Different regulation of branched-chain amino acid on food intake by TOR signaling in Chinese perch (Siniperca chuatsi)

Abstract The mTOR signaling pathway integrates energy status with hormonal signals to regulate not only protein synthesis and growth, but also food intake and energy balance. However, the involvement of TOR signaling pathway in food intake regulation is not clearly characterized in fish. To investigate whether TOR signaling is integrated with both hypothalamic neuronal activity and peripheral signaling in Chinese perch (Siniperca chuatsi), intracerebroventricular administration of branched-chain amino acid (BCAA: leucine, valine and isoleucine) and the inhibitor of TOR signaling rapamycin were performed to detect the regulation of TOR signaling on food intake. The results showed that only leucine could stimulate the TOR signaling, but valine and isoleucine inhibit the TOR signaling. The three BCAA also showed different effects on the food intake and the expression of appetite control genes (hypothalamic neuronal signaling: npy, agrp, pomc, and peripheral hormone: ghrelin, leptin). The up-regulation or down-regulation of TOR signaling by leucine or valine, might suppress or stimulate the food intake through modulating the protein levels of anorexigenic POMC, respectively. We also found the same effects of leucine, valine or isoleucine on the TOR signaling and appetite gene expression in the primary brain cells of Chinese perch. In addition, the different regulation of BCAA on TOR signaling could be attributed to the regulation of BCAA on the interaction between SESN2 and GATOR. These results indicate that three BCAA exhibit the different regulatory roles on the TOR signaling and food intake in fish, unlike in mammals, BCAA activate mTOR signaling.