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

TY - JOUR

T1 - Obesity and NRF2-mediated cytoprotection

T2 - Where is the missing link?

AU - Vasileva, Liliya V.

AU - Savova, Martina S.

AU - Amirova, Kristiana M.

AU - Dinkova-Kostova, Albena

AU - Georgiev, Milen I.

N1 - Copyright © 2020. Published by Elsevier Ltd.

PY - 2020/6

Y1 - 2020/6

N2 - 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.

AB - 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.

KW - Chronic inflammation

KW - KEAP1

KW - Medicinal plants

KW - NRF2

KW - Obesity

KW - Pharmacotherapy

UR - https://www.scopus.com/pages/publications/85082419577

U2 - 10.1016/j.phrs.2020.104760

DO - 10.1016/j.phrs.2020.104760

M3 - Review article

C2 - 32205234

SN - 1043-6618

VL - 156

JO - Pharmacological Research

JF - Pharmacological Research

M1 - 104760

ER -