LEPTIN INCREASES ENERGY-EXPENDITURE AND SELECTIVELY PROMOTES FAT-METABOLISM IN OB OB MICE/

Obesity occurs whenever energy intake exceeds energy expenditure. The ob gene product leptin is a potent anorectic agent when administered t o ob lob mice, but its effects on energy expenditure have not been inv estigated in detail. The present study was designed to analyze the acu te metabolic effects of leptin in vivo. Analysis of oxygen consumption in ob/ob mice demonstrated a reduction in energy expenditure compared with lean controls; this reduction showed a diurnal fluctuation and w as most evident during the light cycle. A single intraperitoneal dose of leptin increased oxygen consumption during the light cycle in ob/ob mice, ablating the circadian fluctuation in this parameter. In additi on, leptin had a profound effect on fuel selection: the respiratory qu otient was markedly reduced, indicating a reduction in carbohydrate ox idation and an increase in fat oxidation. These acute effects of lepti n on metabolic parameters are consistent with the selective loss of bo dy fat observed on chronic leptin treatment and suggest that increased energy utilization plays an important role in the anti-obese actions of leptin.