Year: 2018
Type: article
Abstract: The genetic regulation and physiological impact of most lipid species are unexplored. Here, we profiled 129 plasma lipid species across 49 strains of the BXD mouse genetic reference population fed either chow or a high-fat diet. By integrating these data with genomics and phenomics datasets, we elucidated genes by environment (diet) interactions that regulate systemic metabolism. We found quantitative trait loci (QTLs) for ∼94% of the lipids measured. Several QTLs harbored genes associated with blood lipid levels and abnormal lipid metabolism in human genome-wide association studies. Lipid species from different classes provided signatures of metabolic health, including seven plasma triglyceride species that associated with either healthy or fatty liver. This observation was further validated in an independent mouse model of non-alcoholic fatty liver disease (NAFLD) and in plasma from NAFLD patients. This work provides a resource to identify plausible genes regulating the measured lipid species and their association with metabolic traits.
Source: Cell Systems
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $9,350
Funders: National Science Foundation, École Polytechnique Fédérale de Lausanne, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Austrian Science Fund, SystemsX.ch, National Institutes of Health, National Institute on Aging, National Institute of General Medical Sciences
Awards: G2057039631, G2232381808, Transcriptional cofactor networks and metabolism, Systematic functional annotation of the mitochondrial proteome, Structure, Function and Regulation of the Proteome, G3418984644, G346233577, Translational Systems Genetics of Mitochondria, Metabolism, and Aging, G5981877352, Graduate Training in Molecular Biosciences, G7502741305, G9000007040, G9000068044, G9000093729
OpenAlex ID: W2808430950