ATP/Adenosine, a type of neurotransmitter, has recently attracted attention as damage-associated molecular patterns (DAMPs) and has been reported to play an important role in the induction of inflammation via inflammasome. On the other hand, there have been few reports on in vivo measurements of ATP and adenosine in the synaptic cleft and/or extracellular spaces.Generally, in vivo measurement of neurotransmitter content in the synaptic cleft and/or extracellular spaces has been performed mainly by invasive methods such as micro dialysis. However, recently, GPCR-activation-based (GRAB) sensor was developed, which enhances the intensity of green fluorescent protein (GFP) fluorescence upon binding to specific neurotransmitters or neuromodulators (Sun F, Li Y et al. Cell, 2018).Therefore, we generated ATP- and Adenosine-specific GRAB sensor zebrafish (GRABATP and GRABAdo), examined the correlation between ATP/Adenosine dynamics in the extracellular space as DAMPs and the pathogenesis of metabolic liver diseases. Our results showed that ATP/Adenosine content in the extracellular space increased with progression of both alcoholic- and diet-induced fatty liver diseases. Furthermore, Clodronate, a vesicular nucleotide transporter inhibitor, was found to decrease ATP and adenosine content in the extrahepatic cellular space and to improve the disease state.　In this study, we used GRABATP and GRABAdo zebrafish models to show that extracellular ATP/Ado dynamics correlate with pathological progression of metabolic liver disease. We indicated for the first time that the neurotransmitters ATP and adenosine play an important role in the pathogenesis of these diseases as DAMPs, and that ATP/Adenosine dynamics is an indicator of metabolic liver disease.