Secondary bile acids impact hepatic energy metabolism in rainbow trout, <i>Oncorhynchus mykiss</i>

In recent years, secondary bile acids (SBAs) have emerged as key signalling molecules influencing energy balance, feed intake and glucose and lipid homeostasis in mammals, yet their physiological roles in fish are still poorly understood. This study investigated the short-term effects - 6 h post-intragastric administration - of SBAs [500 µmol l-1 lithocholic acid (LCA), 1500 µmol l-1 deoxycholic acid (DCA) and their taurine conjugates: 1000 µmol l-1 T-LCA and 600 µmol l-1 T-DCA] on hepatic metabolism in rainbow trout. Specifically, we assessed mRNA abundance and activity of hepatic enzymes involved in glucose and lipid metabolism, and expression of metabolic regulators, circulating and hepatic metabolites, and hepatic genes related to BA transport, receptors and synthesis. Our results revealed that LCA potentially inhibits hepatic gluconeogenesis by reducing the enzymatic activity of glucose 6-phosphatase (G6pase), fructose 1,6-bisphosphatase (Fbpase) and phosphoenolpyruvate carboxykinase (Pepck), combined with prkaa1 (Ampk) upregulation and foxo1 downregulation. However, these molecular effects did not translate in this treatment into consistent changes in plasma or hepatic glucose levels. As for lipid metabolism, DCA increased the mRNA abundance of lipogenesis markers (acly, acc) and prkaa1. At the enzymatic level, DCA reduced Cpt-1 activity, while Acly activity showed contradictory responses. Despite these molecular changes, hepatic lipid content remained stable, hindering a clear interpretation of the putative lipogenic effects. Bile acid transport and synthesis showed tightly regulated, SBA-specific responses, with LCA specifically upregulating cyp8b1 and inhibiting fxr. Overall, these findings underscore the structural specificity and species dependence of SBA signalling in teleosts and highlight the importance of SBA identity and temporal dynamics in shaping metabolic regulation in fish.