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 - http://www.scopus.com/inward/record.url?scp=85082419577&partnerID=8YFLogxK
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 -