PMID:22343897

Citation	Ichimura, A, Hirasawa, A, Poulain-Godefroy, O, Bonnefond, A, Hara, T, Yengo, L, Kimura, I, Leloire, A, Liu, N, Iida, K, Choquet, H, Besnard, P, Lecoeur, C, Vivequin, S, Ayukawa, K, Takeuchi, M, Ozawa, K, Tauber, M, Maffeis, C, Morandi, A, Buzzetti, R, Elliott, P, Pouta, A, Jarvelin, MR, Körner, A, Kiess, W, Pigeyre, M, Caiazzo, R, Van Hul, W, Van Gaal, L, Horber, F, Balkau, B, Lévy-Marchal, C, Rouskas, K, Kouvatsi, A, Hebebrand, J, Hinney, A, Scherag, A, Pattou, F, Meyre, D, Koshimizu, TA, Wolowczuk, I, Tsujimoto, G and Froguel, P (2012) Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and human. Nature 483:350-4
Abstract	Free fatty acids provide an important energy source as nutrients, and act as signalling molecules in various cellular processes. Several G-protein-coupled receptors have been identified as free-fatty-acid receptors important in physiology as well as in several diseases. GPR120 (also known as O3FAR1) functions as a receptor for unsaturated long-chain free fatty acids and has a critical role in various physiological homeostasis mechanisms such as adipogenesis, regulation of appetite and food preference. Here we show that GPR120-deficient mice fed a high-fat diet develop obesity, glucose intolerance and fatty liver with decreased adipocyte differentiation and lipogenesis and enhanced hepatic lipogenesis. Insulin resistance in such mice is associated with reduced insulin signalling and enhanced inflammation in adipose tissue. In human, we show that GPR120 expression in adipose tissue is significantly higher in obese individuals than in lean controls. GPR120 exon sequencing in obese subjects reveals a deleterious non-synonymous mutation (p.R270H) that inhibits GPR120 signalling activity. Furthermore, the p.R270H variant increases the risk of obesity in European populations. Overall, this study demonstrates that the lipid sensor GPR120 has a key role in sensing dietary fat and, therefore, in the control of energy balance in both humans and rodents.
Links	PubMed Online version:10.1038/nature10798
Keywords	Adipocytes/metabolism; Adipocytes/pathology; Adipogenesis; Adipose Tissue/metabolism; Adipose Tissue/pathology; Animals; Calcium Signaling; Cell Differentiation; DNA Mutational Analysis; Diet, High-Fat; Energy Metabolism; Europe/ethnology; European Continental Ancestry Group/genetics; Exons/genetics; Fatty Liver/complications; Fatty Liver/genetics; Gene Expression Regulation; Glucagon-Like Peptide 1/secretion; Glucose/metabolism; Glucose Intolerance/complications; Humans; Insulin/metabolism; Insulin Resistance; Lipogenesis; Liver/metabolism; Macrophages/metabolism; Mice; Mutation/genetics; Obesity/complications; Obesity/genetics; Obesity/metabolism; Obesity/pathology; Receptors, G-Protein-Coupled/deficiency; Receptors, G-Protein-Coupled/genetics; Receptors, G-Protein-Coupled/metabolism; Signal Transduction/genetics
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:FFAR4		GO:0045444: fat cell differentiation	ECO:0000315:		P		Figure 2 suggests that in GPR120 deficient mice there was increased adipogenesis (fat cell differentiation) resulting in obesity.	complete CACAO 6238
MOUSE:FFAR4	involved_in	GO:0045444: fat cell differentiation	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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