Multilevel regulation of leptin storage, turnover, and secretion by feeding and insulin in rat adipose tissue.
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 [(35)S]methionine/cysteine incorporation into immunoprecipitable leptin. Insulin in vitro did not acutely increase leptin biosynthesis or rates of (125)I-leptin degradation. Pulse-chase studies showed that in adipose tissue from fed but not starved rats, insulin accelerated the secretion of [(35)S]leptin by approximately 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.
Lee
Mi-Jeong
MJ
Department of Nutritional Sciences, Rutgers, the State University of New Jersey, New Brunswick, NJ 08901, USA.
Fried
Susan K
SK
D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D015152:Blotting, Northern / Q000379:methods; D001835:Body Weight; D002738:Chloroquine / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D007456:Iodine Isotopes; D020738:Leptin / Q000235:genetics / Q000378:metabolism*; D007976:Leupeptins / Q000494:pharmacology; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013217:Starvation; D013460:Sulfur Isotopes
D007328:Insulin; D007456:Iodine Isotopes; D020738:Leptin; D007976:Leupeptins; D012333:RNA, Messenger; D013460:Sulfur Isotopes; D002738:Chloroquine; D003513:Cycloheximide; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde