Abstract:

Objective To observe the change of glucose metabolism and tissue-targeted (liver and skeletal muscle) insulin sensitivity in mice with hypertriglyceridemia or hypercholesterolemia. Methods Mice fed with normal diet (control group, n=8), lipoprotein lipase gene knockout heterozygous mice (LPL+/-) (hypertriglyceridemia group, n=8) and mice fed with high-fat diet (hypercholesterolemia group, n=8) were selected. Body weight of each group of mice was measured, serum triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), blood glucose and fasting insulin were detected, homeostasis model assessment of insulin resistance(HOMA-IR) and insulin sensitivity index (ISI) were calculated, and the change of phosphorylation of serine of Akt473 after insulin stimulation (relative expression of p-Aktser473) in liver and skeletal muscle tissues was determined by Western blotting. Results Serum TG in hypertriglyceridemia group was significantly higher than those in control group and hypercholesterolemia group (P<0.05), and serum TC in hypercholesterolemia group was significantly higher than those in control group and hypertriglyceridemia group (P<0.05). Blood glucose, fasting insulin and HOMA-IR were higher, and ISI was lower in hypertriglyceridemia group than in control group, while there was no significant difference in these parameters between two groups (P>0.05). Blood glucose, fasting insulin and HOMA-IR were significantly higher, and ISI was significantly lower in hypercholesterolemia group than in control group and hypertriglyceridemia group (P<0.05). The relative expression of p-Aktser473 and times of increase in relative expression in liver and skeletal muscle tissues after insulin stimulation in hypertriglyceridemia group and hypercholesterolemia group were significantly lower than those in control group (P<0.05). The increase in relative expression of p-Aktser473 in liver tissues in hypercholesterolemia group was significantly lower than that in hypertriglyceridemia group (P<0.05), and the relative expression of p-Aktser473 in skeletal muscle tissues after insulin stimulation in hypercholesterolemia group was significantly higher than that in hypertriglyceridemia group (P<0.05). Conclusion Mice with hypertriglyceridemia or hypercholesteremia have impaired tissue-targeted insulin sensitivity, and those with hypercholesteremia fed with high-fat diet have more significantly impaired glucose metabolism.

Key words: hyperlipidemia, hypertriglyceridemia, hypercholesteremia, insulin sensitivity, diabetes