Glucolipid metabolism of lipoprotein lipase heterozygous mice and the mechanism of insulin resistance

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 groups: 16-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 measured. 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. (Chin J Endocrinol Metab, 2015, 31: 143-147) Key words: Lipoprotein lipase; Insulin resistance; Oxidative stress