TY - JOUR
T1 - The aryl hydrocarbon receptor in energy balance
T2 - The road from dioxin-induced wasting syndrome to combating obesity with AHR ligands
AU - Girer, Nathaniel
AU - Tomlinson, Craig R.
AU - Elferink, Cornelis J.
N1 - Funding Information:
Funding: This work was supported by the Norris Cotton Cancer Center Prouty Pilot Award (C.R.T.) and the following NIH grants: F32DK116489 (N.G.G.), 5P30CA023108-41 (C.R.T.), 5P20RR024475-02 (C.R.T.), 8P20GM103534-02 (C.R.T.), R01ES026874 (C.J.E.), and P30ES030285 (C.J.E.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Institutional Review Board Statement: Not applicable. Informed Consent Statement: Not applicable. Data Availability Statement: Data sharing not applicable.
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/1/1
Y1 - 2021/1/1
N2 - 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.
AB - 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.
KW - Aryl hydrocarbon receptor
KW - Energy metabolism
KW - Obesity
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U2 - 10.3390/ijms22010049
DO - 10.3390/ijms22010049
M3 - Review article
C2 - 33374508
AN - SCOPUS:85098633935
SN - 1661-6596
VL - 22
SP - 1
EP - 13
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 1
M1 - 49
ER -