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

Nature volume 483, pages 350–354 (2012)Cite this article

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Abstract

Free fatty acids provide an important energy source as nutrients, and act as signalling molecules in various cellular processes1,2,3,4. Several G-protein-coupled receptors have been identified as free-fatty-acid receptors important in physiology as well as in several diseases3,5,6,7,8,9,10,11,12,13. 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 preference5,6,14,15,16. 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.

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Figure 1: Obesity, hypertrophic adipocytes, accumulation of pro-inflammatory macrophages and hepatic steatosis in HFD-fed GPR120-deficient mice.
Figure 2: Impaired glucose metabolism, adipogenesis and lipogenesis in HFD-fed GPR120-deficient mice.
Figure 3: GPR120 expression in human obese tissue samples, and effect of GPR120 variants on [Ca2+]i response and GLP-1 secretion.

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Primary accessions

Gene Expression Omnibus

Data deposits

Microarray data have been deposited in theNCBI Gene Expression Omnibus under accession number GSE32095.

Change history

  • 28 February 2012

    The Supplementary Tables were missing from the original supplementary information file and have since been added.

References

  1. Nunez, E. A. Biological complexity is under the ‘strange attraction’ of non-esterified fatty acids. Prostaglandins Leukot. Essent. Fatty Acids 57, 107–110 (1997)

    Article  CAS  PubMed  Google Scholar 

  2. Haber, E. P. et al. Pleiotropic effects of fatty acids on pancreatic β-cells. J. Cell. Physiol. 194, 1–12 (2003)

    Article  CAS  PubMed  Google Scholar 

  3. Itoh, Y. et al. Free fatty acids regulate insulin secretion from pancreatic beta cells through GPR40. Nature 422, 173–176 (2003)

    Article  ADS  CAS  PubMed  Google Scholar 

  4. Cao, H. et al. Identification of a lipokine, a lipid hormone linking adipose tissue to systemic metabolism. Cell 134, 933–944 (2008)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Hirasawa, A. et al. Free fatty acids regulate gut incretin glucagon-like peptide-1 secretion through GPR120. Nature Med. 11, 90–94 (2005)

    Article  CAS  PubMed  Google Scholar 

  6. Steneberg, P., Rubins, N., Bartoov-Shifman, R., Walker, M. D. & Edlund, H. The FFA receptor GPR40 links hyperinsulinemia, hepatic steatosis, and impaired glucose homeostasis in mouse. Cell Metab. 1, 245–258 (2005)

    Article  CAS  PubMed  Google Scholar 

  7. Wang, J., Wu, X., Simonavicius, N., Tian, H. & Ling, L. Medium-chain fatty acids as ligands for orphan G protein-coupled receptor GPR84. J. Biol. Chem. 281, 34457–34464 (2006)

    Article  CAS  PubMed  Google Scholar 

  8. Ichimura, A., Hirasawa, A., Hara, T. & Tsujimoto, G. Free fatty acid receptors act as nutrient sensors to regulate energy homeostasis. Prostaglandins Other Lipid Mediat. 89, 82–88 (2009)

    Article  CAS  PubMed  Google Scholar 

  9. Maslowski, K. M. et al. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature 461, 1282–1286 (2009)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  10. Ahmed, K. et al. An autocrine lactate loop mediates insulin-dependent inhibition of lipolysis through GPR81. Cell Metab. 11, 311–319 (2010)

    Article  CAS  PubMed  Google Scholar 

  11. Oh. Da, Y. et al. GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell 142, 687–698 (2010)

  12. Hara, T., Hirasawa, A., Ichimura, A., Kimura, I. & Tsujimoto, G. Free fatty acid receptors FFAR1 and GPR120 as novel therapeutic targets for metabolic disorders. J. Pharm. Sci. 100, 3594–3601 (2011)

    Article  CAS  PubMed  Google Scholar 

  13. Kimura, I. et al. Short-chain fatty acids and ketones directly regulate sympathetic nervous system via G protein-coupled receptor 41 (GPR41). Proc. Natl Acad. Sci. USA 108, 8030–8035 (2011)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  14. Gotoh, C. et al. The regulation of adipogenesis through GPR120. Biochem. Biophys. Res. Commun. 354, 591–597 (2007)

