LAUSR

Graphical abstract Figure. No caption available. &NA; Diverse physiologic functions of AHR, a transcription factor discovered in studies of dioxin toxicity, are currently elucidated in many laboratories including chemical and microbial defense, immunity and myelopoiesis. Accumulating evidence suggests that AHR may also be involved in obesity and TCDD‐mediated lethality in sensitive species. Underlying mechanisms include NAD+‐ and sirtuin‐mediated deregulation of lipid, glucose and NAD+ homeostasis. Progress in NAD metabolome research suggests large consumption of NAD+ by NAD glycohydrolases (NADases) and NAD‐dependent sirtuins. In focus are two NADases: (i) TiPARP (TCDD‐induced poly(ADP‐ribose) polymerase), one of several nuclear NADases, and (ii) plasma membrane‐bound ectoNADase/CD38, a multifunctional enzyme and receptor. CD38 is involved in extra‐ and intracellular NAD degradation but acts also as differentiation marker. Both CD38 and AHR are components of a complex signalsome that enhances retinoic acid‐induced differentiation of myeloid progenitor cells to granulocytes. Further advances of NAD metabolome research may lead to therapeutic options in the control of obesity and to improved risk assessment of TCDD toxicity.