PXD017539 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | AIG1 and ADTRP are endogenous FAHFA hydrolases |
Description | Fatty acid esters of hydroxy fatty acids (FAHFAs) are a newly discovered class of signaling lipids with anti-inflammatory and anti-diabetic activities. However, the endogenous regulation of FAHFAs remains a pressing but unanswered question. Here, we find that androgen- induced gene 1 (AIG1) and androgen-dependent TFPI-regulating protein (ADTRP), two threonine hydrolases, control FAHFA levels in vivo. Tissues from mice lacking ADTRP (Adtrp-KO), AIG1 (Aig1-KO), and AIG1/ADTRP (DKO) have higher concentrations of FAHFAs, including 9-PAHSA, due to decreased FAHFA hydrolysis activity. No other lipids were changing in these samples to indicate that AIG1 and ADTRP are specific FAHFA hydrolases. To complement these genetic studies, we identified a dual AIG1/ADTRP inhibitor, ABD-110207, that is active in vivo. Acute treatment of wild-type mice with ABD-110207 results in elevated FAHFA levels further supporting AIG1 and ADTRP enzymatic activity in controlling endogenous FAHFAs. The loss of AIG1/ADTRP does not mimic the effects of pharmacologically administered FAHFAs on glucose tolerance or insulin sensitivity in mice, indicating that therapeutic strategies should continue to focus on FAHFA administration. Together, these studies designate AIG1 and ADTRP as the first endogenous FAHFA hydrolases identified and provide critical genetic and chemical tools for further characterization of these enzymes and endogenous FAHFAs. |
HostingRepository | PRIDE |
AnnounceDate | 2020-03-09 |
AnnouncementXML | Submission_2020-03-23_06:52:36.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Kenneth Lum |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | LTQ Orbitrap Velos; LTQ Orbitrap |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-02-17 03:05:08 | ID requested | |
1 | 2020-03-09 00:26:58 | announced | |
⏵ 2 | 2020-03-23 06:52:38 | announced | 2020-03-23: Updated publication reference for PubMed record(s): 32152231. |
Publication List
Erikci Ertunc M, Kok BP, Parsons WH, Wang JG, Tan D, Donaldson CJ, Pinto AFM, Vaughan JM, Ngo N, Lum KM, Henry CL, Coppola AR, Niphakis MJ, Cravatt BF, Saez E, Saghatelian A, AIG1 and ADTRP are endogenous hydrolases of fatty acid esters of hydroxy fatty acids (FAHFAs) in mice. J Biol Chem, 295(18):5891-5905(2020) [pubmed] |
Keyword List
submitter keyword: FAHFA, threonine hydrolase, metabolism, AIG1, ADTRP, lipid, enzyme inhibitor, diabetes |
Contact List
Alan Saghatelian |
contact affiliation | Clayton Foundation Laboratories for Peptide Biology The Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla, CA, USA |
contact email | asaghatelian@salk.edu |
lab head | |
Kenneth Lum |
contact affiliation | Lundbeck La Jolla Resesarch Center |
contact email | lummyk@gmail.com |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD017539
- Label: PRIDE project
- Name: AIG1 and ADTRP are endogenous FAHFA hydrolases