| First Author | Segal-Lieberman G | Year | 2003 |
| Journal | Proc Natl Acad Sci U S A | Volume | 100 |
| Issue | 17 | Pages | 10085-90 |
| PubMed ID | 12897241 | Mgi Jnum | J:85176 |
| Mgi Id | MGI:2673040 | Doi | 10.1073/pnas.1633636100 |
| Citation | Segal-Lieberman G, et al. (2003) Melanin-concentrating hormone is a critical mediator of the leptin-deficient phenotype. Proc Natl Acad Sci U S A 100(17):10085-90 |
| abstractText | Energy homeostasis is regulated by a complex network involving peripheral and central signals that determine food intake and energy expenditure. Melanin-concentrating hormone (MCH) plays an essential role in this process. Animals treated with MCH develop hyperphagia and obesity. Ablation of the prepro-MCH gene leads to a lean phenotype, as does ablation of the rodent MCH receptor, MCHR-1. MCH is overexpressed in the leptin-deficient ob/ob mouse, and we hypothesized that ablation of MCH in this animal would lead to attenuation of its obese phenotype. Compared with ob/ob animals, mice lacking both leptin and MCH (double null) had a dramatic reduction in body fat. Surprisingly, the hyperphagia of the ob/ob mouse was unaffected. Instead, leanness was secondary to a marked increase in energy expenditure resulting from both increased resting energy expenditure and locomotor activity. Furthermore, double-null mice showed improvements in other parameters impaired in ob/ob mice. Compared with ob/ob mice, double-null animals had increased basal body temperature, improved response to cold exposure, lower plasma glucocorticoid levels, improved glucose tolerance, and reduced expression of stearoyl-CoA desaturase 1 (SCD-1). These results highlight the importance of MCH in integration of energy homeostasis downstream of leptin and, in particular, the role of MCH in regulation of energy expenditure. |
