Oleanolic Acid Targets the Gut-Liver Axis to Alleviate Metabolic Disorders and Hepatic Steatosis

This study investigated the effects of oleanolic acid (OA) on hepatic lipid metabolism and gut-liver axis homeostasis in an obesity-related non-alcoholic fatty liver disease (NAFLD) nutritional animal model and explored possible molecular mechanisms behind its effects. The results revealed that OA ameliorated the development of metabolic disorders, insulin resistance, and hepatic steatosis in obese rats. Meanwhile, OA restored high-fat-diet (HFD)-induced intestinal barrier dysfunction and endotoxin-mediated induction of toll-like-receptor-4-related pathways, subsequently inhibiting endotoxemia and systemic inflammation and balancing the homeostasis of the gut-liver axis. OA also reshaped the composition of the gut microbiota of HFD-fed rats by reducing the Firmicutes/Bacteroidetes ratio and increasing the abundance of butyrate-producing bacteria. Our results support the applicability of OA as a treatment for obesity-related NAFLD through its anti-inflammatory, antioxidant, and prebiotic integration responses mediated by the gut-liver axis.