Differential pathways to hepatic steatosis in fish: Divergent molecular mechanisms underlying high-carbohydrate versus high-lipid diet-induced lipid accumulation

High-carbohydrate and high-lipid diets are common high-energy diets that can reduce the protein consumption of fish and increase protein deposition in fish. However, long-term high-energy diets lead to liver steatosis and affect fish health. Fish utilize carbohydrates and fats differently, thus it is necessary to explore the differential effect of high-carbohydrate and high-lipid diets on abnormal liver fat deposition. Three isonitrogenous diets, including the control diets (CD), high-carbohydrate diets (HCD), and high-lipid diets (HFD), were formulated. Here, we reported that no differences were observed in the weight growth rate (WGR), condition factor (CF), and viscerosomatic index (VSI) of fish fed with high-energy diets compared to the control diets. High-lipid and high-carbohydrate diets increased the intraperitoneal fat ratio (IPF) and hepatosomatic index (HSI), respectively. In vivo and in vitro, biochemical parameters demonstrated that long-term high-energy diets caused liver damage in fish, increased liver or hepatocyte triglyceride content by more than 100 %, and inhibited VLDL secretion into plasma or medium. Oil red O staining also confirmed that high-energy diets significantly enhanced the liver lipid area of fish. In terms of ultrastructure, we found that high-carbohydrate diets increased the number of lipid droplets, while high-lipid diets increased the size and number of lipid droplets. Furthermore, high-lipid diets significantly up-regulated the gene or protein expressions related to fat synthesis, endoplasmic reticulum stress, and VLDL assembly in vivo and in vitro, while high-carbohydrate diets only up-regulated the expression of fat synthesis-related genes. These results indicated that high-carbohydrate diets induced hepatic fat deposition mainly through fat synthesis, but high-lipid diets promoted fat synthesis and inhibited VLDL secretion induced by endoplasmic reticulum stress. This study provides a molecular pathway for targeting hepatic steatosis caused by different energy diets.