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Journal of Lipid Research, Vol. 47, 1984-1993, September 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Multilevel regulation of leptin storage, turnover, and secretion by feeding and insulin in rat adipose tissue

Mi-Jeong Lee^* and Susan K. Fried^,1

^* Department of Nutritional Sciences, Rutgers, the State University of New Jersey, New Brunswick, NJ 08901
Divisions of Endocrinology, Diabetes and Nutrition, School of Medicine, University of Maryland, Baltimore, MD 21201

Published, JLR Papers in Press, May 31, 2006.

¹ To whom correspondence should be addressed. e-mail: sfried{at}medicine.umaryland.edu

The mechanisms of the increased serum leptin in response to feeding are poorly understood. Therefore, we used metabolic labeling to directly assess leptin biosynthesis, secretion, and turnover in adipose tissue from 14 h-starved compared with fed 12–14 week old rats. Starvation decreased serum leptin (–47 ± 7%), adipose tissue leptin content (–32 ± 5%), and leptin secretion during 3 h of incubation (–65 ± 12%). Starvation did not affect leptin mRNA levels but decreased rates of leptin biosynthesis by tissue fragments, as determined by [³⁵S]methionine/cysteine incorporation into immunoprecipitable leptin. Insulin in vitro did not acutely increase leptin biosynthesis or rates of ¹²⁵I-leptin degradation. Pulse-chase studies showed that in adipose tissue from fed but not starved rats, insulin accelerated the secretion of [³⁵S]leptin by 2-fold after 30 and 60 min of chase. Degradation of newly synthesized leptin was slower in adipose tissue of starved than fed rats (half-lives of 50 and 150 min, respectively). Inhibitor experiments showed that both lysosomes and proteosomes contributed to leptin degradation. In conclusion, feeding compared with starvation influences leptin production at multiple posttranscriptional levels: synthesis, tissue storage, turnover, and secretion. The insulin-stimulated release of leptin from a preformed intracellular leptin pool may contribute to increases in serum leptin levels after meals.

Supplementary key words degradation • lipoprotein lipase • proteosome • lysosome • starvation • translation

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