Aging is associated with resistance to effects of leptin on fat distribution and insulin action

Leptin has been shown to modulate total body fat and visceral fat distribution and to enhance insulin action in young rats. We hypothesize that failure of leptin action may contribute to the increase in visceral fat and insulin resistance in aging. By chronic subcutaneous infusion of leptin over 7 days, we increased leptin levels in young rats to match the levels in aging ad libitum fed rats. Leptin induced an approximately 50% decrease in food intake compared with saline controls, an approximately 50% decrease in visceral fat, and improved hepatic (fourfold) and peripheral (30%) insulin action (euglycemic hyperinsulinemic clamp technique) compared with the pair-fed group (p