en
Scientific article
Open access
English

Genetic regulation of plasma lipid species and their association with metabolic phenotypes

Published inCell Systems, vol. 6, no. 6, p. 709-721.e6
Publication date2018
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.

Keywords
  • Adult
  • Animals
  • Cohort Studies
  • Diet
  • High-Fat
  • Disease Models
  • Animal
  • Female
  • Gene Expression Regulation/genetics
  • Genome-Wide Association Study
  • Humans
  • Lipid Metabolism/genetics/physiology
  • Lipids/blood/genetics/physiology
  • Liver/metabolism
  • Male
  • Mice
  • Mice
  • Inbred C57BL
  • Mice
  • Inbred DBA
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease/genetics
  • Prospective Studies
  • Quantitative Trait Loci
  • Triglycerides/metabolism
Citation (ISO format)
JHA, Pooja et al. Genetic regulation of plasma lipid species and their association with metabolic phenotypes. In: Cell Systems, 2018, vol. 6, n° 6, p. 709–721.e6. doi: 10.1016/j.cels.2018.05.009
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Article (Published version)
Identifiers
ISSN of the journal2405-4720
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124downloads

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