Protection from obesity-induced insulin resistance in mice lacking TNF-α function Journal Article
| Authors: | Uysal, K. T.; Wiesbrock, S. M.; Marino, M. W.; Hotamisligil, G. S. |
| Article Title: | Protection from obesity-induced insulin resistance in mice lacking TNF-α function |
| Abstract: | Obesity is highly associated with insulin resistance and is the biggest risk factor for non-insulin-dependent diabetes mellitus. The molecular basis of this common syndrome however, is poorly understood. It has been suggested that tumour necrosis factor (TNF)-α is a candidate mediator of insulin resistance in obesity, as it is overexpressed in the adipose tissues of rodents and humans and it blocks the action of insulin in cultured cells and whole animals. To investigate the role of TNF-α in obesity and insulin resistance, we have generated obese mice with a targeted null mutation in the gene encoding TNF-α and those encoding the two receptors for TNF-α. The absence of TNF-α resulted in significantly improved insulin sensitivity in both diet-induced obesity and that resulting for the ob/ob model of obesity. The TNFα-deficient obese mice had lower levels of circulating free fatty acids, and were protected from the obesity-related reduction in the insulin receptor signalling in muscle and fat tissues. These results indicate that TNF-α is an important mediator of insulin resistance in obesity through its effects on several important sites of insulin action. |
| Keywords: | signal transduction; controlled study; gene mutation; mutation; nonhuman; mouse; animals; mice; animal tissue; animal experiment; animal model; obesity; phosphorylation; mice, inbred c57bl; animalia; tumor necrosis factor alpha; tumor necrosis factor-alpha; glucose; insulin resistance; fatty acids; tumor necrosis factor receptor; rodentia; homeostasis; fatty acid; glucose tolerance test; adipose tissue; triglycerides; receptors, tumor necrosis factor; insulin receptor; muscle proteins; glucose transporter type 4; monosaccharide transport proteins; male; priority journal; article; receptor, insulin; mice, obese; fatty acid blood level |
| Journal Title: | Nature |
| Volume: | 389 |
| Issue: | 6651 |
| ISSN: | 0028-0836 |
| Publisher: | Nature Publishing Group |
| Date Published: | 1997-10-09 |
| Start Page: | 610 |
| End Page: | 614 |
| Language: | English |
| DOI: | 10.1038/39335 |
| PUBMED: | 9335502 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 17 March 2017 -- Source: Scopus |
