PXD043087-2

PXD043087 is an original dataset announced via ProteomeXchange.

Title	ANGPTL4 binds to leptin receptor to regulate ectopic bone formation and fat metabolism
Description	Leptin protein was thought to be unique to leptin receptor (LepR), but the phenotypes of mice with mutation in LepR (db/db) and leptin (ob/ob) are not identical, and the cause remains unclear. Here, we show that db/db, but not ob/ob mice had defect in tenotomy-induced heterotopic ossification (HO), implicating alternative ligand(s) for LepR might be involved. Ligand screening revealed that ANGPTL4, a stress and fasting-induced factor, was elicited from brown adipose tissue after tenotomy, bound to LepR on PRRX1+ mesenchymal cells at the HO cite, thus promotes chondrogenesis and HO development. Disruption of LepR in PRRX1+ cells, or lineage ablation of LepR+ cells, or deletion of ANGPTL4 impeded chondrogenesis and HO in mice. Surprisingly, exogenous ANGPTL4 treatment not only promoted HO, but facilitated the transformation from white to brown adipose tissue in mice. These findings identify ANGPTL4 as a novel ligand for LepR to stimulate HO and regulate fat metabolism.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:48:22.193.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	WF shao
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-19 01:01:11	ID requested
1	2024-07-03 01:59:19	announced
⏵ 2	2024-10-22 06:48:23	announced	2024-10-22: Updated project metadata.

Hu H, Luo S, Lai P, Lai M, Mao L, Zhang S, Jiang Y, Wen J, Zhou W, Liu X, Wang L, Huang M, Hu Y, Zhao X, Xia L, Zhou W, Jiang Y, Zou Z, Liu A, Guo B, Bai X, ANGPTL4 binds to the leptin receptor to regulate ectopic bone formation. Proc Natl Acad Sci U S A, 121(1):e2310685120(2024) [pubmed]

10.1073/pnas.2310685120;

submitter keyword: leptin receptor

ANGPTL4

heterotopic ossification

fat metabolism

Hongling Hu
contact affiliation	Guangdong Provincial Key Laboratory of Bone and Joint Degenerative Diseases, The Third Affiliated Hospital of Southern Medical University, Guangzhou
contact email	huhongling@smu.edu.cn
lab head
WF shao
contact affiliation	southern medical university
contact email	wf_shao@outlook.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD043087
     1. Label: PRIDE project
     2. Name: ANGPTL4 binds to leptin receptor to regulate ectopic bone formation and fat metabolism