Okra polysaccharide activates PPAR-γ signaling to attenuate metabolic-associated fatty liver disease in mice.

Previous investigations demonstrated that okra polysaccharide (OP) ameliorated hepatocellular lipotoxicity in vitro. However, the therapeutic efficacy and molecular mechanisms involved in metabolic-associated fatty liver disease (MAFLD) require further elucidation. To address this gap, two murine models of MAFLD, obese Ob/Ob mice and high fat/cholesterol/fructose (HFCF) fed-mice, were utilized. The therapeutic implications of OP supplementation were evaluated by quantifying lipid-specific biomarkers and conducting hepatic histopathological examinations. Complementary transcriptomic, phosphoproteomic, and in vitro analyses were performed to unravel the molecular mechanisms. In the Ob/Ob mouse model, OP significantly reduced both circulating and hepatic lipid levels while ameliorating hepatic steatosis. In the HFCF-induced MAFLD model, OP not only attenuated hepatic lipid accumulation but also mitigated concurrent inflammation and fibrosis. Subsequent RNA-sequencing analyses on hepatic tissues from HFCF-diet mice revealed that OP modulated MAFLD-associated transcriptional signatures. A combined assessment of transcriptomics and phosphoproteomics highlighted OP's significant impact on the Peroxisome Proliferator-Activated Receptor (PPAR) pathway, particularly through the upregulation of PPAR-γ signaling. In murine hepatocytes, OP counteracted steatosis and inflammation via PPAR-γ signaling activation. These effects were abolished upon administration of the PPAR-γ-specific antagonist GW9662. Collectively, our empirical evidence provides the inaugural demonstration that OP mitigates MAFLD pathology through the activation of PPAR-γ signaling, presenting a novel therapeutic avenue for MAFLD intervention.