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

Jha, Pooja; McDevitt, Molly T; Halilbasic, Emina; Williams, Evan G; Quiros, Pedro M; Gariani, Karim; Sleiman, Maroun B; Gupta, Rahul; Ulbrich, Arne; Jochem, Adam; Coon, Joshua J; Trauner, Michael; Pagliarini, David J; Auwerx, Johan

doi:10.1016/j.cels.2018.05.009

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Title		Genetic regulation of plasma lipid species and their association with metabolic phenotypes
Authors		Jha, Pooja McDevitt, Molly T Halilbasic, Emina Williams, Evan G Quiros, Pedro M Gariani, Karim Sleiman, Maroun B Gupta, Rahul Ulbrich, Arne Jochem, Adam Coon, Joshua J Trauner, Michael Pagliarini, David J Auwerx, Johan show all authors [1 - 14]
Published in		Cell Systems. 2018, vol. 6, no. 6, p. 709-721.e6
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
Identifiers		DOI: 10.1016/j.cels.2018.05.009 PMID: 29909275
Full text		Article (Published version) (6 MB) - Free access Other version: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6397773/
Structures		Faculté de médecine / Section de médecine clinique / Département de médecine
Research group		Laboratoire de recherche NAFLD et résistance à l'insuline (997)
Project		Swiss National Science Foundation: 31003A_140780
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 https://archive-ouverte.unige.ch/unige:143017