We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Molecular mechanisms of insulin resistance and the role of the adipocyte.
- Authors
Hotamisligil, G S
- Abstract
Insulin resistance is a common feature of obesity and predisposes the affected individuals to a variety of diseases, including hypertension, dyslipidemias, cardiovascular problems and type 2 diabetes mellitus. However, the molecular mechanisms underlying abnormal insulin action and these other pathological states are not well understood. We have been focusing on cytokines, particularly TNFα and fatty acid binding proteins, as potential sites to study the molecular basis of these disorders. The role of TNFα in insulin resistance and other pathologies associated with obesity, have been examined in several experimental systems including obese mice with homozygous null mutations at the TNFα or TNF receptor loci. Analysis of these animals demonstrated that the genetic absence of TNF signaling in obesity: (i) significantly improves insulin receptor signaling capacity and consequently insulin sensitivity; (ii) prevents brown adipose tissue atrophy and β[SUB3]-adrenoreceptor deficiency and improves thermo-adaptive responses, (iii) decreases the) elevated PAI-1 and TGFβ production; and (iv) lowers hyperlipidemia and hyperleptinemia. Hence, abnormal TNFα action in adipocytes disturbs many aspects of metabolic homeostasis in obesity.
- Subjects
INSULIN resistance; FAT cells; TUMOR necrosis factors; TRANSGENIC mice
- Publication
International Journal of Obesity & Related Metabolic Disorders, 2000, Vol 24, pS23
- ISSN
0307-0565
- Publication type
Article
- DOI
10.1038/sj.ijo.0801497