PXD039894

PXD039894 is an original dataset announced via ProteomeXchange.

Title	MBOAT7-Driven Lysophosphatidylinositol Acylation in Adipocytes Contributes to Systemic Glucose Homeostasis
Description	We previously demonstrated that antisense oligonucleotide (ASO)-mediated knockdown of Mboat7, the gene encoding Membrane Bound O-Acyltransferase 7, in the liver and adipose tissue of mice promoted high fat diet-induced hepatic steatosis, hyperinsulinemia, and systemic insulin resistance. Thereafter, other groups showed that hepatocyte-specific genetic deletion of Mboat7 promoted striking fatty liver and NAFLD progression in mice but does not alter insulin sensitivity, suggesting the potential for cell autonomous roles. Here, we show that MBOAT7 function in adipocytes contributes to diet-induced metabolic disturbances including hyperinsulinemia and systemic insulin resistance. We generated floxed Mboat7 mice and created hepatocyte- and adipocyte-specific knockout mice using Cre-recombinase mice under the control of the albumin and adiponectin promoter, respectively. After chow and high fat diet feeding (60% kCal fat), mice were subjected to metabolic phenotyping and tissues to molecular workup and analysis. Here, we show that MBOAT7 function in adipocytes contributes to diet-induced metabolic disturbances including hyperinsulinemia and systemic insulin resistance. The expression of Mboat7 in white adipose tissue closely correlates with diet-induced obesity across a panel of ~100 inbred strains of mice fed a high fat/high sucrose diet. Moreover, we found that adipocyte-specific genetic deletion of Mboat7 is sufficient to promote hyperinsulinemia, systemic insulin resistance, and mild fatty liver. Unlike in the liver, where Mboat7 plays a relatively minor role in maintaining arachidonic acid (AA)-containing PI pools, Mboat7 is the major source of AA-containing PI pools in adipose tissue. Our data demonstrate that MBOAT7 is a critical regulator of adipose tissue PI homeostasis, and adipocyte MBOAT7-driven PI biosynthesis is closely linked to hyperinsulinemia and insulin resistance in mice.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:47:44.808.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD039894
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Ling Li
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-02-06 05:57:16	ID requested
1	2023-05-10 14:57:21	announced
⏵ 2	2023-11-14 08:47:57	announced	2023-11-14: Updated project metadata.

10.6019/PXD039894;

Massey WJ, Varadharajan V, Banerjee R, Brown AL, Horak AJ, Hohe RC, Jung BM, Qiu Y, Chan ER, Pan C, Zhang R, Allende DS, Willard B, Cheng F, Lusis AJ, Brown JM, MBOAT7-driven lysophosphatidylinositol acylation in adipocytes contributes to systemic glucose homeostasis. J Lipid Res, 64(4):100349(2023) [pubmed]

submitter keyword: metabolism, hepatocytes, obesity, phosphatidylinositol biosynthesis, systemic insulin resistance, hyperinsulinemia, arachidonic acid, acyltransferase,Non-alcoholic fatty liver disease, diabetes

Mark Brown
contact affiliation	Department of Cardiovascular & Metabolic Sciences, Cleveland Clinic Foundation, USA
contact email	brownm5@ccf.org
lab head
Ling Li
contact affiliation	Cleveland Clinic
contact email	lil5@ccf.org
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/2023/05/PXD039894

PRIDE project URI

• PRIDE
  1. PXD039894
     1. Label: PRIDE project
     2. Name: MBOAT7-Driven Lysophosphatidylinositol Acylation in Adipocytes Contributes to Systemic Glucose Homeostasis