Osthol attenuates hepatic steatosis via decreased triglyceride synthesis not by insulin resistance

摘要

AIM: To evaluate the effects of osthol on intrahepatic fat synthesis, β-oxidation, inflammation, and insulin resistance by multifaceted analysis.METHODS: Sprague-Dawley rats(n = 30) were randomly divided into control, non-alcoholic fatty liver disease(NAFLD), and osthol groups. NAFLD and osthol groups were fed with a high-fat diet for 14 wk. After 8 wk of the high-fat diet, the osthol group also received osthol 20 mg/kg orally 5 times/wk. To assess the insulin resistance, oral glucose tolerance was performed at the end of 14 wk. Immunohistochemical(4-HNE, F4/80) and hematoxylin and eosin(HE) staining wereperformed on liver tissue extracts after animal sacrifice at 14 wk. SREBP1 c, FAS, SCD-1, PPAR-α, CROT, MCP-1, IRS-1, and IRS-2 mRNA expressions were assessed with reverse transcription-polymerase chain reaction.RESULTS: HE staining revealed that, compared with the NAFLD group, the osthol group showed significantly decreased intrahepatic fat content(39.4% vs 21.0%; P = 0.021). SREBP1 c expression in the NAFLD group increased compared to controls(P = 0.0001), while osthol treatment decreased SREBP1 c expression compared with the NAFLD group(P = 0.0059). In the osthol group, intrahepatic FAS and SCD-1, which act downstream of SREBP1 c, decreased significantly compared with the NAFLD group. Moreover, PPAR-α expression in the osthol group was also significantly higher than in the NAFLD group(P = 0.0147).CONCLUSION: Osthol treatment attenuated liver steatosis by decreasing de novo liver triglyceride synthesis and had nominal effects on insulin resistance and liver inflammation.