Tauroursodeoxycholic acid inhibits TNF-α-induced lipolysis in 3T3-L1 adipocytes via the IRE-JNK-perilipin-A signaling pathway

牛磺熊去氧胆酸通过 IRE-JNK-perilipin-A 信号通路抑制 TNF-α 诱导的 3T3-L1 脂肪细胞脂肪分解

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作者:Wenyan Xia, Yu Zhou, Lijing Wang, Linxi Wang, Xiaoying Liu, Yichuan Lin, Qing Zhou, Jianqing Huang, Libin Liu

Abstract

The present study investigated the effects of tauroursodeoxycholic acid (TUDCA) on the lipolytic action of tumor necrosis factor (TNF)-α in 3T3-L1 adipocytes. Following treatment with TNF‑α, cell viability was determined by MTT assay to select the optimum concentration and duration of TNF‑α treatment in 3T3‑L1 adipocytes. Intracellular lipid droplet dispersion and glycerin content in culture media were determined to evaluate the effect of TUDCA on TNF‑α‑induced lipolysis in 3T3‑L1 adipocytes. Western blotting was performed to detect protein expression levels of perilipin‑A and protein markers of endoplasmic reticulum stress: Immunoglobulin‑binding protein (BiP), inositol‑requiring enzyme (IRE), c‑Jun N‑terminal kinase (JNK), phosphorylated (p)‑IRE and p‑JNK. Following treatment with 50 ng/ml TNF‑α for 24 h, glycerin content increased significantly and lipid droplets were dispersed. Glycerin content was reduced significantly and dispersal of lipid droplets reduced following pretreatment of 3T3‑L1 adipocytes with 1 mmol/l TUDCA. TNF‑α additionally activated the expression of BiP, p‑IRE and p‑JNK in a time‑dependent manner; following pretreatment of 3T3‑L1 adipocytes with 1 mmol/l TUDCA, the expression levels of these three proteins decreased. Therefore, TUDCA may inhibit TNF-α-induced lipolysis in 3T3‑L1 adipocytes and reduce production of free fatty acids. Its underlying molecular mechanisms are potentially associated with the inhibition of activation of the IRE‑JNK signaling pathway, which influences perilipin-A expression levels.

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