Epigenetic patterns of two gene promoters (TNF-α and PON) in stroke considering obesity condition and dietary intake.

Some causal bases of stroke remain unclear, but the nutritional effects on the epigenetic regulation of different genes may be involved. The aim was to assess the impact of epigenetic processes of human tumor necrosis factor (TNF-α) and paraoxonase (PON) promoters in the susceptibility to stroke when considering body composition and dietary intake. Twenty-four patients (12 non-stroke/12 stroke) were matched by sex (12 male/12 female), age (mean 70 ± 12 years old), and BMI (12 normal-weight/12 obese; mean 28.1 ± 6.7 kg/m(2)). Blood cell DNA was isolated and DNA methylation levels of TNF-α (-186 to +349 bp) and PON (-231 to +250 bp) promoters were analyzed by the Sequenom EpiTYPER approach. Histone modifications (H3K9ac and H3K4me3) were analyzed also by chromatin immunoprecipitation in a region of TNF-α (-297 to -185). Total TNF-α promoter methylation was lower in stroke patients (p < 0.001) and showed no interaction with body composition (p = 0.807). TNF-α and PON total methylation levels correlated each other (r = 0.44; p = 0.031), especially in stroke patients (r = 0.72; p = 0.008). The +309 CpG methylation site from TNF-α promoter was related to body weight (p = 0.027) and the region containing three CpGs (from -170 to -162 bp) to the percentage of lipid intake and dietary indexes (p < 0.05) in non-stroke patients. The methylation of PON +15 and +241 CpGs was related to body weight (p = 0.021), waist circumference (p = 0.020), and energy intake (p = 0.018), whereas +214 was associated to the quality of the diet (p < 0.05) in non-stroke patients. When comparing stroke vs non-stroke patients regarding the histone modifications analyzed at TNF-α promoter, no changes were found, although a significant association was identified between circulating TNF-α level and H3K9ac with H3K4me3. TNF-α and PON promoter methylation levels could be involved in the susceptibility to stroke and obesity outcome, respectively. The dietary intake and body composition may influence this epigenetic regulation in non-stroke patients.

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

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.

Maternal weight gain induced by an obesogenic diet affects adipose accumulation, liver weight, and insulin homeostasis in the rat offspring depending on the sex.

BACKGROUND: The aim of this research was to analyze the influence of the maternal dietary intake before pregnancy, as well as the parental impact on the response to a transgenerational high-fat-diet in rats. METHODS: Ten female Wistar rats were fed a standard or a high-fat-sucrose (HFS) diet in the 8 weeks prior to pregnancy. Adult offsprings were assigned to a control or obesogenic diet for 8 weeks. Then, rat tissues and plasma samples were collected for analyzing tissue weight, liver triglycerides, and biochemical parameters such as triglycerides, HDL cholesterol, glucose, and insulin levels. RESULTS: The offspring of rats fed a HFS diet gained less weight when they were fed the same diet than those fed a HFS diet combined with maternal control diet. Insulin levels were higher in rats fed a HFS diet (p<0.05) in both sexes; however, maternal HFS diet reversed, partially in males and total- ly in females, this hormonal imbalance. In male newborns, diet-induced maternal weight gain before pregnancy significantly influenced visceral (R 2 =0.373) and subcutaneous (R 2 =0.239) adipose deposition as well as liver weight (R 2 =0.130). Paternal genetic make-up was also a relevant factor affecting adiposity in both sexes (R 2 =0.333 in visceral fat; R 2 =0.183 in subcutaneous fat in males, and 0.292 and 0.282, respectively in females) as well as plasma triglycerides (R 2 =0.193 in males and R 2 =0.251 in females). CONCLUSIONS: The genetic parental background and pre-natal maternal diet are important factors in the response to a hypercaloric diet and affect body composition and glucose homeostasis traits, including insulin secretion and homeostatic model assessment index.