Abstract
During chronic cold stress, thermogenic adipocytes generate heat through uncoupling of mitochondrial respiration from ATP synthesis. Recent discovery of various dietary phytochemicals, endogenous metabolites, synthetic compounds, and their molecular targets for stimulating thermogenesis has provided promising strategies to treat or prevent obesity and its associated metabolic diseases. Nuclear factor E2 p45-related factor 2 (Nrf2) is a stress response protein that plays an important role in obesity and metabolisms. However, both Nrf2 activation and Nrf2 inhibition can suppress obesity and metabolic diseases. Here, we summarized and discussed conflicting findings of Nrf2 activities accounting for part of the variance in thermogenesis and energy metabolism. We also discussed the utility of Nrf2-activating mechanisms for their potential applications in stimulating energy expenditure to prevent obesity and improve metabolic deficits.
Highlights
Nuclear factor E2 p45-related factor 2 (Nrf2) KO C57BL6;129SV C57BL6Diet (Start/Duration) HFD (3–4 w/12 w) (9–10 w/180 d) Body Mass IR Oxidative Inflammation
We reviewed recent findings regarding the Nrf2 activity on thermogenesis and energy metabolism and further discussed its activation for potential applications in preventing obesity and metabolic diseases
Tocopherols, and phytochemicals in cells can disrupt the interaction between Kelch-like ECH-associated protein 1 (Keap1) and Nrf2 to drive antioxidant response element (ARE)-mediated cytoprotective gene transcription
Summary
In response to external stimuli, physiological signals are required to activate thermogenic effectors, leading to increased thermogenic respiration. Thiol redox state of BAT is shifting toward more pro-oxidant conditions during cold exposure by generating mitochondrial ROS [9,10,11] Under these oxidative stress conditions, Nrf, a master regulator of anti-oxidant response, is activated to remove excess ROS [12,13]. Nrf activation or suppression exhibits conflicting results in published literature concerning its effects against obesity and metabolic dysregulations. To resolve this discrepancy, we reviewed recent findings regarding the Nrf activity on thermogenesis and energy metabolism and further discussed its activation for potential applications in preventing obesity and metabolic diseases.
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