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Reversing adipocyte differentiation: implications for treatment of obesity.

Publication ,  Journal Article
Zhou, YT; Wang, ZW; Higa, M; Newgard, CB; Unger, RH
Published in: Proc Natl Acad Sci U S A
March 2, 1999

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.

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Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

March 2, 1999

Volume

96

Issue

5

Start / End Page

2391 / 2395

Location

United States

Related Subject Headings

  • Triglycerides
  • Transcription Factors
  • Recombinant Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Rats, Zucker
  • Rats
  • Proteins
  • Protein Biosynthesis
  • Obesity
  • Male
 

Citation

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Zhou, Y. T., Wang, Z. W., Higa, M., Newgard, C. B., & Unger, R. H. (1999). Reversing adipocyte differentiation: implications for treatment of obesity. Proc Natl Acad Sci U S A, 96(5), 2391–2395. https://doi.org/10.1073/pnas.96.5.2391
Zhou, Y. T., Z. W. Wang, M. Higa, C. B. Newgard, and R. H. Unger. “Reversing adipocyte differentiation: implications for treatment of obesity.Proc Natl Acad Sci U S A 96, no. 5 (March 2, 1999): 2391–95. https://doi.org/10.1073/pnas.96.5.2391.
Zhou YT, Wang ZW, Higa M, Newgard CB, Unger RH. Reversing adipocyte differentiation: implications for treatment of obesity. Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2391–5.
Zhou, Y. T., et al. “Reversing adipocyte differentiation: implications for treatment of obesity.Proc Natl Acad Sci U S A, vol. 96, no. 5, Mar. 1999, pp. 2391–95. Pubmed, doi:10.1073/pnas.96.5.2391.
Zhou YT, Wang ZW, Higa M, Newgard CB, Unger RH. Reversing adipocyte differentiation: implications for treatment of obesity. Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2391–2395.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

March 2, 1999

Volume

96

Issue

5

Start / End Page

2391 / 2395

Location

United States

Related Subject Headings

  • Triglycerides
  • Transcription Factors
  • Recombinant Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Rats, Zucker
  • Rats
  • Proteins
  • Protein Biosynthesis
  • Obesity
  • Male