Transmembrane tumor necrosis factor-alpha sensitizes adipocytes to insulin

Publication date: 5 May 2015 Source:Molecular and Cellular Endocrinology, Volume 406 Author(s): Wenjing Zhou , Peng Yang , Li Liu , Shan Zheng , Qingling Zeng , Huifang Liang , Yazhen Zhu , Zunyue Zhang , Jing Wang , Bingjiao Yin , Feili Gong , Yiping Wu , Zhuoya Li Transmembrane TNF-α (tmTNF-α) acts both as a ligand, delivering ‘forward signaling’ via TNFR, and as a receptor, transducing ‘reverse signaling’. The contradiction of available data regarding the effect of tmTNF-α on insulin resistance may be due to imbalance in both signals. Here, we demonstrated that high glucose-induced impairment of insulin-stimulated glucose uptake by 3T3-L1 adipocytes was concomitant with decreased tmTNF-α expression and increased soluble TNF-α (sTNF-α) secretion. However, when TACE was inhibited, preventing the conversion of tmTNF-α to sTNF-α, this insulin resistance was partially reversed, indicating a salutary role of tmTNF-α. Treatment of 3T3-L1 adipocytes with exogenous tmTNF-α promoted insulin-induced phosphorylation of IRS-1 and Akt, facilitated GLUT4 expression and membrane translocation, and increased glucose uptake while addition of sTNF-α resulted in the opposite effect. Furthermore, tmTNF-α downregulated the production of IL-6 and MCP-1 via NF-κB inactivation, as silencing of A20, an inhibitor for NF-κB, by siRNA, abolished this effect of tmTNF-α. However, tmTNF-α upregulated adiponectin expression through the PPAR-γ pathway, as inhibitio...
Source: Molecular and Cellular Endocrinology - Category: Endocrinology Source Type: research