Reference : Systems Analyses Reveal Physiological Roles and Genetic Regulators of Liver Lipid Species.
Scientific journals : Article
Life sciences : Genetics & genetic processes
http://hdl.handle.net/10993/43144
Systems Analyses Reveal Physiological Roles and Genetic Regulators of Liver Lipid Species.
English
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. [> >]
2018
Cell systems
6
6
722-733.e6
Yes (verified by ORBilu)
2405-4712
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.
http://hdl.handle.net/10993/43144
Copyright (c) 2018 The Authors. Published by Elsevier Inc. All rights reserved.

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