Combined leptin actions on adipose tissue and hypothalamus are required to deplete adipocyte fat in lean rats: Implications for obesity treatment

Byung Hyun Park, May-Yun Wang, Young H Lee, Xinxin Yu, Mariella Ravazzola, Lelio Orci, Roger H Unger

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22 Scopus citations


Intense hyperleptinemia completely depletes adipocyte fat of normal rats within 14 days. To determine the mechanism, epididymal fat pads from normal wild-type (+/+) and obese (fa/fa) Zucker Diabetic Fatty (ZDF) donor rats were transplanted into normal +/+ and fa/fa ZDF recipients. Hyperleptinemia induced by adenovirus-leptin administration depleted all fat from native fat pads and from fat transplants from +/+ donors but not from transplants from ZDF fa/fa donors with defective leptin receptors. In both native and transplanted +/+ fat pads, large numbers of mitochondria were apparent, and genes involved in fatty acid oxidation were up-regulated. However, +/+ fat pads transplanted into fa/fa recipients did not respond to hyperleptinemia, suggesting lack of an essential leptin-stimulated cohormone(s). In +/+ but not in fa/fa rats, plasma catecholamine levels rose, and both P-STAT3 and P-CREB increased in adipose tissue, suggesting that both direct and indirect (hypothalamic) leptin receptor-mediated actions of hyperleptinemia are involved in depletion of adipocyte fat.

Original languageEnglish (US)
Pages (from-to)40283-40291
Number of pages9
JournalJournal of Biological Chemistry
Issue number52
Publication statusPublished - Dec 29 2006


ASJC Scopus subject areas

  • Biochemistry

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