Objectives: 

The purpose of this study is to characterize the functional role of myostatin (GDF-8) in the regulation of food intake, energy homeostasis, and reproductive function in mice.

Materials: 

Studies were conducted in both male and female adult myostatin- knockout mice (Mstn-/-). Body composition was evaluated in live conscious animals by quantitative nuclear magnetic resonance spectroscopy. Plasma leptin levels were determined by mouse-specific leptin ELISA. The determination of hypothalamic neuropeptides was performed by in situ hybridization. The expression of leptin receptor in liver and hypothalamus was quantified by RT-PCR. Fertility test were performed by placing individual Mstn-/- male or female with either male or female Mstn-/- or wild-type mice. Vaginal opening was observed in the female knockout mice after weaning, and vaginal smears were performed to assess estrous cycle. Hypothalamic GnRH expression was studied by RT-PCR. Statistical analysis were performed with non-parametric test.

Results: 

Mstn-/- mice displayed an increased lean body mass and significantly reduced fat deposits. Food intake and hypothalamic expression of NPY and AgRP showed no increased despite hypoleptinemia in Mstn-/- ; while hypothalamic POMC, MCH and orexin were decreased. The expression of leptin receptor b was increased in liver of Mstn-/- mice. Vaginal opening was delayed in Mstn-/- female mice. Fertility was also decreased in Mstn-/- , mostly in female.

Conclusions: 

The myostatin-deficient mice have increased leptin sensitivity and altered reproductive function.