title: Alpha-lipoic acid attenuates endoplasmic reticulum stress-induced insulin resistance by improving mitochondrial function in HepG2 cells.
abstract: Alpha-lipoic acid (ALA) has been reported to have beneficial effects for improving insulin sensitivity. However, the underlying molecular mechanism of the beneficial effects remains poorly understood. Endoplasmic reticulum (ER) stress and mitochondrial dysfunction are considered causal factors that induce insulin resistance. In this study, we investigated the effect of ALA on the modulation of insulin resistance in ER-stressed HepG2 cells, and we explored the potential mechanism of this effect. HepG2 cells were incubated with tunicamycin (Tun) for 6h to establish an ER stress cell model. Tun treatment induced ER stress, mitochondrial dysfunction and insulin resistance. Interestingly, ALA had no significant effect on ER stress signals. Pretreatment of the ER stress cell model with ALA for 24h improved insulin sensitivity, restored the expression levels of mitochondrial oxidative phosphorylation (OXPHOS) complexes and increased intracellular ATP production. Moreover, ALA augmented the β-oxidation capacity of the mitochondria. Importantly, ALA treatment could decrease oligomycin-induced mitochondrial dysfunction and then improved insulin resistance. Taken together, our data suggest that ALA prevents ER stress-induced insulin resistance by enhancing mitochondrial function.
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, Jilin, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Lei
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, Jilin, China.
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, Jilin, China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Gao
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, Jilin, China.
authors.forename: Xiliang
authors.initials: X
authors.lastname: Du
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, Jilin, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, Jilin, China.
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Peng
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, Jilin, China.
authors.forename: Shoupeng
authors.initials: S
authors.lastname: Fu
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, Jilin, China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, Jilin, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Zhe
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, Jilin, China. Electronic address: lixinwei100@126.com.
authors.forename: Xinwei
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, Jilin, China. Electronic address: liuguowen2008@163.com.
authors.forename: Guowen
authors.initials: G
authors.lastname: Liu
mesh_terms: D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D056945:Hep G2 Cells; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008954:Models, Biological; D009840:Oligomycins / Q000494:pharmacology; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D008063:Thioctic Acid / Q000494:pharmacology*; D014415:Tunicamycin / Q000494:pharmacology; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; D007328:Insulin; D009840:Oligomycins; C499638:PACS2 protein, human; D012333:RNA, Messenger; D033921:Vesicular Transport Proteins; D014415:Tunicamycin; D008063:Thioctic Acid; D048031:JNK Mitogen-Activated Protein Kinases
keywords: Alpha-lipoic acid (PubChem CID: 864); Endoplasmic reticulum stress; HepG2 cells; Insulin resistance; Mitochondrial dysfunction