Slow recovery of body fat lost during adenovirus-induced hyperleptinemia

In normal rats, adenovirus-induced hyperleptinemia causes disappearance of visible body fat, down-regulation of lipogenic enzymes, and upregulation of oxidative enzymes and thermogenic proteins. In addition, preadipocyte mark ers replace mature adipocyte markers, suggesting dedifferentiation. In weig ht loss induced by caloric restriction, by contrast, the lipogenic machiner y is essentially intact. To determine if the radical changes induced by lep tin would slow the reappearance of body fat, we compared normal lean rats m ade hyperleptinemic by infusing an adenovirusleptin construct with diet-mat ched littermates. Initially, in plasma leptin the hyperleptinemic rats aver aged similar to 50x the controls and, although it declined progressively, i t was still slightly elevated at 150 days (P < 0.05). In the hyperleptinemi cs, body fat mass, quantified by magnetic resonance spectroscopy, remained below the pretreatment value for 60 days, while in diet-matched controls it exceeded the pretreatment value. Epididymal fat pad weight in hyperleptine mics was still 28% below paired controls at 150 days posttreatment. Histolo gic examination revealed adipocytes of hyperleptinemic animals to be smalle r GO days after treatment. At 60 days, adipose tissue UCP-2 gene expression in hyperleptinemics was still above controls, but expression of other lipo genic and oxidative enzymes had returned to baseline expression levels. We conclude that in normal rats recovery of body fat following adenovirus indu ced hyperleptinemia is much slower than after caloric restriction, possibly because of persistent upregulation of adipocyte UCP-2. (C) 2000 Academic P ress.