In the current study, we investigated the effect of UA on mTOR signaling, we found that UA inhibits leucine-stimulated mTOR activation in C2C12 myotubes by inhibiting mTOR from targeting to lysosome, uncovering a novel mechanism underlying the negative regulation of the mTORC1 signaling pathway by UA, a small molecule that possess a wide range of beneficial properties including anti-hyperglycemia, anti-obesity, and anti-cancer. Here, MTOR is linked to obesity due to melanocortin 4 receptor deficiency.