Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 120, Issue 12, Pages 4410-4414Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI44213
Keywords
-
Categories
Funding
- National Heart, Lung and Blood Institute
- NIH [P01-HL059407, RC2-HL101864]
- Bristol-Myers Squibb
- Duetsche Forschungsgemeinschaft [BU2263/1-1]
- NIH MSTP [GM07739]
- American Heart Association [0315294T]
- Institute for Translational Medicine and Therapeutics, University of Pennsylvania
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available