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Disappearance of body fat in normal rats induced by adenovirus-mediated leptin gene therapy.

Sustained hyperleptinemia of 8 ng/ml was induced for 28 days in normal Wistar rats by infusing a recombinant adenovirus containing the rat leptin cDNA (AdCMV-leptin). Hyperleptinemic rats exhibited a 30-50% reduction in food intake and gained only 22 g over the experimental period versus 115-132 g in control animals that received saline infusions or a recombinant virus containing the beta-galactosidase gene (AdCMV-beta Gal). Body fat was absent in hyperleptinemic rats, whereas control rats pair-fed to the hyperleptinemic rats retained approximately 50% body fat. Further, plasma triglycerides and insulin levels were significantly lower in hyperleptinemic versus pair-fed controls, while fatty acid and glucose levels were similar in the two groups, suggestive of enhanced insulin sensitivity in the hyperleptinemic animals. Thus, despite equivalent reductions in food intake and weight gain in hyperleptinemic and pair-fed animals, identifiable fat tissue was completely ablated only in the former group, raising the possibility of a specific lipoatrophic activity for leptin.

Pubmed ID: 8962134

Authors

  • Chen G
  • Koyama K
  • Yuan X
  • Lee Y
  • Zhou YT
  • O'Doherty R
  • Newgard CB
  • Unger RH

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Data

December 10, 1996

Associated Grants

  • Agency: NIDDK NIH HHS, Id: DK02700-37
  • Agency: PHS HHS, Id: P50H2598801

Mesh Terms

  • Adenoviridae
  • Animals
  • Gene Transfer Techniques
  • Genetic Therapy
  • Genetic Vectors
  • Leptin
  • Obesity
  • Proteins
  • Rats
  • Rats, Wistar