Accumulative lines of evidence reveal that AMPK activation causes a down-regulation of PI3K/Akt/mTOR pathway in cancer cells [39,40], Thus, our data suggest that miltefosine may antagonize HFD-induced disorder in glycolipid metabolism and insulin resistance via activation of AMPK and inhibition of PI3K/AKt/mTOR pathway. Here, AKT1 is linked to cancer.