Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Overview
  • Published:

Central (mainly) actions of GPCRs in energy homeostasis/balance: view from the Chair

International Journal of Obesity Supplements volume 4, pages S21–S25 (2014)Cite this article

Subjects

Abstract

To maintain a constant body weight, energy intake must equal energy expenditure; otherwise, there is a risk of overweight and obesity. The hypothalamus is one of the primary brain regions where multiple nutrient-related signals from peripheral and central sources converge and become integrated to regulate both short- and long-term nutritional states. The aim of the afternoon session of the 15th Annual International Symposium of the Laval University Obesity Research Chair held in Quebec City on 9 November 2012 was to present the most recent insights into the complex molecular mechanisms regulating food intake. The aims were to emphasize on the interaction between central and peripheral actions of some of the key players acting not only at the hypothalamic level but also at the periphery. Presentations were focused on melanocortin-3 receptor (MC3R) and melanin-concentrating hormone (MCH) as anorexigenic and orexigenic components of the hypothalamus, on endocannabinoid receptors, initially as a central neuromodulatory signal, and on glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) as peripheral signals. What becomes clear from these four presentations is that the regulation of food intake and energy homeostasis involves several overlapping pathways, and that we have only touched the tip of the iceberg. From the examples presented in this symposium, it could be expected that in the near future, in addition to a low-fat diet and exercise, a combination of appropriate peptides and small molecules is likely to become available to improve/facilitate the objectives of long-term maintenance of energy balance and body weight.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Cote M, Matias I, Lemieux I, Petrosino S, Almeras N, Despres JP et al. Circulating endocannabinoid levels, abdominal adiposity and related cardiometabolic risk factors in obese men. Int J Obes (Lond) 2007; 31: 692–699.

    Article  CAS  Google Scholar 

  2. Despres JP, Lemieux I . Abdominal obesity and metabolic syndrome. Nature 2006; 444: 881–887.

    Article  CAS  PubMed  Google Scholar 

  3. Lim S, Despres JP, Koh KK . Prevention of atherosclerosis in overweight/obese patients.In need of novel multi-targeted approaches. Circ J 2011; 75: 1019–1027.

    Article  CAS  PubMed  Google Scholar 

  4. Despres JP . Abdominal obesity and cardiovascular disease: is inflammation the missing link? Can J Cardiol 2012; 28: 642–652.

    Article  PubMed  Google Scholar 

  5. Schwartz MW, Gelling RW . Rats lighten up with MCH antagonist. Nat Med 2002; 8: 779–781.

    Article  CAS  PubMed  Google Scholar 

  6. Cone RD . Anatomy and regulation of the central melanocortin system. Nat Neurosci 2005; 8: 571–578.

    Article  CAS  PubMed  Google Scholar 

  7. Cone RD . Studies on the physiological functions of the melanocortin system. Endocr Rev 2006; 27: 736–749.

    Article  CAS  PubMed  Google Scholar 

  8. Garfield AS, Lam DD, Marston OJ, Przydzial MJ, Heisler LK . Role of central melanocortin pathways in energy homeostasis. Trends Endocrinol Metab 2009; 20: 203–215.

    Article  CAS  PubMed  Google Scholar 

  9. Klok MD, Jakobsdottir S, Drent ML . The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review. Obes Rev 2007; 8: 21–34.

    Article  CAS  PubMed  Google Scholar 

  10. Barsh GS, Schwartz MW . Genetic approaches to studying energy balance: perception and integration. Nat Rev Genet 2002; 3: 589–600.

    Article  CAS  PubMed  Google Scholar 

  11. Schwartz MW, Woods SC, Porte Jr D, Seeley RJ, Baskin DG . Central nervous system control of food intake. Nature 2000; 404: 661–671.

    Article  CAS  PubMed  Google Scholar 

  12. Farooqi IS, Drop S, Clements A, Keogh JM, Biernacka J, Lowenbein S et al. Heterozygosity for a POMC-null mutation and increased obesity risk in humans. Diabetes 2006; 55: 2549–2553.

    Article  CAS  PubMed  Google Scholar 

  13. Yaswen L, Diehl N, Brennan MB, Hochgeschwender U . Obesity in the mouse model of pro-opiomelanocortin deficiency responds to peripheral melanocortin. Nat Med 1999; 5: 1066–1070.

