Dietary supplementation with methyl donors reduces fatty liver and modifies the fatty acid synthase DNA methylation profile in rats fed an obesogenic diet

Abstract

Non-alcoholic fatty liver disease (NAFLD) is one of the first hepatic manifestations of metabolic syndrome, whose progression can lead to cirrhosis and hepatic carcinoma. Interestingly, methyl donor supplementation could improve obesogenic diet-induced hepatic triglyceride accumulation. The aim of this research is to describe methyl donor effects on a high-fat-sucrose (HFS) diet in both sexes and epigenetic changes induced on fatty acid synthase (FASN) promoter methylation pattern as well as gene expression of NAFLD key metabolic genes. Twenty-four male and 28 female Wistar rats were assigned to three dietary groups: control, HFS, and HFS supplemented with methyl donors (choline, betaine, vitamin B12, and folic acid). After 8 weeks of treatment, somatic, biochemical, mRNA, and epigenetic measurements were performed. Rats fed the HFS diet presented an overweight phenotype and alterations in plasma biochemical measurements. Methyl donor supplementation reverted the HFS-diet-induced hepatic triglyceride accumulation. Analysis of FASN promoter cytosine methylation showed changes in both sexes due to the obesogenic diet at -1,096, -780, -778, and -774 CpG sites with respect to the transcriptional start site. Methyl donor supplementation modified DNA methylation at -852, -833, -829, -743, and -733 CpGs depending on the sex. RT-PCR analysis confirmed that FASN expression tended to be altered in males. Our findings reinforce the hypothesis that methyl donor supplementation can prevent hepatic triglyceride accumulation induced by obesogenic diets in both sexes. Changes in liver gene expression profile and epigenetic-mediated mechanisms related to FASN DNA hypermethylation could be involved in methyl donor-induced NAFLD improvement.

Methyl donor supplementation in rats reverses the deleterious effect of maternal separation on depression-like behaviour

“…Moreover, IR expression in the hippocampus was decreased by MS and reversed by MD. In this sense, studies in rodents have previously focused on the protective effects of dietary supplementation with methyl donors on obesity [49] and hepatic fat accumulation [29,55], suggesting an improvement of diet-induced insulin resistance by activating IR and the downstream signalling pathways.…”

“…Based on this information and on previously reported beneficial effects of the methyl donor supplementation (MD) on hepatic triglyceride accumulation induced by an obesogenic diet [29], we hypothesized that a diet rich in methyl donors during adulthood could diminish the effect of adverse early life conditions in rats. The novelty of the current work lies in studying some of the epigenetic mechanisms that can be modulated by the diet (in this case, methyl donor supplementation) in order to counteract early life stress-induced depression-like behaviour.…”

Cigarette smoking induces small airway epithelial epigenetic changes with corresponding modulation of gene expression

“…Cynomolgus monkeys transitioned from a high soy diet to a low soy diet had change in global DNA methylation levels in liver and muscle tissue (12). Adult rats fed high-fat sucrose diets supplemented with methyl donors had modified liver DNA methylation levels of specific CpGs on the fatty acid synthase (FASN) gene in a diet-dependent manner (13).…”

Tasks of some dietary essential nutrients on epigenetics and one carbon metabolism in livestock during production

“…A double-blind clinical study of folate supplementation raised plasma betaine levels in a dose-dependent style following folate supplement [44]. Plasma choline levels existed reactive to reduction and subsequent repletion of folate intake [45]. Betaine and choline have additional biological galas not shared by each other.…”