ADORA2A and metabolic dysfunction-associated steatohepatitis: Peng et al. (2009) found that ethanol metabolism might induce intracellular and extracellular adenosine accumulation, which triggers ethanol-induced hepatic steatosis through A1 and A2B receptors. A2AR stimulation would protect from the development of NASH (Alchera et al., 2017), and A2AR disruption augment the process of NAFLD in mice (Cai et al., 2018). A3R agonist treatment also alleviated NASH in mice (Fishman et al., 2019). Overall, these findings suggest that metabolism of extracellular ATP plays important roles in maintaining glucose and lipid homeostasis (Figure 1).