Role of Hepatic Aryl Hydrocarbon Receptor in Non-Alcoholic Fatty Liver Disease
Nikhil Y. Patil, Jacob E. Friedman, Aditya Joshi
Abstract
Numerous nuclear receptors including farnesoid X receptor, liver X receptor, peroxisome proliferator-activated receptors, pregnane X receptor, hepatic nuclear factors have been extensively studied within the context of non-alcoholic fatty liver disease (NAFLD). Following the first description of the Aryl hydrocarbon Receptor (AhR) in the 1970s and decades of research which unveiled its role in toxicity and pathophysiological processes, the functional significance of AhR in NAFLD has not been completely decoded. Recently, multiple research groups have utilized a plethora of in vitro and in vivo models that mimic NAFLD pathology to investigate the functional significance of AhR in fatty liver disease. This review provides a comprehensive account of studies describing both the beneficial and possible detrimental role of AhR in NAFLD. A plausible reconciliation for the paradox indicating AhR as a 'double-edged sword' in NAFLD is discussed. Finally, understanding AhR ligands and their signaling in NAFLD will facilitate us to probe AhR as a potential drug target to design innovative therapeutics against NAFLD in the near future.