Long-term supplementation of umbelliferone and 4-methylumbelliferone alleviates high-fat diet induced hypertriglyceridemia and hyperglycemia in mice

• Umbelliferone and 4-methylumbelliferone reduced hypertriglyceridemia in obese mice.
• Umbelliferone and 4-methylumbelliferone improved glucose tolerance in obese mice.
• Umbelliferone and 4-methylumbelliferone increased plasma adiponectin levels in obese mice.
• Umbelliferone and 4-methylumbelliferone modulated hepatic lipid metabolism in obese mice.
• Umbelliferone and 4-methylumbelliferone enhanced hepatic antioxidant system in obese mice.

This study was conducted to evaluate the effects of umbelliferone (UF) and 4-methylumbelliferone (mUF) on high-fat diet-induced hypertriglyceridemia and hyperglycemia in mice. The mice were assigned to normal control, high-fat control, and high-fat with UF or mUF groups. For UF or mUF groups, the high-fat diet was supplemented with UF or mUF at 0.02% (wt/wt) for 12 weeks. Both UF and mUF significantly decreased plasma triglyceride, free fatty acid and glucose levels, adipocyte size, white adipose tissue weights, and hepatic phosphatidate phosphohydrolase activity and significantly increased plasma adiponectin levels and hepatic fatty acid β-oxidation activity compared with the high-fat control group. UF and mUF improved glucose intolerance and hepatic steatosis in the high-fat fed mice. Long-term high-fat diet intake induced an increase in hepatic CYP2E1 activity and lipid peroxide and cytosolic hydrogen peroxide contents and suppressed superoxide dismutase and glutathione peroxidase activities, which were reversed by UF and mUF supplementation. These results indicate that UF and mUF similarly ameliorate hypertriglyceridemia and hyperglycemia partly by modulating hepatic lipid metabolism and the antioxidant defense system along with increasing adiponectin levels.