Abstract: Objective: To explore the effect of citric acid (CA) on the regulation of blood lipids and insulin sensitivity in hyperlipidemic mice. Methods: KM mice were used to establish a hyperlipidemic animal model. Xuezhikang, a lipidlower drug in China, was used as a positive control, and low, medium and high-dose citric acid was given orally to the mouse model. Blood lipids and insulin levels were measured by commercial kits. The mRNA expression levels of glucose- 6-phosphatase (G-6-Pase) in liver and glucose transporter-4 (GLUT-4) in skeletal muscle were measured by reverse transcription-polymerase chain reaction (RT-PCR) to evaluate the effect of citric acid on blood lipids and insulin sensitivity in hyperlipidemic mice. Results: Compared with the blank control, the serum levels of triglyceride (TG), total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) in the hyperlipidemic model (HM) group was significantly increased, and serum HDL-C was significantly reduced (P < 0.01). Contrary results were observed when comparing the citric acid intervention and positive control groups with the HM group (P < 0.01), while there was no significant difference between the former ones and the blank control (P > 0.05). Compared with all other groups, fasting blood glucose (FBG) and 2 h postoral glucose tolerance test glucose levels were significantly higher in the HM group (P < 0.01), and glucose metabolism was significantly lower (P < 0.01). Fasting insulin (FIN) and homeostatic model assessment of insulin resistance (HOMA-IR) in the HM group were significantly higher and insulin sensitivity index (ISI) was significantly lower than in the blank control (P < 0.01). FIN, HOMA-IR and ISI in the citric acid intervention and positive control groups were different from those in the HM group; citric acid significantly increased ISI and decreased FIN and HOMA-IR (P < 0.01, P < 0.01 and P < 0.05 at high dose; P < 0.05, P < 0.05 and P < 0.05 at medium dose; P < 0.05, P < 0.01 and P < 0.05 at low dose) compared with the HM group, whereas all three dose groups showed no significant difference from the blank control (P > 0.05). The expression of G-6-Pase mRNA in liver in the HM group was significantly higher than in the blank control group (P < 0.01) and the citric acid intervention and positive control groups (P < 0.05 ), whereas the opposite was observed for the expression of GLUT-4 mRNA in skeletal muscle in the HM group versus the other groups. Conclusion: Citric acid can regulate blood lipid levels and improve insulin sensitivity in hyperlipidemic mice.

Key words: citric acid, hyperlipidemia, insulin sensitivity