Hyperleptinemia depletes fat from denervated fat tissue

Adenovirus-mediated transfer of the leptin gene causes severe hyperleptinem ia with rapid disappearance of visible body fat, To determine if this drama tic lipopenic action is mediated by neurotransmitted signals from the centr al nervous system, we transplanted the right epididymal fat pad of normal r ats to the anterior abdominal wall. Four weeks later, rats were infused wit h either adenovirus-leptin cDNA (AdCMV-leptin) or adenovirus-beta-galactosi dase (AdCMV-beta-gal). Eight days later, plasma leptin averaged 23 +/- 12 n g/ml in the former and 1.2 +/- 0.4 ng/ml in the latter. The fat transplant was intact in all 4 AdCMV-beta-gal-infused rats but had disappeared in all 4 hyperleptinemic rats. Tyrosine hydroxylase staining of the fat pad remnan t was negative, excluding regrowth of sympathetic nerves. Thus, the lipopen ic action of severe hyperleptinemia on adipocytes is not mediated by neurot ransmitters, but must have resulted either from direct action of leptin and /or from leptin-mediated neurohormones. (C) 1999 Academic Press.