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Horm Metab Res 2006; 38(8): 491-496
DOI: 10.1055/s-2006-949530
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Catalytically Inactive Lipoprotein Lipase Overexpression Increases Insulin Sensitivity in Mice

M. Shibasaki 1 , H. Bujo 2 , K. Takahashi 1 , K. Murakami 1 , H. Unoki 3 , Y. Saito 1
  • 1Department of Clinical Cell Biology (F5), Graduate School of Medicine, Chiba University, Chiba, Japan
  • 2Department of Genome Research and Clinical Application (M6), Graduate School of Medicine, Chiba University, Chiba, Japan
  • 3Division of Applied Translational Research, Graduate School of Medicine, Chiba University, Chiba, Japan
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Publication History

Received 19 September 2005

Accepted after revision 1 March 2006

Publication Date:
29 August 2006 (online)

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Abstract

Abnormalities in lipoprotein lipase (LPL) function contribute to the development of hypertriglyceridemia, one of the characteristic disorders observed in the metabolic syndrome. In addition to the hydrolyzing activity of triglycerides, LPL modulates various cellular functions via its binding ability to the cell surface. Here we show the effects of catalytically inactive LPL overexpression on high-fat diet (HFD)-induced decreased systemic insulin sensitivity in mice. The binding capacity of catalytically inactive G188E-LPL to C2C12 skeletal muscle cells was not significantly different from that of wild type LPL. Insulin-stimulated IRS-1 phosphorylation and glucose uptake were increased by addition of wild type or mutant LPL in C2C12 cells. After 10 weeks' of HFD feeding, mice had significantly higher blood glucose levels than chow-fed mice in insulin tolerance tests. The blood glucose levels after insulin injection was significantly decreased in mutated LPL-overexpressing mice (G188E mice), as well as in wild type LPL-overexpressing mice (WT mice). Overexpression of catalytically inactive LPL, as well as wild type LPL, improved impaired insulin sensitivity in mice. These results show that decreased expression of LPL possibly causes the insulin resistance, in addition to hypertriglyceridemia, in metabolic syndrome.

Key words

High-fat diet - metabolic syndrome - insulin resistance - cell implantation - skeletal muscle

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Correspondence

H. Bujo

Department of Genome Research and Clinical Application (M6)·Graduate School of Medicine, Chiba University

1-8-1 Inohana·Chuo-ku·Chiba 260-8670·Japan

Phone: +81/43/222 71 71 ext. 52 57

Fax: +81/43/226 20 95

Email: hbujo@faculty.chiba-u.jp