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Am J Physiol Regul Integr Comp Physiol 286: R756-R763, 2004. First published December 4, 2003; doi:10.1152/ajpregu.00508.2002
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APPETITE, OBESITY AND METABOLISM

Feeding and temperature responses to intravenous leptin infusion are differential predictors of obesity in rats

Marie-Pierre Ruffin,1 Tiziana Adage,1 Folkert Kuipers,2 Jan H. Strubbe,1 Anton J. W. Scheurink,1 and Gertjan van Dijk1

1Department of Animal Physiology, Division Neuroendocrinology, University of Groningen, 9750 AA Haren and 2Department of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University Hospital, 9713 GZ Groningen, The Netherlands

Submitted 21 August 2002 ; accepted in final form 1 December 2003

Obesity is frequently associated with leptin resistance. The present study investigated whether leptin resistance in rats is present before obesity develops, and thus could underlie obesity induced by 16 wk exposure to a liquid, palatable, high-energy diet (HED). Before HED exposure, male Wistar rats (weighing between 330 and 360 g) received intravenous infusions of 20 µg leptin 2 h before dark (~57 µg/kg rat). Relative to saline infusion, this caused a highly variable effect on food intake (ranging between -94 and +129%), with food intake suppression that appeared negatively correlated with HED-induced increases in body weight gain, caloric intake, adiposity, and plasma leptin levels. In contrast, leptin's thermogenic response was positively correlated to body weight gain linked to weights of viscera, but not to adiposity. Before HED exposure, leptin unexpectedly increased food intake in some rats (fi+, n = 8), whereas others displayed the normal reduction in food intake (fi-, n = 7). HED-exposed fi+ rats had higher plasma leptin levels, retroperitoneal fat pad weight, HED intake, and body weight gain than fi- and chow-fed rats. These parameters were also higher in HED-exposed fi- rats relative to chow rats, except for plasma leptin concentrations. It is concluded that leptin's reduced efficacy to suppress food intake could predict obesity on an HED. An unexpected orexigenic effect of leptin might potentially contribute to this as well.

leptin; obesity; thermogenesis; hypothalamus; diet


Address for reprint requests and other correspondence: G. van Dijk, Dept. of Animal Physiology, Univ. of Groningen, P. O. Box 14, 9750 AA Haren, The Netherlands (E-mail: g.van.dijk{at}biol.rug.nl).




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Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2005; 288(6): R1438 - R1443.
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