Apolipoprotein C3 deficiency results in diet-induced obesity and aggravated insulin resistance in mice

被引:92
作者
Duivenvoorden, I
Teusink, B
Rensen, PC
Romjjn, JA
Havekes, LM
Voshol, PJ
机构
[1] Leiden Univ, Med Ctr, Dept Endocrinol & Metab Dis, NL-2300 RC Leiden, Netherlands
[2] TNO Prevent & Hlth, Gaubius Lab, Leiden, Netherlands
[3] Leiden Univ, Med Ctr, Dept Gen Internal Med, Leiden, Netherlands
[4] Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands
关键词
D O I
10.2337/diabetes.54.3.664
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Our aim was to study whether the absence of apolipoprotein (apo) C3, a strong inhibitor of lipoprotein lipase (LPL), accelerates the development of obesity and consequently insulin resistance. Apoc3(-/-) mice and wild-type littermates were fed a high-fat (46 energy %) diet for 20 weeks. After 20 weeks of high-fat feeding, apoc3(-/-) mice showed decreased plasma triglyceride levels (0.11 +/- 0.02 vs. 0.29 +/- 0.04 mmol, P < 0.05) and were more obese (42.8 +/- 3.2 vs. 35.2 +/- 3.3 g; P < 0.05) compared with wild-type littermates. This increase in body weight was entirely explained by increased body lipid mass (16.2 +/- 5.9 vs. 10.0 +/- 1.8 g; P < 0.05). LPL-dependent uptake of triglyceride-derived fatty acids by adipose tissue was significantly higher in apoc3(-/-) mice. LPL-independent uptake of albuminbound fatty acids did not differ. It is interesting that whole-body insulin sensitivity using hyperinsulinemiceuglycemic clamps was decreased by 43% and that suppression of endogenous glucose production was decreased by 25% in apoc3(-/-) mice compared with control mice. Absence of apoC3, the natural LPL inhibitor, enhances fatty acid uptake from plasma triglycerides in adipose tissue, which leads to higher susceptibility to diet-induced obesity followed by more severe development of insulin resistance. Therefore, apoC3 is a potential target for treatment of obesity and insulin resistance.
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收藏
页码:664 / 671
页数:8
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