Title: The Aryl Hydrocarbon Receptor in Energy Balance: The Road from Dioxin-Induced Wasting Syndrome to Combating Obesity with Ahr Ligands.

Authors: Girer, Nathaniel G; Tomlinson, Craig R; Elferink, Cornelis J

Published In Int J Mol Sci, (2020 Dec 23)

Abstract: The aryl hydrocarbon receptor (AHR) has been studied for over 40 years, yet our understanding of this ligand-activated transcription factor remains incomplete. Each year, novel findings continually force us to rethink the role of the AHR in mammalian biology. The AHR has historically been studied within the context of potent activation via AHR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), with a focus on how the AHR mediates TCDD toxicity. Research has subsequently revealed that the AHR is actively involved in distinct physiological processes ranging from the development of the liver and reproductive organs, to immune system function and wound healing. More recently, the AHR was implicated in the regulation of energy metabolism and is currently being investigated as a potential therapeutic target for obesity. In this review, we re-trace the steps through which the early toxicological studies of TCDD led to the conceptual framework for the AHR as a potential therapeutic target in metabolic disease. We additionally discuss the key discoveries that have been made concerning the role of the AHR in energy metabolism, as well as the current and future directions of the field.

PubMed ID: 33374508

MeSH Terms: Animals; Dioxins/adverse effects; Disease Models, Animal; Disease Susceptibility; Drug Development; Energy Metabolism*/genetics; Gene Expression Regulation; Humans; Ligands; Mice, Transgenic; Molecular Targeted Therapy; Obesity/drug therapy; Obesity/etiology; Obesity/metabolism; Polychlorinated Dibenzodioxins/adverse effects; Receptors, Aryl Hydrocarbon/antagonists & inhibitors; Receptors, Aryl Hydrocarbon/genetics; Receptors, Aryl Hydrocarbon/metabolism*; Wasting Syndrome/etiology; Wasting Syndrome/metabolism