An integrative systems genetic analysis of mammalian lipid metabolism

Nature
Benjamin L ParkerBrian G Drew

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.

References

Mar 7, 2003·Genome Biology·Bobby-Joe BreitkreutzMike Tyers
May 1, 2004·BMC Genetics·Jeremy L PeirceRobert W Williams
Oct 30, 2004·Nature Genetics·Gary A ChurchillUNKNOWN Complex Trait Consortium
May 23, 2007·Journal of Cellular Physiology·C Gragnoli, J Cronsell
Oct 24, 2007·Nature Methods·Lukas KällMichael J MacCoss
Oct 30, 2007·Nucleic Acids Research·Andreas RueppH Werner Mewes
Jan 10, 2009·Nature Protocols·Da Wei HuangRichard A Lempicki
Feb 6, 2009·Bioinformatics·Lukas KällWilliam Stafford Noble
Jun 23, 2009·Genome Research·Martin KrzywinskiMarco A Marra
Oct 31, 2009·Journal of Cellular Physiology·Claudia Gragnoli
Nov 4, 2009·Nucleic Acids Research·Andreas RueppH-Werner Mewes
Jun 19, 2010·Journal of Lipid Research·Paul P Van Veldhoven
Jun 23, 2011·PLoS Genetics·Anatole GhazalpourAldons J Lusis
Feb 10, 2012·Nature·Trudy F C MackayRichard A Gibbs
Mar 16, 2012·Bioinformatics·Pierre MillardJean-Charles Portais
Jul 25, 2012·Clinics in Liver Disease·Silvia Sookoian, Carlos J Pirola
Aug 16, 2012·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Gary A ChurchillKaren L Svenson
Nov 1, 1994·Journal of the American Society for Mass Spectrometry·J K EngJ R Yates
Jul 18, 2014·PLoS Genetics·Ville-Petteri MäkinenThemistocles L Assimes
Feb 5, 2015·Cell Metabolism·Thomas Q de Aguiar VallimPeter A Edwards
Feb 5, 2015·Cell Metabolism·Brian W ParksAldons J Lusis
Jun 20, 2015·Metabolites·Zahir H AlshehryPeter J Meikle
Nov 28, 2015·Biochimica Et Biophysica Acta·Hans R WaterhamRonald J A Wanders
Dec 29, 2015·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Zobair M YounossiMark Wymer
Jun 11, 2016·Science·Evan G WilliamsJohan Auwerx
Nov 4, 2016·Nature Reviews. Endocrinology·Peter J Meikle, Scott A Summers
Nov 5, 2016·Journal of Lipid Research·Frode NorheimAldons J Lusis
Dec 17, 2016·Nucleic Acids Research·Andrew Chatr-AryamontriMike Tyers
Mar 9, 2017·Clinical and Molecular Hepatology·Silvia Sookoian, Carlos J Pirola
May 13, 2017·Science·Peter J ThulEmma Lundberg

❮ Previous
Next ❯

Citations

Jul 28, 2019·American Journal of Physiology. Heart and Circulatory Physiology·Kate L WeeksJulie R McMullen
Aug 14, 2019·The Journal of Clinical Investigation·Ji-Yeon ShinHoward J Worman
May 18, 2019·Endocrine Reviews·Matthew J WattMagdalene K Montgomery
Jan 26, 2020·Journal of Clinical Medicine·Jessica L H WaltersElizabeth G Bromfield
Feb 16, 2020·Biological Chemistry·Alexander Bartelt, Scott B Widenmaier
Jun 20, 2020·The Journal of Clinical Endocrinology and Metabolism·Matthew D Lynes, Yu-Hua Tseng
Aug 17, 2020·ELife·Chaitanya A KulkarniPaul S Brookes
Apr 20, 2019·Lab Animal·J Bernadette Moore, James L Thorne
Apr 28, 2019·Biophysics Reviews·David A Stroud
Dec 20, 2019·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Louis GauthierStephen W Michnick
Jan 18, 2020·Nature Communications·Catherine G VasilopoulouFlorian Meier
Dec 6, 2019·Nature·Michael Roden, Gerald I Shulman
Apr 8, 2020·Nature Metabolism·Marcus SeldinAldons J Lusis
Apr 14, 2019·Nature Reviews. Endocrinology·Joel T Haas, Bart Staels
Sep 4, 2019·Nature Biotechnology·Tomasz WilmanskiNathan D Price
Feb 6, 2020·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Inês Cebola
Aug 26, 2020·Metabolites·Alec Millner, G Ekin Atilla-Gokcumen
Sep 23, 2020·Nature Metabolism·Vanessa LinkeJoshua J Coon
Dec 3, 2020·Experimental & Molecular Medicine·Yu WangMinjie Wei
Jan 9, 2021·Molecular Systems Biology·Frode NorheimMarcus M Seldin
Aug 20, 2019·Journal of Molecular Biology·Joan Bestard-EscalasGwendolyn Barceló-Coblijn
Dec 29, 2020·Journal of Lipid Research·Montgomery BlencoweXia Yang
Jan 22, 2021·Cell Systems·Jeffrey Molendijk, Benjamin L Parker
Feb 10, 2021·Journal of Lipid Research·Montgomery BlencoweXia Yang
May 1, 2021·Life·Jayan D M Senevirathna, Shuichi Asakawa
May 13, 2021·Nucleic Acids Research·Jeffrey MolendijkBenjamin L Parker
Jul 17, 2021·Cell Metabolism·Bethan L CliffordThomas Q de Aguiar Vallim
Jul 3, 2021·Cell·Michael A SkinniderLeonard J Foster
Jul 8, 2021·Pharmaceutical Patent Analyst·Hermann Am Mucke
Jul 17, 2021·Molecular Metabolism·Valentina S KlausDominik Lutter
Oct 1, 2021·Scientific Reports·Michał A SurmaChristian Klose
Dec 5, 2021·Scientific Data·Alyssa ImbertEtienne A Thévenot

❮ Previous
Next ❯

Methods Mentioned

BETA
confocal microscopy
antisense oligonucleotides
Assay
PCR

Software Mentioned

Cytoscape
Proteome Discoverer
NIS
Mass Hunter
Andromeda
Protein Validator
MassHunter Quantitative Analysis Program
fast
Qubit
Mascot

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine
Michio Shimabukuro
Nihon rinsho. Japanese journal of clinical medicine
Ken Ebihara, Kazuwa Nakao
Frontiers in Genetics
Huiping Zhou, Runping Liu
© 2022 Meta ULC. All rights reserved