Metformin Enhances Leptin Sensitivity in Aged Rats

ABSTRACT

To evaluate whether metformin restores leptin sensitivity in aged rats with leptin resistance, we measured leptin sensitivity in aged (2 year old) and adult (5 month old) rats after 4 weeks of treatment with metformin (300 mg/kg/D, mixing in drinking water), by measuring food intake, body weight and visceral fat losing effects. Leptin (15microgram/D) was administered by intracerobroventricular (i.c.v.) infusion through osmotic minipump for 1 week. Metformin treatment decreased body weight and daily food intake in both adult and aged rats compared with their control rats, however, these effects were more prominent in aged rats than in adult rats. Anorexic and fat losing responses following i.c.v. leptin were attenuated in aged rats compared to adult rats. However, these responses of aged rats to leptin were restored by metformin treatment. Moreover, serum concentration of leptin in aged rats was significantly decreased by combined treatment with metformin and leptin. These results suggest that metformin enhances leptin sensitivity in aged rat model, and that combination therapy with metformin and leptin would be helpful for treatment of aging-associated obesity.