Abstract: Objective To investigate the role and mechanism of paraoxonase 1 (PON1) and lipid metabolism,insulin resistance in nonalcoholic fatty liver disease(NAFLD). Methods One hundred and twenty-nine NAFLD patients and 130 non-NAFLD individuals were enrolled in the study. The age, height, weight, waist circumference, blood pressure and other information were collected. Plasma blood lipids, fast glucose, and glucagon were detected by routine blood tests, homeostatic index of insulin resistance (HOMA-IR) was calculated, liver and kidney function were evaluated in biochemical assay, LO2 cells were inoculated in 12-well plates for 24 h and then added 0~ 1.2 mM OA solution was treated for 24 h or 10 ng/mL TNF-α for 6 h, and the 1 μg control and PON1 plasmid were transfected with PEI for 24 h. The intracellular lipid content was determined using a Nile Red dye. PON1 activity was detected by ELISA, and PON1, p-IRS1, T-IRS1, p-AKT T-AKT, FAS, HMGCR, SREBP2 and SREBP1C protein were detected by Western Blot. Results Waist circumference, BMI, peripheral blood ALT, AST, FFAs, TG, TC, LDL-C, VLDL-C, fasting blood glucose, insulin, HOMA-IR, resistin, leptin, IL-6 and TNF-α were significantly higher in patients with NAFLD. In non-NAFLD, PON1 activity, content, HDL-C, glucagon and adiponectin were significantly reduced; PON1 activity and content were significantly negatively correlated with FFAs, TG, TC, LDL-C, VLDL-C, fasting blood glucose, insulin, HOMA -IR, resistin, leptin, IL-6 and TNF-α, and positively correlated with HDL-C, glucagon and adiponectin; PON1 activity in LO2 cells of OA group gradually decreased, and the activity of PON1 in LO2 cells of 0.2~1.2 mM OA group was significantly lower than that of control group. Overexpression of PON1 did not affect PON1 activity, the lipid content of LO2 cells in 0.2~1.2 mM OA group was significantly higher. In the control group, it was significantly lower than the OA group; the expression levels of PON1, p-IRS1, p-AKT, FAS, HMGCR, SREBP2 and SREBP1C in the TNF-α group were significantly lower than those in the control group, and the transfected PON1 plasmid was significantly increased. PON1, while the expression levels of p-IRS1, p-AKT, FAS, HMGCR, SREBP2 and SREBP1C protein were significantly increased. Conclusion PON1 activity and content are significantly correlated with NAFLD lipid metabolism and insulin resistance, and may affect insulin resistance and regulate lipid metabolism by regulating p-IRS1/AKT pathway.

Key words: Nonalcoholic fatty liver disease, Paraoxonase 1, insulin resistance, lipid metabolism, IRS1/AKT pathway