Abstract
BackgroundExcess weight is a strong risk factor for the development of dysglycaemia. It has been suggested that changes in the metabolism microRNAs, small non-coding RNAs that regulate gene expression, could precede late glycaemic changes. Vitamin E in turn may exert important functions in methylation and gene expression processes. This study aimed to determine the effect of α-tocopherol on glycaemic variables and miR-9-1 and miR-9-3 promoter DNA methylation in overweight women.MethodsA randomized, double-blind, exploratory, placebo-controlled study was conducted in overweight and obese adult women (n = 44) who ingested synthetic vitamin E (all-rac-α-tocopherol), natural source vitamin E (RRR-rac-α-tocopherol) or placebo capsules and were followed up for a period of 8 weeks. Supplemented groups also received dietary guidance for an energy-restricted diet. An additional group that received no supplementation and did not follow an energy-restricted diet was also followed up. The intervention effect was evaluated by DNA methylation levels (quantitative real-time PCR assay) and anthropometric and biochemical variables (fasting plasma glucose, haemoglobin A1C, insulin, and vitamin E).ResultsIncreased methylation levels of the miR-9-3 promoter region (P < 0.001) and reduced haemoglobin A1C (P < 0.05) were observed in the natural source vitamin E group after intervention. Increased fasting plasma glucose was observed in the synthetic vitamin E group, despite the significant reduction of anthropometric variables compared to the other groups.Conclusionsα-Tocopherol from natural sources increased methylation levels of the miR-9-3 promoter region and reduced haemoglobin A1C in overweight women following an energy-restricted diet. These results provide novel information about the influence of vitamin E on DNA methylation.Trial registrationClinicalTrials.gov, NCT02922491. Registered 4 October, 2016.
Highlights
Excess weight is a strong risk factor for the development of dysglycaemia
Increased fasting plasma glucose was observed in the synthetic vitamin E group, despite the significant reduction of anthropometric variables compared to the other groups
Results at baseline Before the intervention period, the groups supplemented with synthetic vitamin E, natural vitamin E (RRR-α-tocopherol) or placebo and the non-intervention group were homogenous with regard to miR-9-1 and miR-9-3 methylation levels, anthropometric variables, family income, physical activity practice, menopausal status (Table 1), glycaemic control variables and serum vitamin E (Table 2)
Summary
It has been suggested that changes in the metabolism microRNAs, small non-coding RNAs that regulate gene expression, could precede late glycaemic changes. Obesity is a pro-inflammatory state with a broad impact on health and is the main risk factor for metabolic diseases such as diabetes, with an alarming increase worldwide [1]. Epigenetic mechanisms such as DNA methylation and regulation by microRNAs (miRs) play a central role in the obesogenic environment [2, 3]. Conditions associated with obesity, such as chronic inflammation, hyperglycaemia and hyperlipidaemia, are related to changes in DNA methylation status and gene expression [2, 4]. The miRs perform functions of mRNA repression or degradation, leading to the impediment of translation and acting as post-transcriptional regulators [9,10,11]
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