α-Tocopherol influences glycaemic control and miR-9-3 DNA methylation in overweight and obese women under an energy-restricted diet: a randomized, double-blind, exploratory, controlled clinical trial

Rafaella Cristhine Pordeus Luna; Mayara Karla Dos Santos Nunes; Mussara Gomes Cavalcante Alves Monteiro; Cássia Surama Oliveira da Silva; Rayner Anderson Ferreira do Nascimento; Raquel Patrícia Ataíde Lima; Flávia Cristina Fernandes Pimenta; Naila Francis Paulo de Oliveira; Darlene Camati Persuhn; Aléssio Tony Cavalcanti de Almeida; Alcides da Silva Diniz; Cristina Wide Pissetti; Rodrigo Pinheiro Toledo Vianna; Flavia Emília Leite de Lima Ferreira; Maria da Conceição Rodrigues Gonçalves; Maria José de Carvalho Costa

doi:10.1186/s12986-018-0286-7

α-Tocopherol influences glycaemic control and miR-9-3 DNA methylation in overweight and obese women under an energy-restricted diet: a randomized, double-blind, exploratory, controlled clinical trial

Nutr Metab (Lond). 2018 Jul 11:15:49. doi: 10.1186/s12986-018-0286-7. eCollection 2018.

Authors

Rafaella Cristhine Pordeus Luna^{1

2}, Mayara Karla Dos Santos Nunes³, Mussara Gomes Cavalcante Alves Monteiro¹, Cássia Surama Oliveira da Silva⁴, Rayner Anderson Ferreira do Nascimento³, Raquel Patrícia Ataíde Lima¹, Flávia Cristina Fernandes Pimenta⁵, Naila Francis Paulo de Oliveira⁶, Darlene Camati Persuhn^{1

3

6}, Aléssio Tony Cavalcanti de Almeida⁷, Alcides da Silva Diniz⁸, Cristina Wide Pissetti⁹, Rodrigo Pinheiro Toledo Vianna¹⁰, Flavia Emília Leite de Lima Ferreira¹⁰, Maria da Conceição Rodrigues Gonçalves^{1

10}, Maria José de Carvalho Costa^{1

10}

Affiliations

¹ 1Postgraduate in Nutrition Sciences, Health Sciences Center, Federal University of Paraíba (Universidade Federal da Paraíba), João Pessoa, Paraíba 58051-900 Brazil.
² 10Postgraduate in Nutrition Sciences, Health Sciences Center, Health and Nutrition Studies Interdisciplinary Center (NIESN), Federal University of Paraíba (Universidade Federal da Paraíba), Castelo Branco, João Pessoa, Paraíba 58051-900 Brazil.
³ 2Postgraduate Program in Cellular and Molecular Biology, Federal University of Paraíba (Universidade Federal da Paraíba), João Pessoa, Paraíba 58059-900 Brazil.
⁴ 3Health and Nutrition Studies Interdisciplinary Center, Health Sciences Center, Federal University of Paraíba (Universidade Federal da Paraíba), João Pessoa, Paraíba 58051-900 Brazil.
⁵ 4Department of Internal Medicine, Health Sciences Center, Federal University of Paraíba (Universidade Federal da Paraíba), João Pessoa, Paraíba 58051-900 Brazil.
⁶ 5Departament of Molecular Biology, Federal University of Paraíba (Universidade Federal da Paraíba), João Pessoa, 58059-900 Paraíba Brasil.
⁷ 6Department of Economics, Postgraduate Program in Applied Economics and Economics of the Public Sector, Center for Applied Social Sciences, Federal University of Paraíba (Universidade Federal da Paraíba), João Pessoa, Paraíba 58059-900 Brazil.
⁸ 7Department of Nutrition, Graduate Program in Nutrition, Health Sciences Center, Federal University of Pernambuco, Recife, Pernambuco 50670901 Brazil.
⁹ 8Department of Obstetrics and Gynecology, Health Sciences Center, Federal University of Paraíba (Universidade Federal da Paraíba), João Pessoa, Paraíba 58051-900 Brazil.
¹⁰ 9Department of Nutrition, Graduate Program in Nutrition Sciences, Health Sciences Center, Federal University of Paraíba (Universidade Federal da Paraíba), João Pessoa, Paraíba 58051-900 Brazil.

Abstract

Background: Excess 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.

Methods: A 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).

Results: Increased 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.

Conclusions: α-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 registration: ClinicalTrials.gov, NCT02922491. Registered 4 October, 2016.

Keywords: DNA methylation; Diet; Fasting plasma glucose; Haemoglobin A1C; Obesity; miR-9; miR-9-1; miR-9-3; α-Tocopherol.

Associated data

ClinicalTrials.gov/NCT02922491