Obesity and NRF2-mediated cytoprotection: Where is the missing link?

Liliya V. Vasileva, Martina S. Savova, Kristiana M. Amirova, Albena Dinkova-Kostova, Milen I. Georgiev (Lead / Corresponding author)

    Research output: Contribution to journalReview articlepeer-review

    81 Citations (Scopus)
    284 Downloads (Pure)

    Abstract

    The expanding dimensions of the global health crisis of overweight population has defined the term “globesity”. Among the most common pathological conditions connected with excessive adiposity are hyperglycemia, insulin resistance, dyslipidemia and hypertension which result in chronic non-communicable diseases (NCD) such as metabolic syndrome (MetS), type 2 diabetes (T2D), and nonalchoholic steatohepatitis (NASH). The contribution of inflammatory-immune reactions in obesity and its related co-morbidities is unequivocal. Increased levels of free fatty acids (FFA), reactive oxygen species (ROS) and reactive nitrogen species (RNS) overloads the homeostatic system resulting in pro-inflammatory adipokines secretion, immune-activation and chronic inflammation in obesity. The cellular mechanisms of defense against oxidative stress are orchestrated by the transcription factor nuclear factor erythroid 2 p45-related factor 2 (NRF2). Excessive oxidative stress in the cell activates NRF2 which upregulates genes encoding major cytoprotective enzymes such as NAD(P)H:quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HO1), and glutathione Stransferases (GST). The present review aims to clarify the interconnections between chronic inflammation, oxidative overload and NRF2-mediated cytoprotection as potential therapeutic approach in obesity.
    Original languageEnglish
    Article number104760
    Number of pages9
    JournalPharmacological Research
    Volume156
    Early online date20 Mar 2020
    DOIs
    Publication statusPublished - Jun 2020

    Keywords

    • Chronic inflammation
    • KEAP1
    • Medicinal plants
    • NRF2
    • Obesity
    • Pharmacotherapy

    ASJC Scopus subject areas

    • Pharmacology

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