High-fat diet induces aberrant hepatic lipid secretion in blunt snout bream by activating endoplasmic reticulum stress-associated IRE1/XBP1 pathway

Abstract

This study was conducted to understand the effect of high-fat diet challenge on lipid transport and endoplasmic reticulum stress in blunt snout bream. Ninety fish (average weight: 41.84 ± 0.07 g) were randomly fed a control diet (6% fat) or a high-fat diet (11% fat) for 9 weeks. The growth performance and feed utilization efficiency were evaluated at the end of the trial. The liver samples of both groups were harvested for molecular analysis and histological evaluation. Compared to the Control group, the high-fat diet group showed no effects on either growth performance or energy intake in blunt snout bream. However, high-fat diet resulted in a massive accumulation of lipid and pathological structural alternations, and disrupted expression of lipid transport-related genes and endoplasmic reticulum stress in the liver of the fish. In vitro, after exposure of the isolated primary hepatocytes from blunt snout bream to oleic acid, the cells showed increased intracellular TG accumulation, decreased VLDL secretion, which was attributed to altered expression levels of lipid transport-related genes through the activated IRE1/XBP1 signaling. The oleic acid-induced detrimental effects were alleviated by co-incubating the cells with an IER1 inhibitor, 4μ8c. In conclusion, high-fat diet could lead to aberrant lipid secretion by activating the ER stress-associated IRE1/XBP1 pathway. Inhibiting the activity of IRE1 represents a promising target to rescue the side-effects of high-fat diet on the liver function of blunt snout bream.