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Systems Analyses Reveal Physiological Roles and Genetic Regulators of Liver Lipid Species.

Pooja Jha | Molly T McDevitt | Rahul Gupta | Pedro M Quiros | Evan G Williams | Karim Gariani | Maroun B Sleiman | Leo Diserens | Adam Jochem | Arne Ulbrich | Joshua J Coon | Johan Auwerx | David J Pagliarini
Cell systems | 2018

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.

Pubmed ID: 29909277

Research resources used in this publication

None found

Antibodies used in this publication

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Associated grants

  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM007215
  • Agency: NIA NIH HHS, United States
    Id: R01 AG043930
  • Agency: NIGMS NIH HHS, United States
    Id: R35 GM118110
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM115591
  • Agency: NIGMS NIH HHS, United States
    Id: P41 GM108538
  • Agency: NIGMS NIH HHS, United States
    Id: F32 GM119190

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