Melanin-concentrating hormone overexpression in transgenic mice leads to obesity and insulin resistance.
J Clin Invest
; 107(3): 379-86, 2001 Feb.
Article
in En
| MEDLINE
| ID: mdl-11160162
ABSTRACT
Several lines of investigation suggest that the hypothalamic neuropeptide melanin-concentrating hormone (MCH) regulates body weight in mammals. Obese mice lacking functional leptin overexpress the MCH message in the fed or fasted state. Acute intracerebroventricular injection of MCH increases energy intake in rats. Mice lacking the MCH gene are lean. To test the hypothesis that chronic overexpression of MCH in mice causes obesity, we produced transgenic mice that overexpress MCH (MCH-OE) in the lateral hypothalamus at approximately twofold higher levels than normal mice. On the FVB genetic background, homozygous transgenic animals fed a high-fat diet ate 10% more and were 12% heavier at 13 weeks of age than wild-type animals, and they had higher systemic leptin levels. Blood glucose levels were higher both preprandially and after an intraperitoneal glucose injection. MCH-OE animals were insulin-resistant, as demonstrated by markedly higher plasma insulin levels and a blunted response to insulin; MCH-OE animals had only a 5% decrease in blood glucose after insulin administration, compared with a 31% decrease in wild-type animals. MCH-OE animals also exhibited a twofold increase in islet size. To evaluate the contribution of genetic background to the predisposition to obesity seen in MCH-OE mice, the transgene was bred onto the C57BL/6J background. Heterozygote C57BL/6J mice expressing the transgene showed increased body weight on a standard diet, confirming that MCH overexpression can lead to obesity.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pituitary Hormones
/
Insulin Resistance
/
Hypothalamic Hormones
/
Hypothalamus
/
Melanins
/
Obesity
Limits:
Animals
Language:
En
Journal:
J Clin Invest
Year:
2001
Type:
Article
Affiliation country:
United States