Antiobesity Effect of a Melanin-Concentrating Hormone 1 Receptor Antagonist in Diet-Induced Obese Mice

Endocrinology. 2005 Jul;146(7):3080-6. doi: 10.1210/en.2004-1150. Epub 2005 Apr 7.

Abstract

Melanin-concentrating hormone (MCH) is a cyclic orexigenic peptide expressed in the lateral hypothalamus, which plays an important role in regulating energy balance. To elucidate the physiological role of MCH in obesity development, the present study examined the effect of a selective MCH1 receptor (MCH1R) antagonist in the diet-induced obesity mouse model. The MCH1R antagonist has high affinity and selectivity for MCH-1R and potently inhibits intracerebroventricularly injected MCH-induced food intake in Sprague Dawley rats. Chronic intracerebroventricular infusion of the MCH1R antagonist (7.5 microg/d) completely suppressed body weight gain in diet-induced obese mice during the treatment periods and significantly decreased cumulative food intake, by 14%. Carcass analysis showed that the MCH1R antagonist resulted in a selective decrease of body fat in the diet-induced obese mice. In addition, the MCH1R antagonist ameliorated the obesity-related hypercholesterolemia, hyperinsulinemia, hyperglycemia, and hyperleptinemia. These results indicate that MCH has a major role in the development of diet-induced obesity in mice and that a MCH1R antagonist might be a useful candidate as an antiobesity agent.

MeSH terms

  • Animals
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Diet*
  • Drug Administration Schedule
  • Eating / drug effects
  • Humans
  • Hypothalamic Hormones / administration & dosage
  • Hypothalamic Hormones / pharmacology
  • Injections, Intraventricular
  • Male
  • Melanins / administration & dosage
  • Melanins / pharmacology
  • Mice
  • Mice, Knockout
  • Motor Activity / drug effects
  • Obesity / etiology
  • Obesity / physiopathology*
  • Obesity / prevention & control*
  • Pituitary Hormones / administration & dosage
  • Pituitary Hormones / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Somatostatin / antagonists & inhibitors*
  • Receptors, Somatostatin / deficiency
  • Weight Gain / drug effects

Substances

  • Hypothalamic Hormones
  • MCHR1 protein, human
  • Melanins
  • Pituitary Hormones
  • Receptors, Somatostatin
  • melanin-concentrating hormone