| First Author | Hui ST | Year | 2015 |
| Journal | Elife | Volume | 4 |
| Pages | e05607 | PubMed ID | 26067236 |
| Mgi Jnum | J:223755 | Mgi Id | MGI:5660159 |
| Doi | 10.7554/eLife.05607 | Citation | Hui ST, et al. (2015) The genetic architecture of NAFLD among inbred strains of mice. Elife 4:e05607 |
| abstractText | 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. |
