title: Acetyl-CoA carboxylase 2 suppression rescues human proximal tubular cells from palmitic acid induced lipotoxicity via autophagy.
abstract: Autophagy is a catabolic process that degrades damaged proteins and organelles in mammalian cells. Although acetyl-CoA carboxylase 2 (ACC2) plays a crucial role in the fatty acid metabolism, it keeps unknown whether ACC2 is associated with autophagic activity. The present work was designed to investigate the effects of ACC2 on palmitic acid (PA) induced lipotoxicity in human proximal tubular cells and the putative role of autophagy in this process. Here we show that autophagy was induced by PA in HK-2 cells. Moreover, the PA induced autophagy was regulated both by ACC2 suppression and CPTI inhibitor treatment, which represent an altered fatty acid β-oxidation. And the knockdown of ACC2 reduced PA-induced autophagy and thus protects the cells from PA-induced lipotoxicity with attenuated lipid accumulation and rescued cell viability. Collectively, the present study proposed a novel autophagy-involved mechanism of PA-induced renal lipotoxicity and provided potential therapeutic strategy by modulating lipid β-oxidation for diabetic nephropathy.
authors.affiliation: Department of Central Laboratory, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xin
authors.affiliation: School of Medicine, Shandong University, Jinan, 250012, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhao
authors.affiliation: School of Medicine, Shandong University, Jinan, 250012, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Nephrology, Qianfoshan Hospital Affiliated to Shandong University, Jinan, 250014, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.affiliation: School of Medicine, Shandong University, Jinan, 250012, China.
authors.forename: Zhaoping
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Nutrition, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China.
authors.forename: Liyong
authors.initials: L
authors.lastname: Chen
authors.affiliation: School of Medicine, Shandong University, Jinan, 250012, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Shandong University School of Medicine, Jinan, 250012, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yi
authors.affiliation: Department of Nephrology, Qianfoshan Hospital Affiliated to Shandong University, Jinan, 250014, China. Electronic address: wanyanshaoqiang@163.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wan
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000235:genetics / Q000378:metabolism*; D001343:Autophagy; D002460:Cell Line; D002470:Cell Survival; D003928:Diabetic Nephropathies / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020868:Gene Silencing; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000166:cytology* / Q000378:metabolism / Q000473:pathology*; D010084:Oxidation-Reduction; D019308:Palmitic Acid / Q000378:metabolism*
chemical_list: D019308:Palmitic Acid; C520105:ACACB protein, human; D000103:Acetyl-CoA Carboxylase
keywords: ACC2; Autophagy; Diabetic nephropathy; Fatty acid β-oxidation; Lipotoxicity