Arachidonoyl-taurine protects from diet-induced hepatic steatosis and inflammation

Metabolic dysfunction-associated steatotic liver disease and its progressive and inflammatory form metabolic dysfunction-associated steatohepatitis represents a global health challenge, with limited treatment options available. In this study we identified an endogenous, understudied omega-6 fatty acid metabolite, arachidonoyl-taurine (ARA-T), capable of mitigating liver disease. ARA-T levels increased in human plasma of chronic and acute fatty liver and their abundance can be driven in humans and mice by dietary supplementation of arachidonic acid. Surprisingly, our genetic model of elevated circulating ARA-T levels prevented inflammation and hepatic steatosis by increased uptake and turnover of fatty acids in the liver. Pharmacological administration of ARA-T reduced liver weight and diet-induced hepatic lipid deposition in mice, demonstrating its potential to protect against and reverse the progression of liver disease. Thus, ARA-T may represent a way to protect against pro-inflammatory actions of omega-6 fatty acids thereby contributing to regulation of inflammation and accumulation of hepatic lipids.