Nrf3-deficient mice are not protected against acute lung and adipose tissue damages induced by butylated hydroxytoluene

Abstract 

We found that both wild type and Nrf3 (NF-E2-related factor 3) deficient mice are sensitive to BHT single administration exhibiting respiratory distress and considerably lose body weight following treatment. At time of sacrifice, the BHT-treated Nrf3^−/− mice had lost significantly more body weight than their WT counterparts. In the lung, transcript levels of the transcription factors Nrf1, Nrf2 and Nrf3 were differentially regulated by BHT treatment. In addition, genes implicated in adipogenesis were repressed following BHT exposure in the white adipose tissue. Together, our data provide the first evidence that BHT exposure not only affects lung function but also leads to impaired adipogenesis in adipocytes.

Abbreviations: ARE, antioxidant response element, BHT, butylated hydroxytoluene, Cebpb, CCAAT enhancer binding protein beta, CNC, cap ‘n’ collar, Fas, fatty acid synthase, Foxf1, forkhead box f1, Gclc, catalytic subunit of glutamate cysteine ligase, Gclm, modifier subunit of glutamate cysteine ligase, Hmox1, heme oxygenase 1, Maf, musculoaponeurotic fibrosarcoma, MARE, Maf recognition element, Nrf, NF-E2-related factor, Pparg, peroxisome proliferator-activated receptor gamma, Ptgs, prostaglandin-endoperoxide synthase, Srebp1, sterol regulatory element binding protein 1, WAT, white adipose tissue, WT, wild type

Keywords: Nrf3, Pparg, BHT, Acute lung injury, Adipogenesis