    Article  CAS  PubMed  Google Scholar 

  15. Tanaka, T. et al. Free fatty acids induce cholecystokinin secretion through GPR120. Naunyn Schmiedebergs Arch. Pharmacol. 377, 523–527 (2008)

    Article  CAS  PubMed  Google Scholar 

  16. Miyauchi, S. et al. Distribution and regulation of protein expression of the free fatty acid receptor GPR120. Naunyn Schmiedebergs Arch. Pharmacol. 379, 427–434 (2009)

    Article  CAS  PubMed  Google Scholar 

  17. Kido, Y. et al. Tissue-specific insulin resistance in mice with mutations in the insulin receptor, IRS-1, and IRS-2. J. Clin. Invest. 105, 199–205 (2000)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Bernal-Mizrachi, E., Wen, W., Stahlhut, S., Welling, C. M. & Permutt, M. A. Islet beta cell expression of constitutively active Akt1/PKB alpha induces striking hypertrophy, hyperplasia, and hyperinsulinemia. J. Clin. Invest. 108, 1631–1638 (2001)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Hosooka, T. et al. Dok1 mediates high-fat diet-induced adipocyte hypertrophy and obesity through modulation of PPAR-γ phosphorylation. Nature Med. 14, 188–193 (2008)

    Article  CAS  PubMed  Google Scholar 

  20. Ntambi, J. M. et al. Loss of stearoyl-CoA desaturase-1 function protects mice against adiposity. Proc. Natl Acad. Sci. USA 99, 11482–11486 (2002)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  21. Gutierrez-Juarez, R. et al. Critical role of stearoyl-CoA desaturase-1 (SCD1) in the onset of diet-induced hepatic insulin resistance. J. Clin. Invest. 116, 1686–1695 (2006)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Jeyakumar, S. M. et al. Fatty acid desaturation index correlates with body mass and adiposity indices of obesity in Wistar NIN obese mutant rat strains WNIN/Ob and WNIN/GR-Ob. Nutr. Metab. (Lond.) 6, 27 (2009)

    Article  Google Scholar 

  23. Brown, J. M. et al. Combined therapy of dietary fish oil and stearoyl-CoA desaturase 1 inhibition prevents the metabolic syndrome and atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 30, 24–30 (2010)

    Article  CAS  PubMed  Google Scholar 

  24. Ichimura, A., Ruike, Y., Terasawa, K., Shimizu, K. & Tsujimoto, G. MicroRNA-34a inhibits cell proliferation by repressing mitogen-activated protein kinase kinase 1 during megakaryocytic differentiation of K562 cells. Mol. Pharmacol. 77, 1016–1024 (2010)

    Article  CAS  PubMed  Google Scholar 

  25. Hara, T. et al. Novel selective ligands for free fatty acid receptors GPR120 and GPR40. Naunyn Schmiedebergs Arch. Pharmacol. 380, 247–255 (2009)

    Article  CAS  PubMed  Google Scholar 

  26. Sun, Q. et al. Structure-activity relationships of GPR120 agonists based on a docking simulation. Mol. Pharmacol. 78, 804–810 (2010)

    Article  CAS  PubMed  Google Scholar 

  27. Gautier, L., Cope, L., Bolstad, B. M. & Irizarry, R. A. affy–analysis of Affymetrix GeneChip data at the probe level. Bioinformatics 20, 307–315 (2004)

    Article  CAS  PubMed  Google Scholar 

  28. Poulain-Godefroy, O., Lecoeur, C., Pattou, F., Fruhbeck, G. & Froguel, P. Inflammation is associated with a decrease of lipogenic factors in omental fat in women. Am. J. Physiol. Regul. Integr. Comp. Physiol. 295, R1–R7 (2008)

    Article  CAS  PubMed  Google Scholar 

  29. Meyre, D. et al. Genome-wide association study for early-onset and morbid adult obesity identifies three new risk loci in European populations. Nature Genet. 41, 157–159 (2009)