    Article  CAS  PubMed  Google Scholar 

  14. Butler AA . The melanocortin system and energy balance. Peptides 2006; 27: 281–290.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Begriche K, Sutton GM, Butler AA . Homeostastic and non-homeostatic functions of melanocortin-3 receptors in the control of energy balance and metabolism. Physiol Behav 2011; 104: 546–554.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Begriche K, Sutton GM, Fang J, Butler AA . The role of melanocortin neuronal pathways in circadian biology: a new homeostatic output involving melanocortin-3 receptors? Obes Rev 2009; 10 (Suppl 2): 14–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Butler AA, Kesterson RA, Khong K, Cullen MJ, Pelleymounter MA, Dekoning J et al. A unique metabolic syndrome causes obesity in the melanocortin-3 receptor-deficient mouse. Endocrinology 2000; 141: 3518–3521.

    Article  CAS  PubMed  Google Scholar 

  18. Sutton GM, Begriche K, Kumar KG, Gimble JM, Perez-Tilve D, Nogueiras R et al. Central nervous system melanocortin-3 receptors are required for synchronizing metabolism during entrainment to restricted feeding during the light cycle. FASEB J 2010; 24: 862–872.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Di Marzo V . The endocannabinoid system in obesity and type 2 diabetes. Diabetologia 2008; 51: 1356–1367.

    Article  CAS  PubMed  Google Scholar 

  20. Quarta C, Mazza R, Obici S, Pasquali R, Pagotto U . Energy balance regulation by endocannabinoids at central and peripheral levels. Trends Mol Med 2011; 17: 518–526.

    Article  CAS  PubMed  Google Scholar 

  21. Kunos G, Tam J . The case for peripheral CB(1) receptor blockade in the treatment of visceral obesity and its cardiometabolic complications. Br J Pharmacol 2011; 163: 1423–1431.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Di Marzo V . Endocannabinoids: an appetite for fat. Proc Natl Acad Sci USA 2011; 108: 12567–12568.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Pertwee RG . Emerging strategies for exploiting cannabinoid receptor agonists as medicines. Br J Pharmacol 2009; 156: 397–411.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Tschop M, Smiley DL, Heiman ML . Ghrelin induces adiposity in rodents. Nature 2000; 407: 908–913.

    Article  CAS  PubMed  Google Scholar 

  25. Schwartz MW, Morton GJ . Obesity: keeping hunger at bay. Nature 2002; 418: 595–597.

    Article  CAS  PubMed  Google Scholar 

  26. Castaneda TR, Tong J, Datta R, Culler M, Tschop MH . Ghrelin in the regulation of body weight and metabolism. Front Neuroendocrinol 2010; 31: 44–60.

    Article  CAS  PubMed  Google Scholar 

  27. Rodgers RJ, Tschop MH, Wilding JP . Anti-obesity drugs: past, present and future. Dis Model Mech 2012; 5: 621–626.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Soria-Gomez E, Marquez-Diosdado MI, Montes-Rodriguez CJ, Estrada-Gonzalez V, Prospero-Garcia O . Oleamide administered into the nucleus accumbens shell regulates feeding behaviour via CB1 and 5-HT2C receptors. Int J Neuropsychopharmacol 2010; 13: 1247–1254.

    Article  CAS  PubMed  Google Scholar 

  29. Di Marzo V, Goparaju SK, Wang L, Liu J, Batkai S, Jarai Z et al. Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature 2001; 410: 822–825.

    Article  CAS  PubMed  Google Scholar 

  30. Cardinal P, Bellocchio L, Clark S, Cannich A, Klugmann M, Lutz B et al. Hypothalamic CB1 cannabinoid receptors regulate energy balance in mice. Endocrinology 2012; 153: 4136–4143

    Article  CAS  PubMed  Google Scholar 

  31. Bisogno T, Mahadevan A, Coccurello R, Chang JW, Allara M, Chen Y et al. A novel fluorophosphonate inhibitor of the biosynthesis of the endocannabinoid 2-arachidonoylglycerol with potential anti-obesity effects. Br J Pharmacol 2013; 169: 784–793.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Higuchi S, Irie K, Yamaguchi R, Katsuki M, Araki M, Ohji M et al. Hypothalamic 2-arachidonoylglycerol regulates multistage process of high-fat diet preferences. PLoS One 2012; 7: e38609##

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Yi CX, Tschop MH, Woods SC, Hofmann SM . High-fat-diet exposure induces IgG accumulation in hypothalamic microglia. Dis Model Mech 2012; 5: 686–690.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Thaler JP, Yi CX, Schur EA, Guyenet SJ, Hwang BH, Dietrich MO et al. Obesity is associated with hypothalamic injury in rodents and humans. J Clin Invest 2012; 122: 153–162.

