PXD062388

PXD062388 is an original dataset announced via ProteomeXchange.

Title	Hepatic AKAP1 Deficiency Exacerbates Diet-Induced MASLD by Enhancing GPAT1-mediated Lysophosphatidic Acid Synthesis
Description	Metabolic dysfunction-associated steatotic liver disease (MASLD), closely associated with obesity, can progress to metabolic dysfunction-associated steatohepatitis when the liver undergoes overt inflammatory damage. A-kinase anchoring protein 1 (AKAP1) has been shown to control lipid accumulation in brown adipocytes. However, the role of AKAP1 signaling in hepatic lipid metabolism and MASLD remains poorly understood. Here, we showed that hepatocyte-specific AKAP1 deficiency exacerbated hepatic steatosis and steatohepatitis in male mice subjected to a high-fat diet and fast-food diet, respectively. Mechanistically, AKAP1 directly phosphorylated and inactivated glycerol-3-phosphate acyltransferase 1 (GPAT1) in a PKA-dependent manner, thus suppressing lysophosphatidic acid (LPA) production. Increased endogenous LPA in hepatocytes promoted hepatocellular triglyceride (TG) synthesis and initiated pronounced inflammatory response in Kupffer cells. Restoring hepatic AKAP1 or repressing LPA levels via GPAT1 knockdown alleviated MASLD exacerbation. Overall, AKAP1 plays a protective role against MASLD by inhibiting GPAT1 activity, highlighting the potential of targeting AKAP1/PKA/GPAT1 signalosome for MASLD therapy.
HostingRepository	PRIDE
AnnounceDate	2025-05-26
AnnouncementXML	Submission_2025-05-25_16:07:05.707.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Linjie He
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2025-03-30 22:18:08	ID requested
⏵ 1	2025-05-25 16:07:06	announced

He L, She X, Guo L, Gao M, Wang S, Lu Z, Guo H, Li R, Nie Y, Xing J, Ji L, Hepatic AKAP1 deficiency exacerbates diet-induced MASLD by enhancing GPAT1-mediated lysophosphatidic acid synthesis. Nat Commun, 16(1):4286(2025) [pubmed]

10.1038/s41467-025-58790-7;

submitter keyword: AKAP1

MASLD

Lysophosphatidic Acid

GPAT1

triglyceride synthesis.

linjie He
contact affiliation	No. 169 West Changle Road, Xi’an, Shaanxi, 710032, China.
contact email	1186781956@qq.com
lab head
Linjie He
contact affiliation	Fourth Military Medical University
contact email	1186781956@qq.com
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/2025/05/PXD062388

PRIDE project URI

• PRIDE
  1. PXD062388
     1. Label: PRIDE project
     2. Name: Hepatic AKAP1 Deficiency Exacerbates Diet-Induced MASLD by Enhancing GPAT1-mediated Lysophosphatidic Acid Synthesis