The pivotal role of Nrf2 activators in adipocyte biology. (November 2021)

• Record Type: Journal Article
• Authors: Annie-Mathew, A.S.; Prem-Santhosh, Subramanian; Jayasuriya, Ravichandran; Ganesh, Goutham; Ramkumar, Kunka Mohanram; Sarada, D.V.L.
• Is Part Of: Pharmacological research. Volume 173(2021)
• Publication Date: 2021-11
• Subjects: ATGL Adipocyte Triglyceride Lipase -- CAT Catalase -- HDL High-Density Lipoprotein -- IFN Interferon -- IL Interleukin -- JNK c-Jun N-terminal kinase -- KLF Kruppel-Like Factor -- LDL Low-Density Lipoprotein -- LPL Lipoprotein Lipase -- MMP3 Matrix Metalloproteinase 3 -- MnSOD Manganese Superoxide Dismutase -- NF-κB nuclear factor kappa-light-chain-enhancer of activated B cells -- NRF1 Nuclear Respiratory Factor 1 -- PGC-1α PPARγ Coactivator-1α -- SREBP-1c Sterol Regulatory Element-Binding Protein-1c -- TFAM Transcription Factor A - Mitochondrial -- TNF-α Tumor Necrosis Factor-α -- UCP1 Uncoupling Protein 1; Adipogenesis -- Oxidative stress -- Nrf2 signaling pathway -- Nrf2 activators; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2021.105853
• Languages: English
• ISSNs: 1043-6618

Abstract

Abstract: Adipose tissue is instrumental in maintaining metabolic homeostasis by regulating energy storage in the form of triglycerides. In the case of over-nutrition, adipocytes favorably regulate lipogenesis over lipolysis and accumulate excess triglycerides, resulting in increased adipose tissue mass. An abnormal increase in hypertrophic adipocytes is associated with chronic complications such as insulin resistance, obesity, diabetes, atherosclerosis and nonalcoholic fatty liver disease. Experimental studies indicate the occurrence of oxidative stress in the pathogenesis of obesity. A common underlying link between increasing adipose tissue mass and oxidative stress is the Nuclear Factor Erythroid 2-related factor 2 (Nrf2), Keap1-Nrf2-ARE signaling, which plays an indispensable role in metabolic homeostasis by regulating oxidative and inflammatory responses. Additionally, Nrf2 also activates CCAAT/enhancer-binding protein α, (C/EBP-α), C/EBP-β and peroxisome proliferator-activated receptor γ (PPARγ) the crucial pro-adipogenic factors that promote de novo adipogenesis. Hence, at the forefront of research is the quest for prospecting novel compounds to modulate Nrf2 activity in the context of adipogenesis and obesity. This review summarizes the molecular mechanism behind the activation of the Keap1-Nrf2-ARE signaling network and the role of Nrf2 activators in adipocyte pathophysiology. Graphical Abstract: ga1