Publication Date:
2012-02-22
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ichimura, Atsuhiko -- Hirasawa, Akira -- Poulain-Godefroy, Odile -- Bonnefond, Amelie -- Hara, Takafumi -- Yengo, Loic -- Kimura, Ikuo -- Leloire, Audrey -- Liu, Ning -- Iida, Keiko -- Choquet, Helene -- Besnard, Philippe -- Lecoeur, Cecile -- Vivequin, Sidonie -- Ayukawa, Kumiko -- Takeuchi, Masato -- Ozawa, Kentaro -- Tauber, Maithe -- Maffeis, Claudio -- Morandi, Anita -- Buzzetti, Raffaella -- Elliott, Paul -- Pouta, Anneli -- Jarvelin, Marjo-Riitta -- Korner, Antje -- Kiess, Wieland -- Pigeyre, Marie -- Caiazzo, Roberto -- Van Hul, Wim -- Van Gaal, Luc -- Horber, Fritz -- Balkau, Beverley -- Levy-Marchal, Claire -- Rouskas, Konstantinos -- Kouvatsi, Anastasia -- Hebebrand, Johannes -- Hinney, Anke -- Scherag, Andre -- Pattou, Francois -- Meyre, David -- Koshimizu, Taka-aki -- Wolowczuk, Isabelle -- Tsujimoto, Gozoh -- Froguel, Philippe -- G0500539/Medical Research Council/United Kingdom -- G0600705/Medical Research Council/United Kingdom -- England -- Nature. 2012 Feb 19;483(7389):350-4. doi: 10.1038/nature10798.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22343897" target="_blank"〉PubMed〈/a〉
Keywords:
Adipocytes/metabolism/pathology
;
Adipogenesis
;
Adipose Tissue/metabolism/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/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/genetics/*metabolism/pathology
;
Receptors, G-Protein-Coupled/deficiency/genetics/*metabolism
;
Signal Transduction/genetics
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink
