Reference : Systems Analyses Reveal Physiological Roles and Genetic Regulators of Liver Lipid Species.
Scientific journals : Article
Life sciences : Genetics & genetic processes
Systems Analyses Reveal Physiological Roles and Genetic Regulators of Liver Lipid Species.
Jha, Pooja [> >]
McDevitt, Molly T. [> >]
Gupta, Rahul [> >]
Quiros, Pedro M. [> >]
Williams, Evan mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Gariani, Karim [> >]
Sleiman, Maroun B. [> >]
Diserens, Leo [> >]
Jochem, Adam [> >]
Ulbrich, Arne [> >]
Coon, Joshua J. [> >]
Auwerx, Johan [> >]
Pagliarini, David J. [> >]
Cell systems
Yes (verified by ORBilu)
United States
[en] Animals ; Diet, High-Fat ; Female ; Gene Expression Regulation/genetics ; Genome-Wide Association Study/methods ; Lipid Metabolism/physiology ; Lipids/classification/genetics ; Liver/chemistry/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Non-alcoholic Fatty Liver Disease/genetics ; Phenotype ; Quantitative Trait Loci ; Reproducibility of Results ; Systems Analysis ; BXD ; cardiolipin ; fatty liver ; genetic reference population, GRP ; genetic variation ; genome-wide association study, GWAS ; lipid species ; lipidomics ; non-alcoholic fatty liver disease, NAFLD ; quantitative trait locus, QTL
[en] The genetics of individual lipid species and their relevance in disease is largely unresolved. We profiled a subset of storage, signaling, membrane, and mitochondrial liver lipids across 385 mice from 47 strains of the BXD mouse population fed chow or high-fat diet and integrated these data with complementary multi-omics datasets. We identified several lipid species and lipid clusters with specific phenotypic and molecular signatures and, in particular, cardiolipin species with signatures of healthy and fatty liver. Genetic analyses revealed quantitative trait loci for 68% of the lipids (lQTL). By multi-layered omics analyses, we show the reliability of lQTLs to uncover candidate genes that can regulate the levels of lipid species. Additionally, we identified lQTLs that mapped to genes associated with abnormal lipid metabolism in human GWASs. This work provides a foundation and resource for understanding the genetic regulation and physiological significance of lipid species.
Copyright (c) 2018 The Authors. Published by Elsevier Inc. All rights reserved.

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