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PMID:12068289
| Citation |
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 and Matsuzawa, Y (2002) Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nat. Med. 8:731-7 |
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| Abstract |
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. |
| Links |
PubMed Online version:10.1038/nm724 |
| Keywords |
Adiponectin; Adipose Tissue/metabolism; Animals; Carrier Proteins/metabolism; Cells, Cultured; Diet; Fatty Acid-Binding Proteins; Fatty Acids, Nonesterified/blood; Fish Proteins; Insulin Receptor Substrate Proteins; Insulin Resistance/physiology; Intercellular Signaling Peptides and Proteins; Lipid Metabolism; Mice; Mice, Knockout; Myocardium/cytology; Myocardium/metabolism; Phosphatidylinositol 3-Kinases/metabolism; Phosphoproteins/metabolism; Proteins/genetics; Proteins/physiology; RNA, Messenger/genetics; Transcription, Genetic; Tumor Necrosis Factor-alpha/genetics |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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See also
References
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