上海交通大学学报（医学版）

›› 2011, Vol. 31 ›› Issue (4): 401-.doi: 10.3969/j.issn.1674-8115.2011.04.004

• 论著（基础研究） • 上一篇    下一篇

脂蛋白脂肪酶基因敲除小鼠糖脂代谢与脂肪组织内质网应激研究

金 晶, 胡耀敏, 李圣贤, 刘 伟   

  1. 上海交通大学 |医学院附属仁济医院内分泌科, 上海 200127
  • 出版日期:2011-04-28 发布日期:2011-04-28
  • 通讯作者: 胡耀敏, 电子信箱: amin99@163.com。
  • 作者简介:金 晶（1983—）, 女, 硕士生；电子信箱: dingdong-jing@163.com。
  • 基金资助:

    国家自然科学基金（30670988）；浦东新区社会发展局卫生科技项目（PW2008D-1）

Glucolipid metabolism and endoplasmic reticulum stress in adipose tissues in lipoprotein lipase gene knockout mice

JIN Jing, HU Yao-min, LI Sheng-xian, LIU Wei   

  1. Department of Endocrinology and Metabolic Diseases, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200127, China
  • Online:2011-04-28 Published:2011-04-28
  • Supported by:

    National Natural Science Foundation of China, 30670988；Shanghai Pudong New Area Social Development Bureau Foundation, PW2008D-1

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摘要：

目的 研究脂蛋白脂肪酶(LPL）基因敲除小鼠糖脂代谢特点及脂肪组织内质网应激情况。方法 以LPL基因敲除杂合子小鼠（LPL+/-组，n=8）和野生型（WT）C57小鼠（对照组，n=8）作为实验对象，两组再分为16周龄组（n=4）和50周龄组（n=4）。测定血清三酰甘油（TG）和游离脂肪酸（FFA）水平；腹腔注射葡萄糖耐量试验（IPGTT）监测血糖变化，计算葡萄糖曲线下面积(AUCg)和稳态模型胰岛素抵抗指数（HOMA-IR）,评价胰岛素敏感性及胰岛β细胞功能；采用Real-Time PCR技术检测皮下脂肪和内脏脂肪组织中内质网应激相关因子（Bip、ATF4、ATF6和CHOP）的表达。结果 50周龄LPL+/-组小鼠血清TG和FFA水平均显著高于50周龄对照组小鼠，血清FFA水平明显高于16周龄LPL+/-组小鼠（P<0.05）。IPGTT结果显示：50周龄LPL+/-组小鼠IPGTT 30、60 min血糖及AUCg均显著高于50周龄对照组（P<0.05），且IPGTT 15~120 min血糖和AUCg 均显著高于16周龄LPL+/-组（P<0.05）。与16周龄LPL+/-组比较，50周龄LPL+/-组小鼠HOMA-IR显著升高（P<0.05）。50周龄LPL+/-组小鼠皮下脂肪组织中Bip、ATF6、ATF4和CHOP mRNA表达均显著高于50周龄对照组（P<0.05），且明显高于16周龄LPL+/-组（P<0.05）。结论 LPL+/-小鼠脂代谢紊乱明显，血糖升高且存在胰岛素抵抗，皮下脂肪组织可能通过内质网应激参与高脂血症LPL+/-小鼠胰岛素抵抗的发生。

关键词: 脂蛋白脂肪酶, 脂代谢, 胰岛素抵抗, 内质网应激

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