    Article  CAS  PubMed  Google Scholar 

  30. Morandi, A. et al. The Q121 variant of ENPP1 may protect from childhood overweight/obesity in the Italian population. Obesity (Silver Spring) 17, 202–206 (2009)

    Article  CAS  Google Scholar 

  31. Buzzetti, R. et al. PPAR-γ2 Pro12Ala variant is associated with greater insulin sensitivity in childhood obesity. Pediatr. Res. 57, 138–140 (2005)

    Article  CAS  PubMed  Google Scholar 

  32. Järvelin, M. R. et al. Ecological and individual predictors of birthweight in a northern Finland birth cohort 1986. Paediatr. Perinat. Epidemiol. 11, 298–312 (1997)

    Article  PubMed  Google Scholar 

  33. Peeters, A. et al. Variants in the FTO gene are associated with common obesity in the Belgian population. Mol. Genet. Metab. 93, 481–484 (2008)

    Article  CAS  PubMed  Google Scholar 

  34. Steffen, R., Potoczna, N., Bieri, N. & Horber, F. F. Successful multi-intervention treatment of severe obesity: a 7-year prospective study with 96% follow-up. Obes. Surg. 19, 3–12 (2009)

    Article  PubMed  Google Scholar 

  35. Rouskas, K. et al. Association between BBS6/MKKS gene polymorphisms, obesity and metabolic syndrome in the Greek population. Int. J. Obes. (Lond.) 32, 1618–1625 (2008)

    Article  ADS  CAS  Google Scholar 

  36. Balkau, B. An epidemiologic survey from a network of French Health Examination Centres (D.E.S.I.R.): epidemiologic data on the insulin resistance syndrome [in French]. Rev. Epidemiol. Sante Publique 44, 373–375 (1996)

    CAS  PubMed  Google Scholar 

  37. Jaquet, D., Collin, D., Levy-Marchal, C. & Czernichow, P. Adult height distribution in subjects born small for gestational age. Horm. Res. 62, 92–96 (2004)

    CAS  PubMed  Google Scholar 

  38. Meyre, D. et al. R125W coding variant in TBC1D1 confers risk for familial obesity and contributes to linkage on chromosome 4p14 in the French population. Hum. Mol. Genet. 17, 1798–1802 (2008)

    Article  CAS  PubMed  Google Scholar 

  39. Jarick, I. et al. Novel common copy number variation for early onset extreme obesity on chromosome 11q11 identified by a genome-wide analysis. Hum. Mol. Genet. 20, 840–852 (2011)

    Article  CAS  PubMed  Google Scholar 

  40. Poskitt, E. M. Defining childhood obesity: the relative body mass index (BMI). European Childhood Obesity group. Acta Paediatr. 84, 961–963 (1995)

    Article  CAS  PubMed  Google Scholar 

  41. Rolland-Cachera, M. F. et al. Body mass index variations: centiles from birth to 87 years. Eur. J. Clin. Nutr. 45, 13–21 (1991)

    CAS  PubMed  Google Scholar 

  42. Siepel, A. et al. Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. Genome Res. 15, 1034–1050 (2005)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Ramensky, V., Bork, P. & Sunyaev, S. Human non-synonymous SNPs: server and survey. Nucleic Acids Res. 30, 3894–3900 (2002)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Sunyaev, S. et al. Prediction of deleterious human alleles. Hum. Mol. Genet. 10, 591–597 (2001)

    Article  CAS  PubMed  Google Scholar 

  45. Thomas, P. D. et al. PANTHER: a library of protein families and subfamilies indexed by function. Genome Res. 13, 2129–2141 (2003)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Kumar, P., Henikoff, S. & Ng, P. C. Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nature Protocols 4, 1073–1081 (2009)

    Article  CAS  PubMed  Google Scholar 

  47. Bromberg, Y., Yachdav, G. & Rost, B. SNAP predicts effect of mutations on protein function. Bioinformatics 24, 2397–2398 (2008)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Ferrer-Costa, C. et al. PMUT: a web-based tool for the annotation of pathological mutations on proteins. Bioinformatics 21, 3176–3178 (2005)

