Arachidonic acid can significantly prevent early insulin resistance induced by a high-fat diet

To investigate whole-body metabolic disorder and hepatic glucose output (HGO) disturbance in rats with insulin resistance induced by a short-term high-fat diet, and the effect of arachidonic acid (AA).

Twenty-four normal male Wistar rats (230-250 g) were randomly divided into 3 groups according to their weight and fed for 12 weeks: control group, n = 8, fed with standard chow diet; high-fat (HF) group, n = 8, fed with a high-fat diet; HF+AA group, n = 8, fed with a high-fat diet and administered orally 3 mg x kg(-1) x day(-1)AA.

Early insulin resistance was successfully induced in HF-fed rats with hyperinsulinemia (p < 0.05), higher plasma triglyceride (TG) (p < 0.05), higher fasting liver glycogen content (p < 0.01) and higher glucose-insulin index (p < 0.01) during an oral glucose tolerance test (OGTT). The AA treatment significantly decreased the glucose-insulin index (p < 0.01), blood TG (p < 0.05) and glycogen content (p < 0.05) in liver. Both activity of phosphoenolpyruvate carboxykinase (PEPCK) (p < 0.05) and mRNA levels of PEPCK (p < 0.05) and glucose-6-phosphatase (G-6-Pase) (p < 0.01) in liver were also observed to be significantly decreased. But there were significant differences in the glucose-insulin index (p < 0.01) during OGTT, and glycogen content (p < 0.01) between the HF+AA and control groups.

AA can significantly prevent whole-body insulin resistance induced by a high-fat diet, as well as accompanied HGO disturbance in the overnight fasting state, but not thoroughly.