Improvement of NRF2 gene expression and antioxidant status in patients with type 2 diabetes mellitus after supplementation with omega-3 polyunsaturated fatty acids: A double-blind randomised placebo-controlled clinical trial

Diabetes Res Clin Pract. 2020 Apr:162:108120. doi: 10.1016/j.diabres.2020.108120. Epub 2020 Mar 16.

Abstract

Background: Nrf2 is a transcription factor that induces the expression of several proteins with antioxidant properties such as sestrin2 (Sesn2) and is therefore considered as the major regulator of anti-oxidative defence system.

Objectives: The aim of this research was to study the effect of supplementation with n-3 PUFAs on the antioxidant status and the gene expression of Nrf2 and Sestrin2 (Sesn2) in patients with type 2 diabetes mellitus (T2DM).

Participants: Sixty patients with T2DM were enrolled in a placebo-controlled, double-blind, randomised clinical trial.

Intervention and design: The participants were randomly allocated to two intervention groups receiving either n-3 PUFAs (2,700 mg/day) (n = 30) or placebo soft gels containing 900 mg of edible paraffin (n = 30). The main outcome measures were the expression of Sesn2 and Nrf2 genes which were assessed in peripheral blood mononuclear cells (PBMCs) after RNA extraction and cDNA synthesis by real-time PCR. Total antioxidant status in plasma samples was also measured based on the ferric reducing ability of plasma.

Results: NRF2 gene expression was significantly increased in n-3 PUFA-supplemented subjects, compared with the placebo group. Plasma total antioxidant status was also significantly augmented in n-3 PUFA-supplemented subjects. SESN2 gene expression was not significantly affected by n-3 PUFA supplementation although a slight up-regulation was observed.

Conclusion: Supplementation with n-3 PUFAs enhanced NRF2 gene expression and improved overall antioxidant capacity and thus might be considered beneficial in the amelioration of oxidative stress and prevention of T2DM complications.

Trial registration: IRCT20150926024198N4.

Keywords: Antioxidants; Gene expression; NRF2; Omega-3 fatty acids; Sestrin 2; Type 2 diabetes.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Antioxidants / metabolism*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Double-Blind Method
  • Fatty Acids, Omega-3 / pharmacology
  • Fatty Acids, Omega-3 / therapeutic use*
  • Female
  • Gene Expression / genetics*
  • Humans
  • Male
  • Middle Aged
  • NF-E2-Related Factor 2 / metabolism*

Substances

  • Antioxidants
  • Fatty Acids, Omega-3
  • NF-E2-Related Factor 2