PXD005128

PXD005128 is an original dataset announced via ProteomeXchange.

Title	Proteomic analysis of adipocyte insulin resistance
Description	Insulin resistance is a major risk factor for human metabolic diseases including type 2 diabetes, cardiovascular diseases and some cancers. We analysed the proteome analyses across in vitro and in vivo models of insulin resistance to find common features of insulin resistance and identified lower expression of enzymes within the mevalonate pathway. mitochondrial CoQ was lower in all models of insulin resistance. Specifically, the coenzyme Q (CoQ) biosynthetic proteins Coq 7 and 9 were decreased in adipose tissue from a mouse model of diet-induced obesity, and mitochondrial CoQ was lower in all models of insulin resistance. Moreover, the mitochondrial content of CoQ in adipose tissue correlated positively with insulin sensitivity in obese humans. Inhibition of CoQ biosynthesis induced insulin resistance, while replenishment of CoQ restored insulin sensitivity in cell culture models and in animals, demonstrating that loss of CoQ is both necessary and sufficient for adipocyte insulin resistance. Mechanistically, loss of CoQ increased mitochondrial peroxides. These findings place defective mitochondrial CoQ homeostasis upstream of increased mitochondrial oxidants in the induction of insulin resistance in adipocytes and highlight the CoQ biosynthetic pathway as an appealing therapeutic target to combat insulin resistance.
HostingRepository	PRIDE
AnnounceDate	2018-02-07
AnnouncementXML	Submission_2018-02-07_06:02:36.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Daniel Fazakerley
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	carbamoylated residue; monohydroxylated residue
Instrument	Q Exactive; LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2016-10-11 01:13:35	ID requested
⏵ 1	2018-02-07 06:02:36	announced

Dataset with its publication pending

curator keyword: Biomedical

submitter keyword: Mouse, adipocyte, adipose tissue, insulin resistance, LC-MS/MS, Orbitrap

David James
contact affiliation	Charles Perkins Centre, School of Life and Environmental Sciences and Sydney Medical School, University of Sydney, Camperdown, NSW, Australia
contact email	david.james@sydney.edu.au
lab head
Daniel Fazakerley
contact affiliation	University of Sydney
contact email	daniel.fazakerley@sydney.edu.au
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/02/PXD005128

PRIDE project URI

• PRIDE
  1. PXD005128
     1. Label: PRIDE project
     2. Name: Proteomic analysis of adipocyte insulin resistance