The regulation of rapamycin on nutrient metabolism in Nile tilapia fed with high-energy diet

Abstract

High energy diets (HED) have been widely used in farmed fish, but HED also caused some metabolic diseases. The rapamycin-induced inhibition of mechanistic target of rapamycin (mTOR) signalling has been verified to alleviate metabolic syndromes in mammals, however, the functions of rapamycin in regulating metabolism in the fish fed with HED has not been well investigated. In the present 8-week feeding trial, Nile tilapia were fed with a normal diet with medium fat and medium carbohydrate (MFMC), a high fat and high carbohydrate (HFHC) diet, or the HFHC diet supplemented with rapamycin (Rap). Compared to MFMC diet, the HFHC diet significantly increased phosphorylation of mTOR protein, lipid deposition in tissues, glycogen degradation, oxidative stress and inflammation, but decreased lipid catabolism capability. The supplementation of Rap in the HFHC diet inhibited phosphorylation of mTOR protein and protein synthesis, but elevated protein catabolism. Rap addition also increased catabolism of lipid and carbohydrate, reduced oxidative stress and inflammation, and promoted autophagic activities, meaning Rap addition could alleviate the most of the adverse effects caused by the HFHC diet. All these indicate that the elevated mTOR activity was highly correlated to the adverse effects of HFHC diet on physiological functions in fish, and the inhibition of mTOR activity could largely help to maintain normal physiological status in the HED-fed fish. Therefore, mTOR could be a promising regulatory target to alleviate the metabolic dysfunctions caused by HED in fish, however, the possible negative effects of TOR pathway regulation on protein retention and growth should also be carefully evaluated in practices.