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.
Highlights
IntroductionCholine is an essential nutrient for human health, which exerts various physiological functions:(1) it is acetylated to generate acetylcholine, the important neurotransmitter; (2) it is oxidized to pass methyl to S-adenosylmethionine, a universal methyl group donor, which participates in the methylation-dependent biosynthesis of DNA, RNA and protein; (3) it is phosphorylated to synthesize phosphatidylcholine, a major constituent of cell and mitochondrial membranes, which is involved in the mitochondrial bioenergetics regulating lipid and glucose metabolism [1,2,3] and participates in the packaging and exporting of triglyceride (TG) in very low density lipoprotein (VLDL), as well as the solubilizing of bile salts for secretion [2,3,4].Choline deficiency (CD) contributes to various disorders in animals and humans, with liver as its main target [5]
Humans deprived of choline have been observed to develop fatty liver, liver cell death or skeletal muscle damage [2,6,7], which were further evidenced by another clinical study showing that patients fed with total parenteral nutrition (TPN) solutions low in choline resulted in TPN-associated liver disease [2,8]
Low choline results in the altered composition of mitochondrial membranes, reduced mitochondrial membrane potential (Δψm) [2,11], decreased ATP production [2,12] and perturbation in fatty acid β-oxidation in rats fed a choline-deficient diet [2,13]. This mitochondrial dysfunction has been identified in the process of the increment of reactive oxygen species (ROS), the loss of Δψm, cellular apoptosis and hepatocarcinogenesis induced by choline deficiency in SV40-immortalized rat hepatocytes (CWSV-1) [14,15]
Summary
Choline is an essential nutrient for human health, which exerts various physiological functions:(1) it is acetylated to generate acetylcholine, the important neurotransmitter; (2) it is oxidized to pass methyl to S-adenosylmethionine, a universal methyl group donor, which participates in the methylation-dependent biosynthesis of DNA, RNA and protein; (3) it is phosphorylated to synthesize phosphatidylcholine, a major constituent of cell and mitochondrial membranes, which is involved in the mitochondrial bioenergetics regulating lipid and glucose metabolism [1,2,3] and participates in the packaging and exporting of triglyceride (TG) in very low density lipoprotein (VLDL), as well as the solubilizing of bile salts for secretion [2,3,4].Choline deficiency (CD) contributes to various disorders in animals and humans, with liver as its main target [5]. Low choline results in the altered composition of mitochondrial membranes, reduced mitochondrial membrane potential (Δψm) [2,11], decreased ATP production [2,12] and perturbation in fatty acid β-oxidation in rats fed a choline-deficient diet [2,13]. This mitochondrial dysfunction has been identified in the process of the increment of reactive oxygen species (ROS), the loss of Δψm, cellular apoptosis and hepatocarcinogenesis induced by choline deficiency in SV40-immortalized rat hepatocytes (CWSV-1) [14,15]. The specific mechanisms linking choline, DNA methylation and metabolic diseases, such as non-alcoholic fatty liver disease (NAFLD), remain to be clearly defined
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
