title: The effects of choline on hepatic lipid metabolism, mitochondrial function and antioxidative status in human hepatic C3A cells exposed to excessive energy substrates.
abstract: Choline plays a lipotropic role in lipid metabolism as an essential nutrient. In this study, we investigated the effects of choline (5, 35 and 70 μM) on DNA methylation modifications, mRNA expression of the critical genes and their enzyme activities involved in hepatic lipid metabolism, mitochondrial membrane potential (Δψm) and glutathione peroxidase (GSH-Px) in C3A cells exposed to excessive energy substrates (lactate, 10 mM; octanoate, 2 mM and pyruvate, 1 mM; lactate, octanoate and pyruvate-supplemented medium (LOP)). Thirty five micromole or 70 μM choline alone, instead of a low dose (5 μM), reduced hepatocellular triglyceride (TG) accumulation, protected Δψm from decrement and increased GSH-Px activity in C3A cells. The increment of TG accumulation, reactive oxygen species (ROS) production and Δψm disruption were observed under LOP treatment in C3A cells after 72 h of culture, which were counteracted by concomitant treatment of choline (35 μM or 70 μM) partially via reversing the methylation status of the peroxisomal proliferator-activated receptor alpha (PPARα) gene promoter, upregulating PPARα, carnitine palmitoyl transferase-I (CPT-I) and downregulating fatty acid synthase (FAS) gene expression, as well as decreasing FAS activity and increasing CPT-I and GSH-Px activities. These findings provided a novel insight into the lipotropic role of choline as a vital methyl-donor in the intervention of chronic metabolic diseases.
authors.affiliation: Department of Clinical Nutrition, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China. jacky284868@163.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430060, China. wywytwin@163.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Clinical Nutrition, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China. tangqingya@163.com.
authors.forename: Qingya
authors.initials: Q
authors.lastname: Tang
authors.affiliation: Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430060, China. lengyan890801@sina.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Leng
authors.affiliation: Department of Clinical Nutrition, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China. caiw1978@126.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Cai
mesh_terms: D000975:Antioxidants / Q000008:administration & dosage*; D002210:Caprylates / Q000378:metabolism; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002794:Choline / Q000008:administration & dosage*; D019175:DNA Methylation / Q000187:drug effects; D015536:Down-Regulation; D064429:Fatty Acid Synthases / Q000235:genetics / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects*; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D019289:Pyruvic Acid / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014280:Triglycerides; D015854:Up-Regulation
chemical_list: D000975:Antioxidants; D002210:Caprylates; D047493:PPAR alpha; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D014280:Triglycerides; D019344:Lactic Acid; D019289:Pyruvic Acid; D005979:Glutathione Peroxidase; D002334:Carnitine O-Palmitoyltransferase; D064429:Fatty Acid Synthases; D002794:Choline; C031492:octanoic acid