The Nrf2 in Obesity: A Friend or Foe?

Obesity and its complications have become serious global health concerns recently and increasing work has been carried out to explicate the underlying mechanism of the disease development. The recognized correlations suggest oxidative stress and inflammation in expanding adipose tissue with excessive fat accumulation play important roles in the pathogenesis of obesity, as well as its associated metabolic syndromes. In adipose tissue, obesity-mediated insulin resistance strongly correlates with increased oxidative stress and inflammation. Nuclear factor erythroid 2-related factor 2 (Nrf2) has been described as a key modulator of antioxidant signaling, which regulates the transcription of various genes coding antioxidant enzymes and cytoprotective proteins. Furthermore, an increasing number of studies have demonstrated that Nrf2 is a pivotal target of obesity and its related metabolic disorders. However, its effects are controversial and even contradictory. This review aims to clarify the complicated interplay among Nrf2, oxidative stress, lipid metabolism, insulin signaling and chronic inflammation in obesity. Elucidating the implications of Nrf2 modulation on obesity would provide novel insights for potential therapeutic approaches in obesity and its comorbidities.