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Diet-induced insulin resistance in mice lacking adiponectin/ACRP30.

Here we investigated the biological functions of adiponectin/ACRP30, a fat-derived hormone, by disrupting the gene that encodes it in mice. Adiponectin/ACRP30-knockout (KO) mice showed delayed clearance of free fatty acid in plasma, low levels of fatty-acid transport protein 1 (FATP-1) mRNA in muscle, high levels of tumor necrosis factor-alpha (TNF-alpha) mRNA in adipose tissue and high plasma TNF-alpha concentrations. The KO mice exhibited severe diet-induced insulin resistance with reduced insulin-receptor substrate 1 (IRS-1)-associated phosphatidylinositol 3 kinase (PI3-kinase) activity in muscle. Viral mediated adiponectin/ACRP30 expression in KO mice reversed the reduction of FATP-1 mRNA, the increase of adipose TNF-alpha mRNA and the diet-induced insulin resistance. In cultured myocytes, TNF-alpha decreased FATP-1 mRNA, IRS-1-associated PI3-kinase activity and glucose uptake, whereas adiponectin increased these parameters. Our results indicate that adiponectin/ACRP30 deficiency and high TNF-alpha levels in KO mice reduced muscle FATP-1 mRNA and IRS-1-mediated insulin signaling, resulting in severe diet-induced insulin resistance.

Pubmed ID: 12068289


  • Maeda N
  • Shimomura I
  • Kishida K
  • Nishizawa H
  • Matsuda M
  • Nagaretani H
  • Furuyama N
  • Kondo H
  • Takahashi M
  • Arita Y
  • Komuro R
  • Ouchi N
  • Kihara S
  • Tochino Y
  • Okutomi K
  • Horie M
  • Takeda S
  • Aoyama T
  • Funahashi T
  • Matsuzawa Y


Nature medicine

Publication Data

July 1, 2002

Associated Grants


Mesh Terms

  • Adiponectin
  • Adipose Tissue
  • Animals
  • Carrier Proteins
  • Cells, Cultured
  • Diet
  • Fatty Acid-Binding Proteins
  • Fatty Acids, Nonesterified
  • Fish Proteins
  • Insulin Receptor Substrate Proteins
  • Insulin Resistance
  • Intercellular Signaling Peptides and Proteins
  • Lipid Metabolism
  • Mice
  • Mice, Knockout
  • Myocardium
  • Phosphatidylinositol 3-Kinases
  • Phosphoproteins
  • Proteins
  • RNA, Messenger
  • Transcription, Genetic
  • Tumor Necrosis Factor-alpha