[Leptin-induced regulation of fat metabolism and its accumulation]

Recent findings have shown that supplementation of leptin decreases body weight in leptin-deficient ob/ob mice through its suppressive effect on food intake and accelerating effect on energy expenditure, particularly on peripheral fat lipolysis. When endogenously hyperleptinemic obese rats were further induced to be hyperleptinemic exogeously using adenovirus vector, their body fat mass was reduced but not food intake. These findings implicate a direct lipolytic action of leptin on peripheral adipose tissues in obese rats because leptin transport capacity across the blood-brain barrier is almost saturated by the relative hyperleptinemia. Recovery from excessive body fat accumulation after adenovirus-induced hyperleptinemia is much slower than that after caloric restriction because there may be difference between those treatments in decreased lipogenic enzymes activities and/or increased activities of fatty acid oxidative enzymes and thermogenic uncoupling proteins. The fat melting effects of leptin may show its crucial pharmacologic potencies to design therapeutic strategies against morbid obesity. The studies on leptin provide a better understanding for creative approaches to anti-obesity drug that are efficient for reducing body fat mass without harmful side-effects.