Title
Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and human Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and human
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Publication type
article
Publication
London ,
Subject
Engineering sciences. Technology
Source (journal)
Nature. - London
Volume/pages
483(2012) :7389 , p. 350-354
ISSN
0028-0836
ISI
000301481800053
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Free fatty acids provide an important energy source as nutrients, and act as signalling molecules in various cellular processes(1-4). Several G-protein-coupled receptors have been identified as free-fatty-acid receptors important in physiology as well as in several diseases(3,5-13). 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(5,6,14-16). 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.
E-info
https://repository.uantwerpen.be/docman/iruaauth/be76d7/3fd1469.pdf
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