Journal article

An integrative systems genetic analysis of mammalian lipid metabolism

Benjamin L Parker, Anna C Calkin, Marcus M Seldin, Michael F Keating, Elizabeth J Tarling, Pengyi Yang, Sarah C Moody, Yingying Liu, Eser J Zerenturk, Elise J Needham, Matthew L Miller, Bethan L Clifford, Pauline Morand, Matthew J Watt, Ruth CR Meex, Kang-Yu Peng, Richard Lee, Kaushala Jayawardana, Calvin Pan, Natalie A Mellett Show all

NATURE | NATURE PUBLISHING GROUP | Published : 2019

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 f..

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Grants

Awarded by NIH


Awarded by American Heart Association


Awarded by NATIONAL HEART, LUNG, AND BLOOD INSTITUTE


Awarded by NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES


Funding Acknowledgements

This work was supported in part by the following: ANZ Victorian Medical Research Trust, Baker Heine Trust, Victorian State Government'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.