The genetic architecture of NAFLD among inbred strains of mice
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Author
Hui, Simon T
Parks, Brian W
Org, Elin
Norheim, Frode
Che, Nam
Pan, Calvin
Castellani, Lawrence W
Charugundla, Sarada
Dirks, Darwin L
Psychogios, Nikolaos
Neuhaus, Isaac
Kirchgessner, Todd
Gargalovic, Peter S
Lusis, Aldons J
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.7554/eLife.05607Metadata
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Hui, S. T., B. W. Parks, E. Org, F. Norheim, N. Che, C. Pan, L. W. Castellani, et al. 2015. “The genetic architecture of NAFLD among inbred strains of mice.” eLife 4 (1): e05607. doi:10.7554/eLife.05607. http://dx.doi.org/10.7554/eLife.05607.Abstract
To identify genetic and environmental factors contributing to the pathogenesis of non-alcoholic fatty liver disease, we examined liver steatosis and related clinical and molecular traits in more than 100 unique inbred mouse strains, which were fed a diet rich in fat and carbohydrates. A >30-fold variation in hepatic TG accumulation was observed among the strains. Genome-wide association studies revealed three loci associated with hepatic TG accumulation. Utilizing transcriptomic data from the liver and adipose tissue, we identified several high-confidence candidate genes for hepatic steatosis, including Gde1, a glycerophosphodiester phosphodiesterase not previously implicated in triglyceride metabolism. We confirmed the role of Gde1 by in vivo hepatic over-expression and shRNA knockdown studies. We hypothesize that Gde1 expression increases TG production by contributing to the production of glycerol-3-phosphate. Our multi-level data, including transcript levels, metabolite levels, and gut microbiota composition, provide a framework for understanding genetic and environmental interactions underlying hepatic steatosis. DOI: http://dx.doi.org/10.7554/eLife.05607.001Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4493743/pdf/Terms of Use
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