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- Hotamisligil, GS, et al.
(författare)
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Differential regulation of the p80 tumor necrosis factor receptor in human obesity and insulin resistance
- 1997
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 46:3, s. 451-455
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have shown that tumor necrosis factor (TNF)-α production from adipose tissue is elevated in rodent and human obesity and plays an important role in insulin resistance in experimental animal models. In this study, we examined the adipose expression of both TNF receptors (TNFR1 and TNFR2) in human obesity and demonstrated that obese female subjects express approximately twofold more TNFR2 mRNA in fat tissue and approximately sixfold more soluble TNFR2 in circulation relative to lean control subjects. In contrast, TNFR1 expression and protein levels were similar in these subjects. TNFR2 expression levels in adipose tissue were strongly correlated with BMI (r = 0.65, P < 0.001) and level of hyperinsulinemia (P < 0.001), an indirect measure of insulin resistance, as well as level of TNF-α mRNA expression in fat tissue (r = 0.56, P < 0.001). These results suggest that TNFR2 might play a role in human obesity by modulating the actions of TNF-α.
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- Xu, HY, et al.
(författare)
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Altered tumor necrosis factor-alpha (TNF-alpha) processing in adipocytes and increased expression of transmembrane TNF-alpha in obesity
- 2002
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 51:6, s. 1876-1883
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Tidskriftsartikel (refereegranskat)abstract
- Tumor necrosis factor-α (TNF-α) is synthesized as a 26-kDa transmembrane protein (mTNF-α), which may present on the cell surface or be processed to release the 17-kDa soluble form (sTNF-α). Because regulation of this ectodomain shedding might be critical in the generation of systemic versus local cytokine responses, we examined the rate of mTNF-α processing in adipocytes and its regulation in obesity. Here, we demonstrate that the 26-kDa mTNF-α is present in adipose tissue and that its production is significantly increased in different rodent obesity models as well as in obese humans. There was no apparent deficiency in the level of the major TNF-α converting enzyme in adipose tissue to account for the excess amount of mTNF-α produced in obesity. However, experiments in cultured fat cells stably expressing TNF-α demonstrated a significantly decreased rate of TNF-α cleavage in differentiated adipocytes compared with preadipocytes. Thus, a decreased processing rate of mTNF-α in mature adipocytes combined with an increase in TNF-α production may be a potential mechanism resulting in elevated membrane-associated TNF-α in adipose tissue in obesity.
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