scholarly journals Mining microarray datasets in nutrition: expression of the GPR120 (n-3 fatty acid receptor/sensor) gene is down-regulated in human adipocytes by macrophage secretions

2012 ◽  
Vol 1 ◽  
Author(s):  
Paul Trayhurn ◽  
Gareth Denyer
Keyword(s):  
Fatty Acid ◽  
Conditioned Medium ◽  
Mrna Level ◽  
Bioinformatic Analysis ◽  
Human Adipocytes ◽  
Acid Receptor ◽  
Microarray Datasets ◽  
G Protein Coupled ◽  
Source Of Information ◽  
Fatty Acid Receptor

AbstractMicroarray datasets are a rich source of information in nutritional investigation. Targeted mining of microarray data following initial, non-biased bioinformatic analysis can provide key insight into specific genes and metabolic processes of interest. Microarrays from human adipocytes were examined to explore the effects of macrophage secretions on the expression of the G-protein-coupled receptor (GPR) genes that encode fatty acid receptors/sensors. Exposure of the adipocytes to macrophage-conditioned medium for 4 or 24 h had no effect on GPR40 and GPR43 expression, but there was a marked stimulation of GPR84 expression (receptor for medium-chain fatty acids), the mRNA level increasing 13·5-fold at 24 h relative to unconditioned medium. Importantly, expression of GPR120, which encodes an n-3 PUFA receptor/sensor, was strongly inhibited by the conditioned medium (15-fold decrease in mRNA at 24 h). Macrophage secretions have major effects on the expression of fatty acid receptor/sensor genes in human adipocytes, which may lead to an augmentation of the inflammatory response in adipose tissue in obesity.

scholarly journals The Free Fatty Acid Receptor G Protein-coupled Receptor 40 (GPR40) Protects from Bone Loss through Inhibition of Osteoclast Differentiation

2013 ◽  
Vol 288 (9) ◽  
pp. 6542-6551 ◽  
Author(s):  
Fabien Wauquier ◽  
Claire Philippe ◽  
Laurent Léotoing ◽  
Sylvie Mercier ◽  
Marie-Jeanne Davicco ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Bone Loss ◽  
G Protein ◽  
Osteoclast Differentiation ◽  
G Protein Coupled Receptor ◽  
Acid Receptor ◽  
Free Fatty Acid Receptor ◽  
G Protein Coupled ◽  
Fatty Acid Receptor

Palmitate-induced increase in long-chain fatty acid receptor GPR120 mRNA level in LβT2 pituitary gonadotrope cells

2007 ◽  
Vol 58 ◽  
pp. S223
Author(s):  
Ryutaro Moriyama ◽  
Kazuhiro Nose ◽  
Azusa Kohama ◽  
Nobuyuki Fukushima
Keyword(s):  
Fatty Acid ◽  
Mrna Level ◽  
Chain Fatty Acid ◽  
Long Chain Fatty Acid ◽  
Acid Receptor ◽  
Long Chain ◽  
Fatty Acid Receptor

scholarly journals Homology modeling of FFA2 identifies novel agonists that potentiate insulin secretion

2017 ◽  
Vol 65 (8) ◽  
pp. 1116-1124 ◽  
Author(s):  
Stephanie R Villa ◽  
Rama K Mishra ◽  
Joseph L Zapater ◽  
Medha Priyadarshini ◽  
Annette Gilchrist ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Fatty Acid ◽  
Beta Cell ◽  
G Protein ◽  
Glucose Homeostasis ◽  
Beta Cell Proliferation ◽  
Acid Receptor ◽  
Biased Agonism ◽  
G Protein Coupled ◽  
Fatty Acid Receptor

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.

scholarly journals Distinct Phosphorylation Clusters Determine the Signaling Outcome of Free Fatty Acid Receptor 4/G Protein–Coupled Receptor 120

2016 ◽  
Vol 89 (5) ◽  
pp. 505-520 ◽  
Author(s):  
Rudi Prihandoko ◽  
Elisa Alvarez-Curto ◽  
Brian D. Hudson ◽  
Adrian J. Butcher ◽  
Trond Ulven ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
G Protein ◽  
G Protein Coupled Receptor ◽  
Acid Receptor ◽  
Free Fatty Acid Receptor ◽  
G Protein Coupled ◽  
Fatty Acid Receptor

FFAR4: A New Player in Cardiometabolic Disease?

Endocrinology ◽  
2021 ◽  
Author(s):  
Gage M Stuttgen ◽  
Daisy Sahoo
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
G Protein ◽  
Metabolic Diseases ◽  
The Body ◽  
Acid Receptor ◽  
Obesity And Diabetes ◽  
G Protein Coupled ◽  
Fatty Acid Receptor

Abstract Free fatty acids (FFAs) are implicated in the pathogenesis of metabolic diseases that include obesity, type 2 diabetes mellitus (T2DM), and cardiovascular disease (CVD). FFAs serve as ligands for free fatty acid receptors (FFARs) that belong to the family of rhodopsin-like G protein-coupled receptors (GPCRs) and are expressed throughout the body to maintain energy homeostasis under changing nutritional conditions. Free fatty acid receptor 4 (FFAR4), also known as G protein-coupled receptor 120 (GPR120), is a long-chain fatty acid receptor highly expressed in adipocytes, endothelial cells, and macrophages. Activation of FFAR4 helps maintain metabolic homeostasis by regulating adipogenesis, insulin sensitivity, and inflammation. Furthermore, dysfunction of FFAR4 is associated with insulin resistance, obesity, and eccentric remodeling in both humans and mice, making FFAR4 an attractive therapeutic target for treating or preventing metabolic diseases. While much of the previous literature on FFAR4 has focused on its role in obesity and diabetes, recent studies have demonstrated that FFAR4 may also play an important role in the development of atherosclerosis and CVD. Most notably, FFAR4 activation reduces monocyte-endothelial cell interaction, enhances cholesterol efflux from macrophages, reduces lesion size in atherogenic mouse models, and stimulates oxylipin production in myocytes that functions in a feed-forward cardioprotective mechanism. This review will focus on the role of FFAR4 in metabolic diseases and highlights an underappreciated role of FFAR4 in the development of atherosclerosis and CVD.

scholarly journals The G-Protein-Coupled Long-Chain Fatty Acid Receptor GPR40 and Glucose Metabolism

2014 ◽  
Vol 5 ◽  
Author(s):  
Tsutomu Tomita ◽  
Kiminori Hosoda ◽  
Junji Fujikura ◽  
Nobuya Inagaki ◽  
Kazuwa Nakao
Keyword(s):  
Fatty Acid ◽  
Glucose Metabolism ◽  
G Protein ◽  
Chain Fatty Acid ◽  
Long Chain Fatty Acid ◽  
Acid Receptor ◽  
G Protein Coupled ◽  
Long Chain ◽  
Fatty Acid Receptor
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