Impact of Nrf2 Signaling Pathway in Adipogenesis and Its Role in Insulin Resistance Associated with Obesity

Abstract

A chronic positive energy balance, as observed in obesity, leads to an increase in circulating free fatty acids (FFAs), which can activate inflammatory signaling in M1 macrophages. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that controls the expression of several genes involved in the cellular response to redox changes, xenobiotic detoxification, and adipogenesis. The signaling pathway that leads to the migration of Nrf2 to the cell nucleus is well known, but its role in regulating the adipogenesis process remains controversial. Activation of the Nrf2 signaling pathway leads to increased expression of critical enzymes involved in FFA esterification, such as triglycerides, the safest way to store FFAs. This paper reviews recent information on the role of Nrf2 in the differentiation of preadipocytes into adipocytes, which helps explain controversial information. Adipocytes specialize in storing FFAs as triglycerides and act as endocrine cells. However, in obesity, its functions are dysregulated along with the macrophage-induced inflammation of adipose tissue. Adipose tissue inflammation is the main cause of low-grade systemic inflammation observed in obese patients and the main link between adipose tissue inflammation and obesity-associated insulin resistance. Therefore, a deeper understanding of the role of Nrf2 in the process of adipogenesis is essential for the development of new agonists to prevent metabolic abnormalities associated with obesity.