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Biochem Pharmacol. 2019 Aug 26;169:113620. doi: 10.1016/j.bcp.2019.08.022. [Epub ahead of print]

Functions of aryl hydrocarbon receptor (AHR) and CD38 in NAD metabolism and nonalcoholic steatohepatitis (NASH).

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Institute of Experimental and Clinical Pharmacology and Toxicology, Wilhelmstrasse 56, D-72074 Tübingen, Germany. Electronic address:


Aryl hydrocarbon receptor (AHR), identified in studies of dioxin toxicity, has been characterized as ligand-activated transcription factor involved in diverse functions including microbial defense, cell proliferation, immunity and NAD metabolism. AHR targets of the latter function are PARPs/ARTs and CD38 that are regulating glucose and lipid metabolism via NAD-dependent sirtuins. Deregulation of these pathways may facilitate obesity and age-dependent pathologies. The present commentary is focused on AHR and CD38 signaling in liver. CD38 is functioning as ectoNADase and Ca2+ mobilizing enzyme in endoplasmic reticulum and endolysosomal membranes. Deregulation of TCDD-activated AHR and CD38 may facilitate hepatic steatosis and inflammation. However, these proteins are also involved in protection against inflammation and CD38-mediated age-related decreased NAD levels that may be responsible for neurodegeneration. Further knowledge about the complexity of these pathways is needed to avoid pathologies. Therapeutic modulation of AHR and CD38 remains a challenging task.


2,3,7,8-Tetrachlorodibenzo-p-dioxin = TCDD (PubChem 15625); AHR, CD38, NAD metabolism; Hepatic steatosis; NASH; Nicotinamide (PubChem CID 936); Nicotinamide adenine dinucleotide = NAD (PubChem CID 5893); Nicotinamide riboside (PubChem CID 439924)


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