PXD039894 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 | 2023-05-10 |
AnnouncementXML | Submission_2023-05-10_14:57:20.390.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD039894 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | LingLi |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
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. |
Publication List
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] |
Keyword List
submitter keyword: metabolism, hepatocytes, obesity, phosphatidylinositol biosynthesis, systemic insulin resistance, hyperinsulinemia, arachidonic acid, acyltransferase,Non-alcoholic fatty liver disease, diabetes |
Contact List
MarkBrown |
contact affiliation | Department of Cardiovascular & Metabolic Sciences, Cleveland Clinic Foundation, USA |
contact email | brownm5@ccf.org |
lab head | |
LingLi |
contact affiliation | Cleveland Clinic |
contact email | lil5@ccf.org |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD039894
- Label: PRIDE project
- Name: MBOAT7-Driven Lysophosphatidylinositol Acylation in Adipocytes Contributes to Systemic Glucose Homeostasis