title: Tauroursodeoxycholic acid inhibits TNF-α-induced lipolysis in 3T3-L1 adipocytes via the IRE-JNK-perilipin-A signaling pathway.
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.
authors.affiliation: Department of Endocrinology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China.
authors.forename: Wenyan
authors.initials: W
authors.lastname: Xia
authors.affiliation: Department of Endocrinology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China.
authors.forename: Lijing
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China.
authors.forename: Linxi
authors.initials: L
authors.lastname: Wang
authors.affiliation: Fujian Institute of Endocrinology, Fuzhou, Fujian 350001, P.R. China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China.
authors.forename: Yichuan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Endocrinology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Endocrinology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China.
authors.forename: Jianqing
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Endocrinology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China.
authors.forename: Libin
authors.initials: L
authors.lastname: Liu
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D004722:Endoribonucleases / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D066292:Lipid Droplets / Q000187:drug effects / Q000378:metabolism; D008066:Lipolysis / Q000187:drug effects*; D051379:Mice; D000070778:Perilipin-1 / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D000070778:Perilipin-1; D014409:Tumor Necrosis Factor-alpha; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine; C510185:Ern1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D004722:Endoribonucleases