出版社：American Society for Biochemistry and Molecular Biology
摘要：The mechanisms of the increased serum leptin in response tofeeding are poorly understood. Therefore, we used metaboliclabeling to directly assess leptin biosynthesis, secretion,and turnover in adipose tissue from 14 h-starved compared withfed 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 mRNAlevels but decreased rates of leptin biosynthesis by tissuefragments, as determined by [35S]methionine/cysteine incorporationinto immunoprecipitable leptin. Insulin in vitro did not acutelyincrease leptin biosynthesis or rates of 125I-leptin degradation.Pulse-chase studies showed that in adipose tissue from fed butnot starved rats, insulin accelerated the secretion of [35S]leptinby 2-fold after 30 and 60 min of chase. Degradation of newlysynthesized leptin was slower in adipose tissue of starved thanfed rats (half-lives of 50 and 150 min, respectively). Inhibitorexperiments showed that both lysosomes and proteosomes contributedto leptin degradation. In conclusion, feeding compared withstarvation influences leptin production at multiple posttranscriptionallevels: synthesis, tissue storage, turnover, and secretion.The insulin-stimulated release of leptin from a preformed intracellularleptin pool may contribute to increases in serum leptin levelsafter meals.Supplementary key words degradation • lipoprotein lipase • proteosome • lysosome • starvation • translation
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
