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

Autor:	Jha P; Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland., McDevitt MT; Morgridge Institute for Research, Madison, WI 53715, USA; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA., Gupta R; Morgridge Institute for Research, Madison, WI 53715, USA., Quiros PM; Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland., Williams EG; Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland., Gariani K; Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland., Sleiman MB; Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland., Diserens L; Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland., Jochem A; Morgridge Institute for Research, Madison, WI 53715, USA., Ulbrich A; Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA., Coon JJ; Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA., Auwerx J; Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland. Electronic address: admin.auwerx@epfl.ch., Pagliarini DJ; Morgridge Institute for Research, Madison, WI 53715, USA; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA. Electronic address: dpagliarini@morgridge.org.
Jazyk:	angličtina
Zdroj:	Cell systems [Cell Syst] 2018 Jun 27; Vol. 6 (6), pp. 722-733.e6. Date of Electronic Publication: 2018 Jun 13.
DOI:	10.1016/j.cels.2018.05.016
Abstrakt:	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 © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu