Umbelliferone Ameliorates Hepatic Steatosis and Lipid-Induced ER Stress in High-Fat Diet-Induced Obese Mice

Purpose: Among the characteristics of non-alcoholic fatty liver disease (NAFLD), hepatic steatosis is due to excessive fat accumula-tion and causes liver damage and lipotoxicity, which are associated with insulin resistance, endoplasmic reticulum (ER) stress, and apoptosis. Umbelliferone (UMB) has various powerful pharmacological properties, such as antioxidant, anti-hyperglycemic, anti-viral, and anti-inflammatory effects. However, the mechanism of action in hepatic steatosis and lipid-induced ER stress is still unclear. Thus, the efficacy of UMB in hepatic steatosis and palmitate (PA)-induced hepatocellular lipotoxicity was evaluated in the present study.Materials and Methods: Male C57BL/6J mice (n=40) were divided into four groups: regular diet (RD), UMB-supplemented RD, high-fat diet (HFD), and UMB-supplemented HFD. All mice were fed orally for 12 weeks. In addition, the effects of UMB on lipo-toxicity were investigated in AML12 cells treated with PA (250 mu M) for 24 h; Western blot analysis was used to evaluate the chang-es in ER stress and apoptotic-associated proteins.Results: Administration with UMB in HFD-fed mice reduced lipid accumulation and hepatic triglyceride (TG) as well as serum insulin and glucose levels. In AML12 cells, UMB treatment reduced lipid accumulation as indicated by decreases in the levels of lipogenesis markers, such as SREBP1, FAS, PPAR-gamma, and ADRP. Furthermore, UMB reduced both oxidative stress and ER stress-re-lated cellular apoptosis.Conclusion: UMB supplementation ameliorated hepatic steatosis and improved insulin resistance by inhibiting lipid accumula-tion and regulating ER stress. These findings strongly suggest that UMB may be a potential therapeutic compound against NAFLD.

Automated summary

This study evaluated the efficacy of umbelliferone in hepatic steatosis and palmitate-induced hepatocellular lipotoxicity. The results showed that umbelliferone improved insulin resistance by inhibiting lipid accumulation and regulating endoplasmic reticulum stress. These findings suggest that umbelliferone may be a potential therapeutic compound against non-alcoholic fatty liver disease.