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We are indebted to all subjects who participated in these studies. In Japan, the study was supported in part by research grants from the Japan Society for the Promotion of Science; the Ministry of Education, Culture, Sports, Science and Technology of Japan; the Japan Science and Technology Agency; and the Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program), initiated by the Council for Science and Technology Policy. A.I. is a fellow of the Japan Society for the Promotion of Science. A.B. is a fellow of the EU-funded EUROCHIP consortium. In France, the study was supported by le Conseil Régional Nord Pas de Calais/FEDER and the Agence Nationale de la Recherche (Programme de Recherche en Nutrition et Alimentation, SensoFAT). The Northern Finland Birth Cohort Studies 1986 received financial support from the Academy of Finland, the University Hospital of Oulu (Finland), the University of Oulu (Finland), the European Commission (EURO-BLCS, Framework 5 award QLG1-CT-2000-01643), and the Medical Research Council (G0500539, G0600705, PrevMetSyn/SALVE). We thank the ABOS consortium and the CIC-CCPPRB (Lille CHRU) team for their help in sample handling and clinical data collection. We are grateful to M. Deweirder and F. Allegaert for human DNA bank management.

Author information

Author notes

  1. Atsuhiko Ichimura, Akira Hirasawa, Odile Poulain-Godefroy and Amélie Bonnefond: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan,

    Atsuhiko Ichimura, Akira Hirasawa, Takafumi Hara, Ikuo Kimura, Ning Liu, Keiko Iida, Kumiko Ayukawa, Masato Takeuchi, Kentaro Ozawa & Gozoh Tsujimoto

  2. Centre National de la Recherche Scientifique (CNRS)-Unité mixte de recherche (UMR) 8199, Lille Pasteur Institute, Lille 59000, France,

    Odile Poulain-Godefroy, Amélie Bonnefond, Loïc Yengo, Audrey Leloire, Hélène Choquet, Cécile Lecoeur, Sidonie Vivequin, Anita Morandi, Konstantinos Rouskas, David Meyre, Isabelle Wolowczuk & Philippe Froguel

  3. Lille Nord de France University, Lille 59000, France,

    Odile Poulain-Godefroy, Amélie Bonnefond, Loïc Yengo, Audrey Leloire, Hélène Choquet, Cécile Lecoeur, Sidonie Vivequin, Anita Morandi, Konstantinos Rouskas, David Meyre, Isabelle Wolowczuk & Philippe Froguel

  4. Institut National de la Santé et de la Recherche Médicale (Inserm)-UMR U866, Physiologie de la Nutrition, Bourgogne University, AgroSup Dijon, Dijon 21078, France,

    Philippe Besnard

  5. Inserm-U563, Children’s Hospital, Centre Hospitalier Universitaire, Toulouse 31000, France,

    Maithé Tauber

  6. Regional Centre for Juvenile Diabetes, Obesity and Clinical Nutrition, Verona 37134, Italy,

    Claudio Maffeis & Anita Morandi

  7. Department of Mother and Child, Biology-Genetics, Section of Paediatrics, University of Verona, Verona 37134, Italy,

    Claudio Maffeis

  8. Department of Clinical Sciences, La Sapienza University, Rome 00161, Italy,

    Raffaella Buzzetti

  9. Department of Epidemiology and Biostatistics, Medical Research Council-HPA Centre for Environment and Health, School of Public Health, St Mary’s campus, Imperial College London, London W2 1PG, UK,

