Glucolipid metabolism of lipoprotein lipase heterozygous mice and the mechanism of insulin resistance / 中华内分泌代谢杂志

ABSTRACT

Objective To investigate the glucolipid metabolism in lipoprotein lipase (LPL) gene knockout mice, and to explore the possible mechanisms of insulin resistance. Methods 16- and 40-week old LPL gene knockout heterozygous mice( LPL + / -) and wild type ( WT) C57 mice were selected and divided into 4 groups16-week LPL+ / -(n=6), 16-week WT(n = 6), 40-week LPL+ / -(n = 6), and 40-week WT(n = 6) group. LPL activity of post-heparin serum was examined. Serum triglyceride( TG) and free fatty acid( FFA) were measuzed. Intraperitoneal glucose tolerance test(IPGTT) in 4 groups of mice were performed. The glucose area under the curve (AUCG) and homeostasis model assessment for insulin resistance index and β-cell function index ( HOMA-IR, HOMA-β) were calculated to evaluate insulin sensitivity and the function of islet β-cells. Serum malondialdehyde (MDA) and total antioxidant capacity ( TAOC) levels were determined by means of colorimetric method. Using dihydroethidium( DHE) fluorescent staining method, reactive oxygen species ( ROS) levels in liver and skeletal muscle were determined. Results LPL activity levels of both 16- and 40-week LPL+ / - mice were significantly lower than that in WT mice of the same age. Serum TG and FFA of 40-week old LPL+ / - mice were significantly higher than those in WT mice of the same age(P<0. 05), and they were also higher than those of 16-week old LPL+ / - mice(P<0. 05). IPGTT showed that compared with WT mice, blood glucose level in LPL+ / - mice was significantly higher than that in WT group at 30 and 120 minute(P<0. 05), and fasting insulin and HOMA-IR were increased significantly(P<0. 05). Serum MDA of 40-week old LPL+ / - mice was evidently higher than that in WT mice by the same week(P<0. 05), while TAOC level was lower than that of WT mice (P<0. 05). ROS in skeletal muscle of 16-week old LPL+ /- mice was significantly increased. Meanwhile, ROS in both liver and skeletal muscle of 40-week old LPL+ / - mice was significantly higher than that in WT mice of the same age. Conclusion As time goes by, lipid and glucose disorders of LPL+ / - mice are aggravating, and insulin resistance develops evidently. Insulin resistance in LPL+ / -mice with dyslipidemia may be related to oxidative stress.