Trib1 is a lipid- and myocardial infarction-associated gene that regulates hepatic lipogenesis and VLDL production in mice

被引：122

作者：

Burkhardt, Ralph ^{[1
]}

Toh, Sue-Anne ^{[2
,3
,4
]}

Lagor, William R. ^{[2
]}

Birkeland, Andrew ^{[1
]}

Levin, Michael ^{[2
]}

Li, Xiaoyu ^{[2
]}

Robblee, Megan ^{[1
]}

Fedorov, Victor D. ^{[1
]}

Yamamoto, Masahiro ^{[5
]}

Satoh, Takashi ^{[5
]}

Akira, Shizuo ^{[5
]}

Kathiresan, Sekar ^{[6
,7
,8
,9
]}

Breslow, Jan L. ^{[1
]}

Rader, Daniel J. ^{[2
,3
,10
]}

机构：

[1] Rockefeller Univ, Biochem Genet & Metab Lab, New York, NY 10065 USA

[2] Univ Penn, Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA

[3] Univ Penn, Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA

[4] Univ Penn, Sch Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA

[5] Osaka Univ, WPI Immunol Frontier Res Ctr, Osaka, Japan

[6] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA

[7] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA

[8] Harvard Univ, Sch Med, Boston, MA USA

[9] Broad Inst, Cambridge, MA USA

[10] Univ Penn, Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2010年 / 120卷 / 12期

关键词：

LOCI; TRIGLYCERIDE; CHOLESTEROL; GLUCOSE; ALPHA; RISK;

D O I：

10.1172/JCI44213

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Recent genome-wide association studies have identified a genetic locus at human chromosome 8q24 as having minor alleles associated with lower levels of plasma triglyceride (TG) and LDL cholesterol (LDL-C), higher levels of HDL-C, as well as decreased risk for myocardial infarction. This locus contains only one annotated gene, tribbles homolog 1 (TRIB1), which has not previously been implicated in lipoprotein metabolism. Here we demonstrate a role for Trib1 as a regulator of lipoprotein metabolism in mice. Hepatic-specific overexpression of Trib1 reduced levels of plasma TG and cholesterol by reducing VLDL production; conversely, Trib1-knockout mice showed elevated levels of plasma TG and cholesterol due to increased VLDL production. Hepatic Trib1 expression was inversely associated with the expression of key lipogenic genes and measures of lipogenesis. Thus, we provide functional evidence for what we believe to be a novel gene regulating hepatic lipogenesis and VLDL production in mice that influences plasma lipids and risk for myocardial infarction in humans.

引用

页码：4410 / 4414

页数：5

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