Abstract:

Objective To investigate the glucolipid metabolism and endoplasmic reticulum stress in adipose tissues in lipoprotein lipase (LPL) gene knockout mice. Methods LPL gene knockout heterozygotic mice (LPL+/- group, n=8) and wild-type (WT) C57 mice (control group, n=8) were selected, and each group was subdivided into 16-week-old group(n=4) and 50-week-old group (n=4). Serum levels of triglyceride (TG) and free fatty acid (FFA) were measured, changes of plasma glucose were monitored by intraperitoneal glucose tolerance test (IPGTT), area under the curve of glucose (AUCg) and homeostasis model insulin resistance index (HOMA-IR) were calculated to evaluate insulin sensitivity and β-cell function, and the expression of endoplasmic reticulum stress-related markers (Bip, ATF4, ATF6 and CHOP) in subcutaneous adipose tissues and visceral adipose tissues was detected by Real-Time PCR. Results The serum levels of TG and FFA were significantly higher, and the serum level of FFA was significantly higher in 50-week-old LPL+/- group than those in 16-week-old LPL+/- group (P<0.05). It was revealed by IPGTT that 30 min and 60 min plasma glucose in IPGTT and AUCg in 50-week-old LPL+/- group were significantly higher than those in 50-week-old control group (P<0.05), and 15 min to 120 min plasma glucose in IPGTT and AUCg in 50-week-old LPL+/- group were significantly higher than those in 16-week-old LPL+/- group (P<0.05). HOMA-IR in 50-week-old LPL+/- group was significantly higher than that in 16-week-old LPL+/- group (P<0.05). The expression of Bip, ATF6, ATF4 and CHOP mRNA in subcutaneous adipose tissues in 50-week-old LPL+/- group was significantly higher than that in 50-week-old control group (P<0.05), and was significantly higher than that in 16-week-old LPL+/- group (P<0.05). Conclusion There exist significant dyslipidemia, increased plasma glucose and insulin resistance in LPL+/- mice. The activation of endoplasmic reticulum stress in subcutaneous adipose tissues may be related to insulin resistance in LPL+/- mice with hyperlipidemia.

Key words: lipoprotein lipase, glucolipid metabolism, insulin resistance, endoplasmic reticulum stress