Interrelationship between nuclear factor-erythroid-2-related factor 2, NADPH quinone oxidoreductase and lipoprotein-associated phospholipase A2 expression in young patients of metabolic syndrome
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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.
KeywordsMetabolic syndrome Lipoprotein-associated phospholipase A2 Nuclear factor E2-related factor 2 NAD(P)H quinone oxidoreductase 1
The authors covey their gratitude to the patients, and to the technical staff of the department of Biochemistry and hospital laboratory services.
Dr. Seema Garg and Dr. Mohit Mehndiratta conceptualised and designed the study. Pranav Malik and Dr. Seema Garg acquired the data with help from Dr. Rajarshi and Dr. Mohit Mehndiratta. Dr. Seema Garg statistically analysed and interpreted the data. Manuscript was drafted by Dr. Seema Garg, Dr. Rajarshi Kar and Dr. Mohit Mehndiratta. Critical review of manuscript was done by all authors.
The study was conducted under the Short Term Studentship program (reference ID: 2014—04698) of Indian Council of Medical Research, New Delhi.
Compliance with ethical standards
Conflict of interest.
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
Nuclear factor-erythroid-2-related factor 2 (Nrf2)
NAD(P)H quinone oxidoreductase-1
Lipoprotein-associated phospholipase A2
Methionine- and choline-deficient diet
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