Department of Pharmacology and Toxicology, The University of Texas Medical Branch at Galveston, Galveston, TX 77550, USA.
Department of Molecular and Systems Biology, Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, Dartmouth College, Lebanon, NH 03756, USA.
Int J Mol Sci. 2020 Dec 23;22(1):49. doi: 10.3390/ijms22010049.
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--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.
芳烃受体 (AHR) 的研究已经超过 40 年，但我们对这种配体激活转录因子的理解仍不完整。每年，新的发现都迫使我们重新思考 AHR 在哺乳动物生物学中的作用。AHR 一直以来都是在通过 AHR 激动剂 2,3,7,8-四氯二苯并二恶英 (TCDD) 进行有力激活的背景下进行研究的，重点是 AHR 如何介导 TCDD 的毒性。随后的研究表明，AHR 积极参与从肝脏和生殖器官的发育到免疫系统功能和伤口愈合等不同的生理过程。最近，AHR 被牵涉到能量代谢的调节中，并被作为肥胖症的潜在治疗靶点进行研究。在这篇综述中，我们追溯了 TCDD 的早期毒理学研究如何导致 AHR 作为代谢疾病潜在治疗靶点的概念框架。我们还讨论了在能量代谢中 AHR 作用的关键发现，以及该领域的当前和未来方向。
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