Molecular identification and functional characterization of glucose-dependent insulinotropic peptide (GIP) and its...

As the cheapest feed ingredient, carbohydrates exert a protein-sparing effect. However, excessive carbohydrate intake can induce hepatic metabolic disorders and lead to metabolic diseases in fish. The GIP/GIPR axis plays a vital role in regulating lipid metabolism and glucose uptake. To evaluate the functions of GIP and GIPR in largemouth bass, we cloned their cDNA sequences. We analysed the tissue-specific expression of both genes and assessed the role of GIP in regulating glucose and lipid metabolism using hepatocyte studies and GIP interference assays. The largemouth bass gip gene (318 bp) encodes a protein of 105 amino acids, whereas the gipr gene (1614 bp) encodes a protein of 537 amino acids. Tissue distribution analysis revealed high expression of gip mRNA in the stomach. Additionally, gipr mRNA was highly expressed in the brain, foregut, midgut and hindgut. Both high-carbohydrate and high-fat intake in largemouth bass resulted in higher gip mRNA in the stomach and lower gipr mRNA expression in the foregut. Primary hepatocyte experiments showed that GIP treatment increased the expression of g6pase, acc1 and fas and decreased the expression of gk, pfk, hsl and lpl. Intraperitoneal injection of GIP small interfering RNA (siRNA) demonstrated that inhibiting GIP expression significantly reduced serum glucose and triglyceride levels. It also decreased the hepatic expression of g6pase, fbp1, pygl, acc1, fas and lpl, while increasing the expression of gys2 and hsl. These results suggest that GIP and GIPR regulate glucose and lipid metabolism in largemouth bass.