The role of melanin-concentrating hormone in energy homeostasis and mood disorders.
The melanin-concentrating hormone (MCH) is a cyclic peptide exerting its actions through two G-protein-coupled receptors, MCHR1 and MCHR2. MCH is implicated in the regulation of different physiological functions, including energy homeostasis and mood that is supported by the distribution of MCH and MCHR1 in the hypothalamus as well as corticolimbic structures. Genetic manipulation of MCH and MCHR1 results in a lean phenotype with increased resting energy expenditure as well as anxiolytic and antidepressant phenotypes. Similar observations have been demonstrated pharmacologically using different classes of selective MCHR1 antagonists. Here, we summarize the reported genetic and pharmacological evidence for the role played by the MCH system in the regulation of both energy homeostasis and mood disorders. We also comment on the utility of small-molecule MCHR1 antagonists for the treatment of obesity and affective disorders compared to existing therapies and provide a critical overview of the potential risks.
Wyeth Research, CN 8000, Princeton, NJ 08540, USA. antali@wyeth.com
Ildiko
I
Antal-Zimanyi
Xavier
X
Khawaja
D000339:Affect / Q000502:physiology; D000818:Animals; D030801:Animals, Genetically Modified; D004435:Eating; D004734:Energy Metabolism / Q000502:physiology*; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D007028:Hypothalamic Hormones / Q000235:genetics / Q000378:metabolism*; D008543:Melanins / Q000235:genetics / Q000378:metabolism*; D019964:Mood Disorders / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D010907:Pituitary Hormones / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D011979:Receptors, Pituitary Hormone / Q000235:genetics / Q000378:metabolism*; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
D007028:Hypothalamic Hormones; C103263:MCHR1 protein, human; C431280:MCHR2 protein, human; D008543:Melanins; D010907:Pituitary Hormones; D043562:Receptors, G-Protein-Coupled; D011979:Receptors, Pituitary Hormone; D017481:Receptors, Somatostatin; C019463:melanin-concentrating hormone