Taken that HDL and apoA-I has direct anti-obesity effect in rat and that HDL activate PI3K-Akt signaling which negatively regulate autophagy through mTORC1, we propose that HDL/apoA-I inhibit autophagy through PI3K-Akt signaling, leading to phenotype transition of white adipocyte. This evidence concerns the gene AKT1 and obesity due to melanocortin 4 receptor deficiency.