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 Publisher Pubmed



Golpour P¹ ; Nourbakhsh M^{2, 3} ; Mazaherioun M⁴ ; Janani L⁵ ; Nourbakhsh M^{2, 3} ; Yaghmaei P¹
Source: Diabetes Research and Clinical Practice Published:2020

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. © 2020 Elsevier B.V.