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

Ralph Burkhardt, Sue Anne Toh, William R. Lagor, Andrew Birkeland, Michael Levin, Xiaoyu Li, Megan Robblee, Victor D. Fedorov, Masahiro Yamamoto, Takashi Satoh, Shizuo Akira, Sekar Kathiresan, Jan L. Breslow, Daniel J. Rader

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)4410-4414
Number of pages5
JournalJournal of Clinical Investigation
Volume120
Issue number12
DOIs
StatePublished - Dec 1 2010
Externally publishedYes

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Lipogenesis
Myocardial Infarction
Lipids
Triglycerides
Liver
Genes
Lipoproteins
VLDL Cholesterol
Genetic Loci
Genome-Wide Association Study
Human Chromosomes
Knockout Mice
LDL Cholesterol
Alleles
Cholesterol

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Trib1 is a lipid- and myocardial infarction-associated gene that regulates hepatic lipogenesis and VLDL production in mice. / Burkhardt, Ralph; Toh, Sue Anne; Lagor, William R.; Birkeland, Andrew; Levin, Michael; Li, Xiaoyu; Robblee, Megan; Fedorov, Victor D.; Yamamoto, Masahiro; Satoh, Takashi; Akira, Shizuo; Kathiresan, Sekar; Breslow, Jan L.; Rader, Daniel J.

In: Journal of Clinical Investigation, Vol. 120, No. 12, 01.12.2010, p. 4410-4414.

Research output: Contribution to journalArticle

Burkhardt, R, Toh, SA, Lagor, WR, Birkeland, A, Levin, M, Li, X, Robblee, M, Fedorov, VD, Yamamoto, M, Satoh, T, Akira, S, Kathiresan, S, Breslow, JL & Rader, DJ 2010, 'Trib1 is a lipid- and myocardial infarction-associated gene that regulates hepatic lipogenesis and VLDL production in mice', Journal of Clinical Investigation, vol. 120, no. 12, pp. 4410-4414. https://doi.org/10.1172/JCI44213
Burkhardt, Ralph ; Toh, Sue Anne ; Lagor, William R. ; Birkeland, Andrew ; Levin, Michael ; Li, Xiaoyu ; Robblee, Megan ; Fedorov, Victor D. ; Yamamoto, Masahiro ; Satoh, Takashi ; Akira, Shizuo ; Kathiresan, Sekar ; Breslow, Jan L. ; Rader, Daniel J. / Trib1 is a lipid- and myocardial infarction-associated gene that regulates hepatic lipogenesis and VLDL production in mice. In: Journal of Clinical Investigation. 2010 ; Vol. 120, No. 12. pp. 4410-4414.
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