Protection from obesity-induced insulin resistance in mice lacking TNF-α function

K. Teoman Uysal, Sarah M. Wiesbrock, Michael W. Marino and Gkhan S. Hotamisligil ()
Additional contact information
K. Teoman Uysal: Harvard School of Public Health
Sarah M. Wiesbrock: Harvard School of Public Health
Michael W. Marino: Ludwig Institute for Cancer Research, Memorial Sloan Kettering Cancer Center
Gkhan S. Hotamisligil: Harvard School of Public Health

Nature, 1997, vol. 389, issue 6651, 610-614

Abstract: Abstract Obesity is highly associated with insulin resistance and is the biggest risk factor for non-insulin-dependent diabetes mellitus1,2,3. 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 humans4,5,6,7,8,9,10 and it blocks the action of insulin in cultured cells and whole animals10,11,12,13,14. 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.

Date: 1997
References: Add references at CitEc
Citations: View citations in EconPapers (5)

Downloads: (external link)
https://www.nature.com/articles/39335 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:389:y:1997:i:6651:d:10.1038_39335

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/39335

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().