The Ahr and Nrf2 in White Adipose Tissue

Background: There is interaction between the AhR and the Nrf2. The latter decreases as a consequence of aging as well as other factors including insulin resistance/IGF resistance from oxidative stress as a result of ROS which may occur from toxicant exposure. Recent information provides evidence that Nrf2 plays a homeostatic function in adipose tissue and obesity. The AhR has been demonstrated to play a role in fatty liver disease. The Nrf2 plays a role in the expression of the AhR and its downstream targets and inhibits adipogenesis through AhR signaling. Shin explains that "tighter coupling between the AhR and the Nrf2 may result in the attuation of health risks by xenobiotics." He further explains that Nrf2 upregulated cytoprotective enzymes and CYPs through AhR.


Yoshinari writes, "The liver is the main organ of drug metabolism, but the expression and induction by xenobiotics of drug-metabolizing enzymes is also often observed in extrahepatic tissues......both AhR and Nrf2 pathways are active in WAT and that lipophilic compounds accumulated in WAT can activate these transcription factors to increase detoxification capability in the tissue.


Yoshinari, K., Okino, N., Sato, T., Sugatani, J., and Miwa, M. (2006). Induction of detoxifying enzymes in rodent white adipose tissue by aryl hydrocarbon receptor agonists and antioxidants. Drug Metab Dispos, 34(7):1081-1089. http://www.citeulike.org/group/7376/article/783432
Beyer, T. A., Xu, W., Teupser, D., auf dem Keller, U., Bugnon, P., Hildt, E., Thiery, J., Kan, Y. W. W., and Werner, S. (2008). Impaired liver regeneration in nrf2 knockout mice: role of ros-mediated insulin/igf-1 resistance. The EMBO journal, 27(1):212-223. http://www.citeulike.org/user/HEIRS/article/2067919
Shin, S., Wakabayashi, N., Misra, V., Biswal, S., Lee, G. H., Agoston, E. S., Yamamoto, M., and Kensler, T. W. (2007). Nrf2 modulates aryl hydrocarbon receptor signaling: Influence on adipogenesis. Mol. Cell. Biol., 27(20):7188-7197. http://www.citeulike.org/user/HEIRS/article/3787182