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学科主题基础医学
Overexpression of lipoprotein lipase in transgenic watanabe heritable hyperlipidemic rabbits improves hyperlipidemia and obesity
Koike, T1; Liang, JY1; Wang, XF1; Ichikawa, T1; Shiomi, M1; Liu, G1; Sun, HJ1; Kitajima, S1; Morimoto, M1; Watanabe, T1; Yamada, N1; Fan, JL1
刊名JOURNAL OF BIOLOGICAL CHEMISTRY
2004-02-27
DOI10.1074/jbc.M311514200
279期:9页:7521-7529
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology
研究领域[WOS]Biochemistry & Molecular Biology
关键词[WOS]LOW-DENSITY-LIPOPROTEIN ; CHOLESTEROL-FED RABBITS ; INSULIN-RESISTANCE ; ADIPOSE-TISSUE ; LDL RECEPTOR ; APOLIPOPROTEIN-E ; SKELETAL-MUSCLE ; KNOCKOUT MICE ; ATHEROSCLEROSIS ; METABOLISM
英文摘要

Lipoprotein lipase (LPL) is the rate-limiting enzyme for the hydrolysis of the triglyceride-rich lipoproteins and plays a critical role in lipoprotein and free fatty acid metabolism. Genetic manipulation of LPL may be beneficial in the treatment of hypertriglyceridemias, but it is unknown whether increased LPL activity may be effective in lowering plasma cholesterol and improving insulin resistance in familial hypercholesterolemic patients. To test the hypothesis that stimulation of LPL expression may be used as an adjunctive therapy for treatment of homozygous familial hypercholesterolemia, we have generated transgenic (Tg) Watanabe heritable hyperlipidemic (WHHL) rabbits that overexpress the human LPL transgene and compared their plasma lipid levels, glucose metabolism, and body fat accumulation with those of non-Tg WHHL rabbits. Overexpression of LPL dramatically ameliorated hypertriglyceridemia in Tg WHHL rabbits. Furthermore, increased LPL activity in male Tg WHHL rabbits also corrected hypercholesterolemia (544+/-52 in non-Tg versus 227+/-29 mg/dl in Tg, p<0.01) and reduced body fat accumulation by 61% (323&PLUSMN;27 in non-Tg versus 125&PLUSMN;21 g in Tg, p<0.01), suggesting that LPL plays an important role in mediating plasma cholesterol homeostasis and adipose accumulation. In addition, overexpression of LPL significantly suppressed high fat diet-induced obesity and insulin resistance in Tg WHHL rabbits. These results imply that systemic elevation of LPL expression may be potentially useful for the treatment of hyperlipidemias, obesity, and insulin resistance.

语种英语
WOS记录号WOS:000189103300020
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被引频次:40[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/51715
专题北京大学基础医学院_心血管所
作者单位1.Kobe Univ, Sch Med, Inst Expt Anim, Kobe, Hyogo 6500017, Japan
2.Saga Univ, Sch Med, Saga 8498502, Japan
3.Univ Tsukuba, Inst Basic Med Sci, Dept Pathol, Cardiovasc Dis Lab, Tsukuba, Ibaraki 3058575, Japan
4.Peking Univ, Inst Cardiovasc Sci, Beijing 100083, Peoples R China
5.Dalian Med Univ, Dept Pharmacol, Dalian 116027, Peoples R China
6.Univ Tsukuba, Inst Clin Med, Div Endocrinol & Metab, Tsukuba, Ibaraki 3058575, Japan
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GB/T 7714
Koike, T,Liang, JY,Wang, XF,et al. Overexpression of lipoprotein lipase in transgenic watanabe heritable hyperlipidemic rabbits improves hyperlipidemia and obesity[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2004,279(9):7521-7529.
APA Koike, T.,Liang, JY.,Wang, XF.,Ichikawa, T.,Shiomi, M.,...&Fan, JL.(2004).Overexpression of lipoprotein lipase in transgenic watanabe heritable hyperlipidemic rabbits improves hyperlipidemia and obesity.JOURNAL OF BIOLOGICAL CHEMISTRY,279(9),7521-7529.
MLA Koike, T,et al."Overexpression of lipoprotein lipase in transgenic watanabe heritable hyperlipidemic rabbits improves hyperlipidemia and obesity".JOURNAL OF BIOLOGICAL CHEMISTRY 279.9(2004):7521-7529.
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