and Mitochondria Form a Mutually Regulating Circuit in the Prevention and Treatment of Metabolic Syndrome.

Metabolic syndrome (MetS) has become a major global public health problem and there is an urgent need to elucidate its pathogenesis and find more effective targets and modalities for intervention. Oxidative stress and inflammation are two of the major causes of MetS-related symptoms such as insulin resistance and obesity. is one of the important systems responding to oxidative stress and inflammation. As cells undergo stress, cysteines within are oxidized or electrophilically modified, allowing to escape ubiquitination and be translocated from the cytoplasm to the nucleus, facilitating the initiation of the antioxidant transcriptional program. Meanwhile, a growing body of evidence points out a specific modulation of mitochondrial homeostasis by . After nuclear translocation, activates downstream genes involved in various aspects of mitochondrial homeostasis, including mitochondrial biogenesis and dynamics, mitophagy, aerobic respiration, and energy metabolism. In turn, mitochondria reciprocally activate by releasing reactive oxygen species and regulating antioxidant enzymes. In this review, we first summarize the interactions between and mitochondria in the modulation of oxidative stress and inflammation to ameliorate MetS, then propose that and mitochondria form a mutually regulating circuit critical to maintaining homeostasis during MetS. Targeting the -mitochondrial circuit may be a promising strategy to ameliorate MetS, such as obesity, diabetes, and cardiovascular diseases.