi.org/10.1007/978-3-319-20294-5_72.

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Conference papers on the topic "FFA2"

1

Mills, F. E. "Early FFAG development." In CYCLOCTRONS AND THEIR APPLICATIONS 2001: Sixteenth International Conference. AIP, 2001. http://dx.doi.org/10.1063/1.1435232.

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Pasternak, J., J. Fourrier, E. Froidefond, B. Autin, F. Meot, D. Neuveglise, and T. Planche. "Spiral FFAG for protontherapy." In 2007 IEEE Particle Accelerator Conference (PAC). IEEE, 2007. http://dx.doi.org/10.1109/pac.2007.4440770.

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Méot, F., Osamu Yasuda, Naba Mondal, and Chihiro Ohmori. "The RACCAM FFAG Project." In NEUTRINO FACTORIES, SUPERBEAMS AND BETABEAMS: 9th International Workshop on Neutrino Factories, Superbeams, and Betabeams. AIP, 2008. http://dx.doi.org/10.1063/1.2898985.

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Mori, Yoshiharu. "Developments of FFAG Accelerators." In HIGH INTENSITY AND HIGH BRIGHTNESS HADRON BEAMS: 33rd ICFA Advanced Beam Dynamics Workshop on High Intensity and High Brightness Hadron Beams. AIP, 2005. http://dx.doi.org/10.1063/1.1949554.

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Sato, Akira. "FFAG Construction for PRISM." In NEUTRINO FACTORIES AND SUPERBEAMS: 5th International Workshop on Neutrino Factories and Superbeams; NuFact 03. AIP, 2004. http://dx.doi.org/10.1063/1.1818459.

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Machida, S., A. Yamazaki, T. Yokoi, M. Yoshii, M. Yoshimoto, Y. Yuasa, M. Matoba, et al. "Status of 150MeV FFAG synchrotron." In Proceedings of the 2003 Particle Accelerator Conference. IEEE, 2003. http://dx.doi.org/10.1109/pac.2003.1289945.

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Trbojevic, Dejan. "FFAG lattice without opposite bends." In Studies on colliders and collider physics at the highest energies. AIP, 2000. http://dx.doi.org/10.1063/1.1361693.

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Bogacz, S. Alex, B. S. Acharya, Maury Goodman, and Naba K. Mondal. "Muon Acceleration-RLA and FFAG." In 12TH INTERNATIONAL WORKSHOP ON NEUTRINO FACTORIES, SUPERBEAMS, AND BETABEAMS: NuFact10. AIP, 2011. http://dx.doi.org/10.1063/1.3644312.

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Aiba, Masamitsu. "Beam Dynamics of FFAG Accelerator." In HIGH INTENSITY AND HIGH BRIGHTNESS HADRON BEAMS: 20th ICFA Advanced Beam Dynamics Workshop on High Intensity and High Brightness Hadron Beams ICFA-HB2002. AIP, 2002. http://dx.doi.org/10.1063/1.1522626.

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Johnstone, C., and S. Koscielniak. "New nonscaling FFAG for medical applications." In 2007 IEEE Particle Accelerator Conference (PAC). IEEE, 2007. http://dx.doi.org/10.1109/pac.2007.4440631.

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Reports on the topic "FFA2"

1

Brooks, S. FFAG Cell Candidate February 2017. Office of Scientific and Technical Information (OSTI), February 2017. http://dx.doi.org/10.2172/1412717.

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Berg, J. Scott. FFAG Designs for Muon Collider Acceleration. Office of Scientific and Technical Information (OSTI), January 2014. http://dx.doi.org/10.2172/1119569.

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Berg, J. Scott. The EMMA Non-Scaling FFAG Experiment. Office of Scientific and Technical Information (OSTI), August 2011. http://dx.doi.org/10.2172/1439844.

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Ruggiero A. G. AGS-less RIA with FFAG Accelerators. Office of Scientific and Technical Information (OSTI), May 2006. http://dx.doi.org/10.2172/1061829.

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Ruggiero A. FFAG Accelerator Proton Driver for Neutrino Factory. Office of Scientific and Technical Information (OSTI), October 2005. http://dx.doi.org/10.2172/1061810.

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Ruggiero A. G., J. Alessi, E. Beebe, A. Pikin, T. Roser, and D. Trbojevic. FFAG-based Accelerator for Radio-Isotopes Production. Office of Scientific and Technical Information (OSTI), July 2007. http://dx.doi.org/10.2172/1061870.

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BERG, J. S. Dynamics in a Spiral FFAG with Tilted Cavities. Office of Scientific and Technical Information (OSTI), December 2007. http://dx.doi.org/10.2172/923368.

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Ruggiero A. G., M. Blaskiewicz, E. Courant, D. Trbojevic, N. Tsoupas, and W. Zhang. 1.5-GeV FFAG Accelerator for the AGS Facility. Office of Scientific and Technical Information (OSTI), February 2004. http://dx.doi.org/10.2172/1061730.

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Berg, J. S. Beam Loading Computation for the IDS-NF FFAG. Office of Scientific and Technical Information (OSTI), October 2011. http://dx.doi.org/10.2172/1034063.

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Ruggiero A. CW Mode of Operation of a Proton FFAG Accelerator. Office of Scientific and Technical Information (OSTI), September 2005. http://dx.doi.org/10.2172/1061809.

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