Reversing adipocyte differentiation: implications for treatment of obesity.

Journal Article

Conventional treatment of obesity reduces fat in mature adipocytes but leaves them with lipogenic enzymes capable of rapid resynthesis of fat, a likely factor in treatment failure. Adenovirus-induced hyperleptinemia in normal rats results in rapid nonketotic fat loss that persists after hyperleptinemia disappears, whereas pair-fed controls regain their weight in 2 weeks. We report here that the hyperleptinemia depletes adipocyte fat while profoundly down-regulating lipogenic enzymes and their transcription factor, peroxisome proliferator-activated receptor (PPAR)gamma in epididymal fat; enzymes of fatty acid oxidation and their transcription factor, PPARalpha, normally low in adipocytes, are up-regulated, as are uncoupling proteins 1 and 2. This transformation of adipocytes from cells that store triglycerides to fatty acid-oxidizing cells is accompanied by loss of the adipocyte markers, adipocyte fatty acid-binding protein 2, tumor necrosis factor alpha, and leptin, and by the appearance of the preadipocyte marker Pref-1. These findings suggest a strategy for the treatment of obesity by alteration of the adipocyte phenotype.

Full Text

Duke Authors

Cited Authors

  • Zhou, YT; Wang, ZW; Higa, M; Newgard, CB; Unger, RH

Published Date

  • March 2, 1999

Published In

Volume / Issue

  • 96 / 5

Start / End Page

  • 2391 - 2395

PubMed ID

  • 10051652

International Standard Serial Number (ISSN)

  • 0027-8424

Language

  • eng

Conference Location

  • United States