Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and human

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, Koerner, 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 and Froguel, Philippe (2012) Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and human. Nature, 483 7389: 350-354. doi:10.1038/nature10798

Author 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
Koerner, 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
Title Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and human
Journal name Nature   Check publisher's open access policy
ISSN 0028-0836
Publication date 2012-03-01
Year available 2012
Sub-type Article (original research)
DOI 10.1038/nature10798
Open Access Status Not yet assessed
Volume 483
Issue 7389
Start page 350
End page 354
Total pages 5
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Formatted 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.
Keyword Multidisciplinary Sciences
Science & Technology - Other Topics
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID QLG1-CT-2000-01643
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
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