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Title: Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and human.
Authors: Ichimura, Atsuhiko  kyouindb  KAKEN_id  orcid (unconfirmed)
Hirasawa, Akira  kyouindb  KAKEN_id  orcid (unconfirmed)
Poulain-Godefroy, Odile
Bonnefond, Amélie
Hara, Takafumi
Yengo, Loïc
Kimura, Ikuo  kyouindb  KAKEN_id
Leloire, Audrey
Liu, Ning
Iida, Keiko
Choquet, Hélène
Besnard, Philippe
Lecoeur, Cécile
Vivequin, Sidonie
Ayukawa, Kumiko
Takeuchi, Masato
Ozawa, Kentaro
Tauber, Maithé
Maffeis, Claudio
Morandi, Anita
Buzzetti, Raffaella
Elliott, Paul
Pouta, Anneli
Jarvelin, Marjo-Riitta
Körner, Antje
Kiess, Wieland
Pigeyre, Marie
Caiazzo, Roberto
Van Hul, Wim
Van Gaal, Luc
Horber, Fritz
Balkau, Beverley
Lévy-Marchal, Claire
Rouskas, Konstantinos
Kouvatsi, Anastasia
Hebebrand, Johannes
Hinney, Anke
Scherag, Andre
Pattou, François
Meyre, David
Koshimizu, Taka-Aki
Wolowczuk, Isabelle
Tsujimoto, Gozoh
Froguel, Philippe
Author's alias: 辻本, 豪三
平澤, 明
市村, 敦彦
Issue Date: 19-Feb-2012
Publisher: Nature Publishing Group
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, Froguel P. Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and human. Nature. 2012 Feb 19. doi: 10.1038/nature10798.
Journal title: Nature
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.
Description: 脂肪センサーGPR120が食事性肥満の原因遺伝子であることの発見. 京都大学プレスリリース. 2012-02-20.
Rights: ©2012 Macmillan Publishers Limited. All rights reserved
This is not the published version. Please cite only the published version.
DOI(Published Version): 10.1038/nature10798
PubMed ID: 22343897
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