Long-term supplementation of taurine induces hepatic steatosis and disrupts bile acid homeostasis in male mice.

Taurine, a sulfur-containing amino acid, is widely used in energy drinks and nutraceuticals. However, the long-term effects of taurine supplementation on liver metabolism remain incompletely understood. Here, male C57BL/6 mice were administered 3 % taurine in drinking water for 32 weeks. Taurine treatment reduced body weight and abdominal fat, suggesting potential anti-obesity effects. However, hepatic lipid accumulation and steatosis were evident in taurine-treated mice. Serum levels of alanine aminotransferase, alkaline phosphatase, cholesterol, non-esterified fatty acids (NEFA), total bile acids, and hepatic triglycerides were markedly elevated. Taurine significantly upregulated hepatic expression of the fatty acid transporter Cd36, thereby enhancing hepatic fatty acid uptake and promoting lipid deposition, while increasing lipolytic enzymes Atgl and Hsl expression in white adipose tissue, contributing to increased circulating NEFA and subsequent hepatic lipid accumulation. Moreover, taurine disrupted the negative feedback regulation of bile acid biosynthesis in the enterohepatic circulation, increased bile acid synthesis and uptake, altered bile acid transport, and elevated both conjugated and unconjugated bile acid species. Histological and molecular analyses further revealed taurine-induced hepatic inflammation, characterized by perivascular immune cell infiltration and upregulation of pro-inflammatory cytokines and mediators. Importantly, taurine-induced metabolic alterations in lipid and bile acid homeostasis were evident as early as 5 weeks, preceding the onset of histological steatosis. Collectively, these findings demonstrate that prolonged taurine supplementation promotes hepatic steatosis and inflammation, accompanied by dysregulation of bile acid homeostasis. The study highlights the potential metabolic risks associated with chronic taurine intake and underscores the need for caution when considering taurine-based health supplements.