Hyperleptinemia depletes fat from denervated fat tissue

Adenovirus-mediated transfer of the leptin gene causes severe hyperleptinemia with rapid disappearance of visible body fat. To determine if this dramatic lipopenic action is mediated by neurotransmitted signals from the central nervous system, we transplanted the right epididymal fat pad of normal rats to the anterior abdominal wall. Four weeks later, rats were infused with either adenovirus-leptin cDNA (AdCMV-leptin) or adenovirus-β-galactosidase (AdCMV-β-gal). Eight days later, plasma leptin averaged 23 ± 12 ng/ml in the former and 1.2 ± 0.4 ng/ml in the latter. The fat transplant was intact in all 4 AdCMV-β-gal-infused rats but had disappeared in all 4 hyperleptinemic rats. Tyrosine hydroxylase staining of the fat pad remnant was negative, excluding regrowth of sympathetic nerves. Thus, the lipopenic action of severe hyperleptinemia on adipocytes is not mediated by neurotransmitters, but must have resulted either from direct action of leptin and/or from leptin-mediated neurohormones.