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Am J Physiol Regul Integr Comp Physiol 272: R1204-R1209, 1997;
0363-6119/97 $5.00
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AJP - Regulatory, Integrative and Comparative Physiology, Vol 272, Issue 4 1204-R1209, Copyright © 1997 by American Physiological Society

ARTICLES

Leptin increases energy expenditure and selectively promotes fat metabolism in ob/ob mice

J. J. Hwa, A. B. Fawzi, M. P. Graziano, L. Ghibaudi, P. Williams, M. Van Heek, H. Davis, M. Rudinski, E. Sybertz and C. D. Strader
Department of Central Nervous System and Cardiovascular Research, Schering-Plough Research Institute, Kenilworth, New Jersey 07033, USA.

Obesity occurs whenever energy intake exceeds energy expenditure. The ob gene product leptin is a potent anorectic agent when administered to ob/ob mice, but its effects on energy expenditure have not been investigated in detail. The present study was designed to analyze the acute 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 was 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 addition, leptin had a profound effect on fuel selection: the respiratory quotient was markedly reduced, indicating a reduction in carbohydrate oxidation and an increase in fat oxidation. These acute effects of leptin on metabolic parameters are consistent with the selective loss of body fat observed on chronic leptin treatment and suggest that increased energy utilization plays an important role in the anti-obese actions of leptin.


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