Short-Chain Fatty Acids (SCFAs) Modulate the Hepatic Glucose and Lipid Metabolism of Coilia nasus via the FFAR/AMPK Signaling Pathway In Vitro

The expansion of intensive aquaculture has heightened metabolic dysregulation in fish caused by high-glucose and high-lipid (HG-HL) diets, contributing to growth retardation and hepatic pathologies. Using <i>Coilia nasus</i> hepatocytes, this study investigated the regulatory effects of short-chain fatty acids (SCFAs) on glucose-lipid metabolism. In vitro HG-HL exposure elevated intracellular glucose, triglycerides (TG), and cholesterol; suppressed catalase (CAT) and superoxide dismutase (SOD); and dysregulated metabolic genes (upregulated <i>phosphoenolpyruvate carboxykinase</i> and <i>acetyl-CoA carboxylase</i>; downregulated <i>glucokinase</i> and <i>hormone-sensitive lipase</i>). Co-treatment with acetate and propionate reversed these anomalies, reducing TG and cholesterol, restoring antioxidant capacity (SOD and CAT), and normalizing gene expression patterns. Molecular docking suggested potential binding interactions between SCFAs and free fatty acid receptor (FFAR2/3). This study provided initial evidence suggesting SCFAs might attenuate HG-HL-induced metabolic stress in a teleost model, potentially involving FFAR-related pathways and AMPK-associated responses. The findings contribute to understanding SCFA-mediated metabolic regulation in fish, offering preliminary support for developing dietary interventions to manage aquacultural metabolic syndromes.