We aimed to investigate whether phloridzin could alleviate nonalcoholic fatty liver disease (NAFLD) in mice, which was induced by feeding a high-fat diet (HFD). We initially analyzed the effect of phloridzin on alleviating HFD-induced NAFLD in C57BL/6J mice and oleic acid (OA)-stimulated human normal liver L-02 cells (L02). Then, we investigated the mechanism of phloridzin on the mTORC1/sterol-regulatory element-binding protein-1c (SREBP-1c) signaling pathway by siRNA analysis, qRT-PCR, flow cytometry, and western blot analysis in vivo and in vitro. The results revealed that phloridzin significantly inhibited the increase in body weight, alleviated abnormal lipid metabolism, and decreased lipid biosynthesis and insulin resistance. Moreover, phloridzin augmented the number of CD8+CD122+PD-1+ Tregs and CD4+FoxP3+ Tregs in HFD-fed C57BL/6J mice and HFD-fed aP2-SREBF1c mice and downregulated the mTORC1/SREBP-1c signaling pathway-related protein expressions in vivo and in vitro. Furthermore, phloridzin reduced the expression of SREBP-1c in SREBP-1c-RNAi-lentivirus-transfected L02 cells and reversed the SREBP-1c expression in HFD-fed aP2-SREBF1c transgenic mice. Phloridzin ameliorates lipid accumulation and insulin resistance via inhibiting the mTORC1/SREBP-1c pathways. These results indicated that phloridzin may actively ameliorate NAFLD.
Keywords: NAFLD; SREBP-1c; Treg; mTORC1; phloridzin.