Leptin increases energy expenditure and selectively promotes fat
metabolism in ob/ob mice.
Hwa, Joyce J., Ahmad B. Fawzi, Michael P. Graziano, Lorraine Ghibaudi,
Patricia Williams, Margaret Van Heek, Harry Davis, Mark Rudinski,
Edmund Sybertz, and Catherine D. Strader.
Department of CNS and Cardiovascular Research, Schering-Plough
Research Institute, Kenilworth, New Jersey 07033
APStracts 3:0421R, 1996.
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 to 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 upon chronic leptin treatment and suggest that increased
energy utilization plays an important role in the anti-obese actions
of leptin.
Received 8 August 1996; accepted in final form 5 November 1996.
APS Manuscript Number R468-6.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996