    Article  CAS  PubMed  Google Scholar 

  35. Horvath TL, Diano S . The floating blueprint of hypothalamic feeding circuits. Nat Rev Neurosci 2004; 5: 662–667.

    Article  CAS  PubMed  Google Scholar 

  36. Day JW, Ottaway N, Patterson JT, Gelfanov V, Smiley D, Gidda J et al. A new glucagon and GLP-1 co-agonist eliminates obesity in rodents. Nat Chem Biol 2009; 5: 749–757.

    Article  CAS  PubMed  Google Scholar 

  37. Finan B, Yang B, Ottaway N, Stemmer K, Muller TD, Yi CX et al. Targeted estrogen delivery reverses the metabolic syndrome. Nat Med 2012; 18: 1847–1856.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Nahon JL . The melanocortins and melanin-concentrating hormone in the central regulation of feeding behavior and energy homeostasis. C R Biol 2006; 329: 623–638; discussion 653-625##

    Article  CAS  PubMed  Google Scholar 

  39. Peek CB, Ramsey KM, Marcheva B, Bass J . Nutrient sensing and the circadian clock. Trends Endocrinol Metab 2012; 23: 312–318.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Saper CB, Scammell TE, Lu J . Hypothalamic regulation of sleep and circadian rhythms. Nature 2005; 437: 1257–1263.

    Article  CAS  PubMed  Google Scholar 

  41. Scheer FA, Hilton MF, Mantzoros CS, Shea SA . Adverse metabolic and cardiovascular consequences of circadian misalignment. Proc Natl Acad Sci USA 2009; 106: 4453–4458.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Butler AA, Kozak LP . A recurring problem with the analysis of energy expenditure in genetic models expressing lean and obese phenotypes. Diabetes 2010; 59: 323–329.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Sutton GM, Perez-Tilve D, Nogueiras R, Fang J, Kim JK, Cone RD et al. The melanocortin-3 receptor is required for entrainment to meal intake. J Neurosci 2008; 28: 12946–12955.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Begriche K, Levasseur PR, Zhang J, Rossi J, Skorupa D, Solt LA et al. Genetic dissection of the functions of the melanocortin-3 receptor, a seven-transmembrane G-protein-coupled receptor, suggests roles for central and peripheral receptors in energy homeostasis. J Biol Chem 2011; 286: 40771–40781.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Begriche K, Marston OJ, Rossi J, Burke LK, McDonald P, Heisler LK et al. Melanocortin-3 receptors are involved in adaptation to restricted feeding. Genes Brain Behav 2012; 11: 291–302.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Yi CX, Tschop MH . Brain-gut-adipose-tissue communication pathways at a glance. Dis Model Mech 2012; 5: 583–587.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Cagampang FR, Poore KR, Hanson MA . Developmental origins of the metabolic syndrome: body clocks and stress responses. Brain Behav Immun 2011; 25: 214–220.

    Article  CAS  PubMed  Google Scholar 

  48. Heyman E, Gamelin FX, Aucouturier J, Di Marzo V . The role of the endocannabinoid system in skeletal muscle and metabolic adaptations to exercise: potential implications for the treatment of obesity. Obes Rev 2012; 13: 1110–1124.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from the Canadian Institute of Health Research to Nicole Gallo-Payet (MOP27912). NGP is a past recipient of a Canada Research Chair in Endocrinology of the Adrenal Gland.

Author information

Authors and Affiliations

  1. Division of Endocrinology, Department of Medicine, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, Quebec, Canada,

    N Gallo-Payet

Authors
  1. N Gallo-Payet
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to N Gallo-Payet.

Ethics declarations

Competing interests

The author declares no conflict of interest.

Additional information

This article is published as part of a supplement sponsored by the Université Laval's Research Chair in Obesity in an effort to inform the public on the causes, consequences, treatments, and prevention of obesity.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gallo-Payet, N. Central (mainly) actions of GPCRs in energy homeostasis/balance: view from the Chair. Int J Obes Supp 4 (Suppl 1), S21–S25 (2014). https://doi.org/10.1038/ijosup.2014.7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ijosup.2014.7

Keywords

Search

Advanced search

Quick links