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The pivotal role of Nrf2 activators in adipocyte biology

期刊

PHARMACOLOGICAL RESEARCH
卷 173, 期 -, 页码 -

出版社

ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.phrs.2021.105853

关键词

Adipogenesis; Oxidative stress; Nrf2 signaling pathway; Nrf2 activators

资金

  1. Indian Council of Medical Research (ICMR), Government of India [MP 2020-4084]

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Adipose tissue plays a crucial role in maintaining metabolic homeostasis, but overnutrition can lead to abnormal increase in adipocytes, causing obesity and other chronic complications. Oxidative stress is closely involved in the pathogenesis of obesity, and the Nrf2 signaling pathway plays a significant role in regulating oxidative and inflammatory responses. Researchers are currently seeking novel compounds to modulate Nrf2 activity for the management of adipogenesis and obesity.
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 alpha, (C/EBP-alpha), C/EBP-beta and peroxisome proliferator-activated receptor gamma (PPAR gamma) 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.

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