PXD017539

PXD017539 is an original dataset announced via ProteomeXchange.

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

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.

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]

submitter keyword: FAHFA, threonine hydrolase, metabolism, AIG1, ADTRP, lipid, enzyme inhibitor, diabetes

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

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PRIDE project URI

• PRIDE
  1. PXD017539
     1. Label: PRIDE project
     2. Name: AIG1 and ADTRP are endogenous FAHFA hydrolases