期刊
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
卷 36, 期 4, 页码 1499-1516出版社
KARGER
DOI: 10.1159/000430314
关键词
Adipogenesis; Inflammation; Insulin receptor; Insulin-stimulated glucose uptake; DNA methylation; 3T3-L1
资金
- CIBERobn
- Nutrigenio project (MINECO, Spain)
- Linea Especial Nutrition, Obesity and Health of the University of Navarra [LE/97]
- Asociacion de Amigos of the University of Navarra
Background/Aims: Tumor necrosis factor-alpha (TNF-alpha)-mediated chronic low-grade inflammation of adipose tissue is associated with obesity and insulin resistance. Caveolin-1 (Cav-1) is the central component of adipocyte caveolae and has an essential role in the regulation of insulin signaling. The effects of TNF-alpha on Cav-1 expression and insulin signaling during adipocyte differentiation and in mature adipocytes were studied. Methods: 3T3-L1 cells were differentiated (21 days) in the presence TNF-alpha (10 ng/mL) and mature adipocytes were also treated with TNF-alpha for 48 hours. Cav-1 and insulin receptor (IR) gene methylation were determined as well as Cav-1, IR, PKB/AKT-2 and Glut-4 expression and activation by real time RT-PCR and western blot. Baseline and insulin-induced glucose uptake was measured by the 2-[C-14]-deoxyglucose uptake assay. Results: TNF-alpha slowed down the differentiation program, hindering the expression of some insulin signaling intermediates without fully eliminating insulin-mediated glucose uptake. In mature adipocytes, TNF-alpha did not compromise lipidstorage capacity, but downregulated the expression of the insulin signaling intermediates, totally blocking insulin-mediated glucose uptake. Insulin sensitivity correlated with the level of activated phospho-Cav-1 in both situations, strongly suggesting the direct contribution of Cav-1 to the maintenance of this physiological response. Conclusion: Cav-1 activation by phosphorylation seems to be essential for the maintenance of an active and insulin-sensitive glucose uptake. Copyright (C) 2015 S. Karger AG, Basel
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