Nrf2 coordinates redox-metabolic homeostasis required for lipid deposition in rat visceral adipose tissue during the re-acclimation of rats after cold

Abstract

Тight control of the lipid-deposition function of white adipose tissue (WAT) defines the overall metabolic homeostasis and entails coordinated antioxidant response. We aimed to reveal temporal changes in the antioxidant defence (AD) that is a prerequisite for lipid metabolism in the visceral WAT over 45 days of re-acclimation to room temperature (RT, 22±1 °C) in rats pre-acclimated to cold (45 days, 4±1 °C). The Nuclear factor erythroid 2–related factor 2 (Nrf2) and its downstream antioxidant targets, as well as key lipogenic enzymes were examined in epididymal WAT (eWAT) and compared to the RT-maintained control. Upregulation of Nrf2 protein expression observed from the 1-12th day of re-acclimation was followed by an increase in the glutathione level (3-7th day) and the protein expression of copper, zinc superoxide dismutase (3-12th day), manganese superoxide dismutase (1-12th day), thioredoxin (1-45th day), and glutathione peroxidase (1-45th day). Such time-dependent changes in AD during re-acclimation coincided with increases in the lipogenic enzymes acetyl-CoA carboxylase and fatty acid synthase that were further supported by elevated glyceraldehyde 3-phosphate dehydrogenase and glucose 6-phosphate dehydrogenase protein levels. Observed redox-metabolic integration in eWAT resulted in the restitution of relative eWAT mass on the 12th day of re-acclimation. It can be concluded that Nrf2-coordinated redox-metabolic changes drive the restitution of eWAT lipid depot during the re-acclimation of rats after cold. These results show a novel role of Nrf2 in regulating redox-metabolic signaling under homeostatic conditions and its relevance in visceral adiposity in different metabolic diseases.