@article{340a647c3b494f30be55207a8daf00d8,
title = "An integrative systems genetic analysis of mammalian lipid metabolism",
abstract = "Dysregulation of lipid homeostasis is a precipitating event in the pathogenesis and progression of hepatosteatosis and metabolic syndrome. These conditions are highly prevalent in developed societies and currently have limited options for diagnostic and therapeutic intervention. Here, using a proteomic and lipidomic-wide systems genetic approach, we interrogated lipid regulatory networks in 107 genetically distinct mouse strains to reveal key insights into the control and network structure of mammalian lipid metabolism. These include the identification of plasma lipid signatures that predict pathological lipid abundance in the liver of mice and humans, defining subcellular localization and functionality of lipid-related proteins, and revealing functional protein and genetic variants that are predicted to modulate lipid abundance. Trans-omic analyses using these datasets facilitated the identification and validation of PSMD9 as a previously unknown lipid regulatory protein. Collectively, our study serves as a rich resource for probing mammalian lipid metabolism and provides opportunities for the discovery of therapeutic agents and biomarkers in the setting of hepatic lipotoxicity.",
author = "Parker, {Benjamin L.} and Calkin, {Anna C.} and Seldin, {Marcus M.} and Keating, {Michael F.} and Tarling, {Elizabeth J.} and Pengyi Yang and Moody, {Sarah C.} and Yingying Liu and Zerenturk, {Eser J.} and Needham, {Elise J.} and Miller, {Matthew L.} and Clifford, {Bethan L.} and Pauline Morand and Watt, {Matthew J.} and Meex, {Ruth C.R.} and Peng, {Kang Yu} and Richard Lee and Kaushala Jayawardana and Calvin Pan and Mellett, {Natalie A.} and Weir, {Jacquelyn M.} and Ross Lazarus and Lusis, {Aldons J.} and Meikle, {Peter J.} and James, {David E.} and {de Aguiar Vallim}, {Thomas Q.} and Drew, {Brian G.}",
note = "Funding Information: Acknowledgements This work was supported in part by the following: ANZ Victorian Medical Research Trust, Baker Heine Trust, Victorian State Government{\textquoteright}s OIS Program and National Heart Foundation of Australia (A.C.C., B.G.D. and E.J.Z.); National Health and Medical Research Council of Australia (NHMRC) grants and fellowships (D.E.J. and B.L.P.); NIH grants HL122677, DK112119, DK102559 (T.Q.d.A.V.), HL028481 (A.J.L., T.Q.d.A.V.), HL118161 and HL136543 (E.J.T.); American Heart Association grant SDG18440015 (T.Q.d.A.V.). Baker Bright Sparks Scholarship and Australian Post-graduate Award (M.F.K.). We thank B. Crossett, S. Cordwell and The Sydney University Mass Spectrometry Facility. We are also grateful for the help and guidance of I. Carmichael and S. Bond and our many internal and external collaborators. Publisher Copyright: {\textcopyright} 2019, The Author(s), under exclusive licence to Springer Nature Limited.",
year = "2019",
month = mar,
day = "14",
doi = "10.1038/s41586-019-0984-y",
language = "English",
volume = "567",
pages = "187--193",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7747",
}