Papaya Leaf Extract Ameliorates Hepatic Steatosis in High‐Fat Diet–Induced Obese Mice and Oleic Acid–Stimulated HepG2 Cells

Hepatic steatosis, characterized by the accumulation of lipids in hepatocytes, is a chronic stage of nonalcoholic fatty liver disease (NAFLD). Papaya ( Carica papaya L.), belonging to the Caricaceae family, possesses therapeutic and nutritional properties. Notably, papaya leaves have medicinal properties; however, their effect on hepatic steatosis remains to be elucidated. Therefore, in this study, we investigated the ameliorative effect of papaya leaf extract (PLE) on hepatic steatosis using a high‐fat diet (HFD)–induced obese mice and oleic acid (OA)–treated HepG2 cells. Administration of PLE ameliorated body weight gain and hepatic lipid accumulation in HFD‐induced obese mice. Furthermore, PLE decreased the expression of critical adipogenic markers, including CCAAT/enhancer‐binding protein α (C/EBP α ), sterol regulatory element‐binding protein 1 (SREBP‐1), and peroxisome proliferator‐activated γ (PPAR γ ), in the liver. The expression of phospho‐adenosine monophosphate‐activated protein kinase (p‐AMPK) increased in the liver of PLE‐administered mice. Consistent with the in vivo study, PLE reduced lipid accumulation and the protein expression of adipogenic factors and increased p‐AMPK expression in OA‐treated HepG2 cells. Collectively, these results indicate the potential of PLE as a therapeutic agent for obesity‐induced hepatic steatosis.