Leptin inhibits prehibernation hyperphagia and reduces body weight in arctic ground squirrels.

The ob gene product leptin is thought to play a physiological role in the fine tuning of a homeostatic mechanism regulating satiety and adiposity. Mouse recombinant leptin was administered to seasonally hyperphagic arctic ground squirrels as a first step in demonstrating the evolutionary conservation of leptin function and the potential involvement of leptin in the seasonal regulation of adiposity in hibernators. Continuous infusion of leptin for 3 wk via miniosmotic pumps resulted in a reduction in food intake and body weight in a manner consistent with its proposed role as a satiety hormone. During the recovery period after leptin administration, squirrels that had received leptin became hyperphagic relative to controls. Percent body fat was estimated at weekly intervals by measuring total body electrical conductivity and decreased after 3 wk of leptin administration. Our observations support the role of leptin as a regulatory hormone involved in the control of satiety, adiposity, and possibly energy expenditure in hibernating mammals.