Interrelationship between nuclear factor-erythroid-2-related factor 2, NADPH quinone oxidoreductase and lipoprotein-associated phospholipase A2 expression in young patients of metabolic syndrome

Abstract

Metabolic syndrome (MS) is associated with inflammation and oxidative stress (OS). Keap1/Nrf2/ARE is a cytoprotective pathway induced by OS and inflammation. This study aims to evaluate the expression of nuclear factor-erythroid-2-related factor 2 (Nrf2) and its downstream target gene NADPH quinone oxidoreductase-1 (NQO-1) in MS. Since lipoprotein-associated phospholipase A2(LpPLA2) is an important inflammatory marker believed to have a role in complications of MS, the association of its expression with that of Nrf2 and NQO-1 was also studied. Medical students (n = 26) were categorised in two groups according to NCEP ATP III criteria with WHO criteria for obesity for South Asian region: patients of MS (n = 13) and controls (n = 13). mRNA expression of Nrf2, NQO-1 and LpPLA2 genes was evaluated by qPCR in blood using specific primers. Fold change was calculated by 2–ΔΔcT method keeping β-actin as internal control. Expression of NQO-1 and LpPLA2 was found to be higher in MS. However, Nrf2 expression was low in patients who had hypertriglyceridemia when compared with patients with normal triglyceride levels. A significant correlation was observed in expression of LpPLA2, with Nrf2 and NQO-1. Our data suggests that there may be compensatory activation of antioxidant defence mechanism in young patients of MS. Further evidence is provided by higher expression of LpPLA2 and its correlation with Nrf2 and NQO-1 in MS which suggests that inflammatory stress may induce expression of genes of cytoprotective pathways. Additionally, this study, for the first time, indicates that Nrf2 may have some role in regulating triglyceride (TG) concentration.