The objectives of this study were to determine the effect of
osthole on the
insulin resistance (IR) in high-fat and high-
sucrose-induced
fatty liver rats and to investigate its potential mechanisms. The rat model was established by orally feeding high-fat and high-
sucrose emulsion by gavage for 9 weeks. The experimental rats were treated with
osthole 5 and 10 mg/kg,
lipanthyl 30 mg/kg, and
rosiglitazone 4 mg/kg after oral high-fat and high-
sucrose emulsion for 6 weeks and were sacrificed 4 weeks after administration. The total
cholesterol (TC),
triglycerides (TG), and
free fatty acids (FFA) in serum and hepatic tissue, fasting
blood glucose (FBG), fasting serum
insulin (FINS), serum
adiponectin, and liver weight were measured. The homeostasis model assessment of
insulin resistance (HOMA-IR) and coefficient of hepatic weight were calculated. The results showed that
after treatment with
osthole, the serum levels of TC, TG, and FFA, the contents of TG and FFA in hepatic tissue, and
body weight gain were lowered, especially in the
osthole 10 mg/kg group (p < 0.05 or p < 0.01). Moreover, the histological evaluation of liver specimens demonstrated that the steatosis and
inflammation in liver in
osthole-treated groups were improved, especially in the 10 mg/kg group (p < 0.05). Importantly, the levels of FBG, FINS, and HOMA-IR in the
osthole 10 mg/kg group were decreased (p < 0.01), while the level of serum
adiponectin in the
osthole-treated groups, like
PPAR α agonist
lipanthyl and
PPAR γ agonist
rosiglitazone, was increased (p < 0.05). These results revealed that
osthole could improve the IR induced by high-fat and high-
sucrose emulsion in
fatty liver rats, and its mechanism might be associated with increment of
adiponectin release via activation of
PPAR α/ γ pathway.