Reversing adipocyte differentiation: Implications for treatment of obesity

Yan Ting Zhou, Zhuo Wei Wang, Moritake Higa, Christopher B. Newgard, Roger H Unger

Research output: Contribution to journalArticle

198 Citations (Scopus)

Abstract

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)γ in epididymal fat; enzymes of fatty acid oxidation and their transcription factor, PPARα, 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 α, 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.

Original languageEnglish (US)
Pages (from-to)2391-2395
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number5
DOIs
StatePublished - Mar 2 1999

Fingerprint

Adipocytes
Obesity
Fats
Peroxisome Proliferator-Activated Receptors
Transcription Factors
Enzymes
Fatty Acids
Fatty Acid-Binding Proteins
Leptin
Treatment Failure
Adenoviridae
Triglycerides
Tumor Necrosis Factor-alpha
Phenotype
Weights and Measures

Keywords

  • Dedifferentiation
  • Leptin
  • Lipogenesis
  • Oxidation
  • Post-adipocyte

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Reversing adipocyte differentiation : Implications for treatment of obesity. / Zhou, Yan Ting; Wang, Zhuo Wei; Higa, Moritake; Newgard, Christopher B.; Unger, Roger H.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 96, No. 5, 02.03.1999, p. 2391-2395.

Research output: Contribution to journalArticle

Zhou, Yan Ting ; Wang, Zhuo Wei ; Higa, Moritake ; Newgard, Christopher B. ; Unger, Roger H. / Reversing adipocyte differentiation : Implications for treatment of obesity. In: Proceedings of the National Academy of Sciences of the United States of America. 1999 ; Vol. 96, No. 5. pp. 2391-2395.
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