Mice With MCH Ablation Resist Diet-Induced Obesity Through Strain-Specific Mechanisms

Am J Physiol Regul Integr Comp Physiol. 2005 Jul;289(1):R117-24. doi: 10.1152/ajpregu.00861.2004. Epub 2005 Feb 24.


Genetics and environment contribute to the development of obesity, in both humans and rodents. However, the potential interaction between genes important in energy balance, strain background, and dietary environment has been only minimally explored. We investigated the effects of genetic ablation of melanin-concentrating hormone (MCH), a neuropeptide with a key role in energy balance, with chow and a high-fat diet (HFD) in two different mouse strains, one obesity-prone (C57BL/6) and the other obesity-resistant (129). Substantial differences were seen in wild-type (WT) animals of different strains. 129 animals had significantly lower levels of spontaneous locomotor activity than C57BL/6; however, 129 mice gained less weight on both chow and HFD. In both strains, deletion of MCH led to attenuated weight gain compared with WT counterparts, an effect secondary to increased energy expenditure. In both strains, feeding a HFD led to further increases in energy expenditure in both WT and MCH-KO mice; however, this increase was more pronounced in 129 mice. In addition, mice lacking MCH have a phenotype of increased locomotor activity, an effect also seen in both strains. The relative increase in activity in MCH(-/-) mice is modest in animals fed chow but increases substantially when animals are placed on HFD. These studies reinforce the important role of MCH in energy homeostasis and indicate that MCH is a plausible target for antiobesity therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Body Composition
  • Body Weight
  • Diet*
  • Disease Susceptibility
  • Eating
  • Energy Metabolism
  • Genetic Predisposition to Disease
  • Glucose Tolerance Test
  • Hypothalamic Hormones / deficiency*
  • Insulin / blood
  • Leptin / blood
  • Melanins / deficiency*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Mice, Knockout
  • Motor Activity
  • Obesity / etiology*
  • Obesity / genetics
  • Oxygen Consumption
  • Pituitary Hormones / deficiency*
  • Species Specificity*
  • Thermogenesis


  • Hypothalamic Hormones
  • Insulin
  • Leptin
  • Melanins
  • Pituitary Hormones
  • melanin-concentrating hormone