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Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function
被引:1782
作者:
Uysal, KT
Wiesbrock, SM
Marino, MW
Hotamisligil, GS
机构:
[1] HARVARD UNIV,SCH PUBL HLTH,DIV BIOL SCI,BOSTON,MA 02115
[2] HARVARD UNIV,SCH PUBL HLTH,DEPT NUTR,BOSTON,MA 02115
[3] MEM SLOAN KETTERING CANC CTR,LUDWIG INST CANC RES,NEW YORK,NY 10021
来源:
关键词:
D O I:
10.1038/39335
中图分类号:
O [数理科学和化学];
P [天文学、地球科学];
Q [生物科学];
N [自然科学总论];
学科分类号:
07 ;
0710 ;
09 ;
摘要:
Obesity is highly associated with insulin resistance and is the biggest risk factor for non-insulin-dependent diabetes mellitus(1-3). The molecular basis of this common syndrome, however, is poorly understood. It has been suggested that tumour necrosis factor (TNF)-alpha is a candidate mediator of insulin resistance in obesity as it is overexpressed in the adipose tissues of rodents and humans(4-10) and it blocks the action of insulin in cultured cells and whole animals(10-14). To investigate the role of TNF-alpha in obesity and insulin resistance, we have generated obese mice with a targeted null mutation in the gene encoding TNF-alpha and those encoding the two receptors for TNF-alpha. The absence of TNF-alpha resulted in significantly improved insulin sensitivity in both diet-induced obesity and that resulting for the ob/ob model of obesity. The TNF alpha-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-alpha is an important mediator of insulin resistance in obesity through its effects on several important sites of insulin action.
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页码:610 / 614
页数:5
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