    Paul Elliott & Marjo-Riitta Jarvelin

  10. National Public Health Institute, Biocenter Oulu, University of Oulu, Oulu 90220, Finland,

    Anneli Pouta & Marjo-Riitta Jarvelin

  11. Institute of Clinical Medicine/Obstetrics and Gynecology, University of Oulu, Oulu 90220, Finland,

    Anneli Pouta

  12. Institute of Health Sciences, University of Oulu, Oulu 90220, Finland,

    Marjo-Riitta Jarvelin

  13. Department of Women’s & Child Health, Center for Pediatric Research, University of Leipzig, Leipzig 04317, Germany,

    Antje Körner & Wieland Kiess

  14. Inserm-U859, Lille Nord de France University, Lille 59000, France,

    Marie Pigeyre, Roberto Caiazzo & François Pattou

  15. Lille University Hospital, Nutrition, Lille 59000, France,

    Marie Pigeyre

  16. Lille University Hospital, Endocrine Surgery, Lille 59000, France,

    Roberto Caiazzo & François Pattou

  17. Department of Medical Genetics, University of Antwerp, Antwerp 2610, Belgium,

    Wim Van Hul

  18. Department of Endocrinology, Antwerp University Hospital, Antwerp 2650, Belgium,

    Luc Van Gaal

  19. Department of Surgery and Internal Medicine, Medical Department, Clinic Lindberg, Winterthur 8400, and University of Berne, Berne 3011, Switzerland,

    Fritz Horber

  20. Inserm-U780, Centre for research in Epidemiology and Population Health (CRESP), Villejuif 94800, France,

    Beverley Balkau

  21. Paris-Sud 11 University, Orsay 91405, France,

    Beverley Balkau

  22. Inserm-U690, Robert Debré hospital, Paris 75935, France,

    Claire Lévy-Marchal

  23. Department of Genetics, Development and Molecular Biology, School of Biology, Aristotle University of Thessaloniki, Thessaloniki 541 24, Greece,

    Konstantinos Rouskas & Anastasia Kouvatsi

  24. Department of Child and Adolescent Psychiatry, University of Duisburg-Essen, Essen 45147, Germany,

    Johannes Hebebrand & Anke Hinney

  25. Institute for Medical Informatics, Biometry and Epidemiology, University of Duisburg-Essen, Essen 45122, Germany,

    Andre Scherag

  26. McMaster University, Hamilton, Ontario L8S 4L8, Canada,

    David Meyre

  27. Department of Pharmacology, Division of Molecular Pharmacology, Jichi Medical University, Tochigi 329-0498, Japan,

    Taka-aki Koshimizu

  28. Department of Genomics of Common Disease, School of Public Health, Imperial College London, Hammersmith Hospital, London W12 0NN, UK,

    Philippe Froguel

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  1. Atsuhiko Ichimura
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Contributions

A.I., A. Hirasawa, O.P.-G. and A.B. are equally contributing first authors. G.T. and P.F. had the ideas for the mouse and human projects, respectively. A.I., A. Hirasawa, A.B., P.F. and G.T. drafted the manuscript. O.P.-G., H.C., D.M. and I.W. edited the manuscript and contributed to discussions. A. Hirasawa and G.T. designed the mouse research. A.I., A. Hirasawa, K.I. and G.T. created Gpr120-mutant mice. A.I., A. Hirasawa, A. Körner, T.H., I.K., T.-a.K., K.A., M. Takeuchi, K.O., N.L. and G.T. conducted biochemical and histochemical analyses for the mouse study. A.I. and A. Hirasawa performed bioinformatic analysis for the mouse study. L.Y. and C.L. performed the statistical analyses, and A.B. contributed to statistical analyses for the human study. O.P.-G. and I.W. designed the human expression gene study. A.L. performed the human expression gene study. H.C. and S.V. performed GPR120 sequencing and variant genotyping, respectively. P.B., M. Tauber, C.M., A.M., R.B., P.E., M.-R.J., W.V.H., L.V.G., F.H., B.B., C.L.-M., K.R., A. Kouvatsi and F.P. contributed to cohort-study samples and researched data.

Corresponding authors

Correspondence to Gozoh Tsujimoto or Philippe Froguel.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains Supplementary Figures 1-7 with legends and Supplementary Tables 1-7. The Supplementary Tables were missing from the original file posted on line and were added on 28 February 2012. (PDF 2380 kb)

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Ichimura, A., Hirasawa, A., Poulain-Godefroy, O. et al. Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and human. Nature 483, 350–354 (2012). https://doi.org/10.1038/nature10798

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