Sequential Activations of ChREBP and SREBP1 Signals Regulate the High-Carbohydrate Diet-Induced Hepatic Lipid Deposition in Gibel Carp (Carassius gibelio)

The present study investigated the sequential regulation signals of high-carbohydrate diet (HCD)-induced hepatic lipid deposition in gibel carp (Carassius gibelio). Two isonitrogenous and isolipidic diets, containing 25% (normal carbohydrate diet, NCD) and 45% (HCD) corn starch, were formulated to feed gibel carp (14.82 & PLUSMN; 0.04 g) for 8 weeks. The experimental fish were sampled at 2(nd), 4(th), 6(th), and 8(th) week. In HCD group, the hyperlipidemia and significant hepatic lipid deposition (oil red O area and triglyceride content) was found at 4(th), 6(th), and 8(th) week, while the significant hyperglycemia was found at 2(nd), 4(th), and 8(th) week, compared to NCD group (P<0.05). HCD induced hepatic lipid deposition via increased hepatic lipogenesis (acc, fasn, and acly) but not decreased hepatic lipolysis (hsl and cpt1a). When compared with NCD group, HCD significantly elevated the hepatic sterol regulatory element binding proteins 1 (SREBP1) signals (positive hepatocytes and fluorescence intensity) at 4(th), 6(th), and 8(th) week (P<0.05). The hepatic SREBP1 signals increased from 2(nd) to 6(th) week, but decreased at 8(th) week due to substantiated insulin resistance (plasma insulin levels, plasma glucose levels, and P-AKT(Ser473) levels) in HCD group. Importantly, the hepatic carbohydrate response element binding protein (ChREBP) signals (positive hepatocytes, fluorescence intensity, and expression levels) were all significantly elevated by HCD-induced glucose-6-phosphate (G6P) accumulation at 2(nd), 4(th), 6(th), and 8(th) week (P<0.05). Compared to 2(nd) and 4(th) week, the hepatic ChREBP signals and G6P contents was significantly increased by HCD at 6(th) and 8(th) week (P<0.05). The HCD-induced G6P accumulation was caused by the significantly increased expression of hepatic gck, pklr, and glut2 (P<0.05) but not 6pfk at 4(th), 6(th), and 8(th) week, compared to NCD group. These results suggested that the HCD-induced hepatic lipid deposition was mainly promoted by SREBP1 in earlier stage and by ChREBP in later stage for gibel carp. This study revealed the sequential regulation pathways of the conversion from feed carbohydrate to body lipid in fish.