Dysregulation of the mesolimbic dopamine system and reward in MCH-/- mice.

Background: The hypothalamic neuropeptide melanin-concentrating hormone (MCH) plays a critical role in energy homeostasis. Abundant expression of the MCH receptor is observed outside the hypothalamus, especially in the dorsal and the ventral striatum, raising the possibility that MCH modulates the function of the midbrain dopamine neurons and associated circuitry.

Methods: The MCH receptor 1 (MCHR1) expression was assessed by in situ hybridization.

MCH-/- mice are resistant to aging-associated increases in body weight and insulin resistance.

Ablation of the hypothalamic peptide, melanin-concentrating hormone (MCH), leads to a lean phenotype and resistance to diet-induced obesity. Observation of MCH(-/-) mice at older ages suggested that these effects persist in mice >1 year old. Leanness secondary to caloric restriction is known to be associated with improved glucose tolerance as well as an overall increase in life span.

Mice with MCH ablation resist diet-induced obesity through strain-specific mechanisms.

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).