AIG1 and ADTRP are endogenous hydrolases of fatty acid esters of hydroxy fatty acids (FAHFAs) in mice.

The Journal of Biological Chemistry
Meric Erikci ErtuncAlan Saghatelian

Abstract

Fatty acid esters of hydroxy fatty acids (FAHFAs) are a newly discovered class of signaling lipids with anti-inflammatory and anti-diabetic properties. However, the endogenous regulation of FAHFAs remains a pressing but unanswered question. Here, using MS-based FAHFA hydrolysis assays, LC-MS-based lipidomics analyses, and activity-based protein profiling, we found that androgen-induced gene 1 (AIG1) and androgen-dependent TFPI-regulating protein (ADTRP), two threonine hydrolases, control FAHFA levels in vivo in both genetic and pharmacologic mouse models. Tissues from mice lacking ADTRP (Adtrp-KO), or both AIG1 and ADTRP (DKO) had higher concentrations of FAHFAs particularly isomers with the ester bond at the 9th carbon due to decreased FAHFA hydrolysis activity. The levels of other lipid classes were unaltered indicating that AIG1 and ADTRP specifically hydrolyze FAHFAs. Complementing these genetic studies, we also identified a dual AIG1/ADTRP inhibitor, ABD-110207, which is active in vivo Acute treatment of WT mice with ABD-110207 resulted in elevated FAHFA levels, further supporting the notion that AIG1 and ADTRP activity control endogenous FAHFA levels. However, loss of AIG1/ADTRP did not mimic the changes associated with p...Continue Reading

References

Dec 28, 1999·Proceedings of the National Academy of Sciences of the United States of America·Y LiuB F Cravatt
May 16, 2000·The Journal of Biological Chemistry·A F KisselevA L Goldberg
Aug 1, 1959·Canadian Journal of Biochemistry and Physiology·E G BLIGH, W J DYER
Nov 10, 2004·Biochemistry·Alan SaghatelianBenjamin F Cravatt
Jan 18, 2005·American Journal of Pharmacogenomics : Genomics-related Research in Drug Development and Clinical Practice·Alicia B BergerMatthew Bogyo
Jun 2, 2005·American Journal of Physiology. Endocrinology and Metabolism·Eugenia CarvalhoBarbara B Kahn
Jul 27, 2006·Journal of the American Chemical Society·Jessica P Alexander, Benjamin F Cravatt
Mar 28, 2008·Annual Review of Biochemistry·Benjamin F CravattJohn W Kozarich
Nov 13, 2009·The American Journal of Clinical Nutrition·Steven A Kliewer, David J Mangelsdorf
Jun 25, 2010·Prostaglandins, Leukotrienes, and Essential Fatty Acids·W C TuR A Gibson
Nov 19, 2010·Proceedings of the National Academy of Sciences of the United States of America·Daniel A BachovchinBenjamin F Cravatt
Nov 19, 2010·Nature·Eranthie WeerapanaBenjamin F Cravatt
Oct 13, 2012·Bioinformatics·Limin FuWeizhong Li
Oct 30, 2012·Nature Chemical Biology·Ku-Lung HsuBenjamin F Cravatt
Jan 5, 2013·Science·Le CongFeng Zhang
Oct 26, 2013·Nature Protocols·F Ann RanFeng Zhang
Mar 13, 2014·Blood·Jeremy P WoodAlan E Mast
Oct 1, 2014·Proceedings of the National Academy of Sciences of the United States of America·Jordon M InloesBenjamin F Cravatt
Oct 27, 2015·Analytical Chemistry·Lin HeJohn R Yates
Nov 19, 2015·Journal of Cheminformatics·Yan MaOliver Fiehn
Mar 29, 2016·Nature Chemical Biology·William H ParsonsBenjamin F Cravatt
Mar 27, 2018·Analytical Chemistry·Matthew J KolarAlan Saghatelian
Apr 17, 2018·Cell Metabolism·Parkyong SongSteven A Kliewer
Oct 21, 2018·Biochemical and Biophysical Research Communications·Yan-Mei WangNing-Yuan Fang
Nov 6, 2018·Nucleic Acids Research·Yasset Perez-RiverolJuan Antonio Vizcaíno
Dec 21, 2018·Journal of the American Heart Association·Maulin M PatelCristina Lupu
May 7, 2019·Journal of the American Chemical Society·Dan TanAlan Saghatelian
Jun 4, 2019·The Journal of Biological Chemistry·Matthew J KolarAlan Saghatelian
Aug 6, 2019·The Journal of Clinical Investigation·Ismail SyedBarbara B Kahn
Aug 27, 2019·The Journal of Clinical Investigation·Peng ZhouBarbara B Kahn

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Citations

Sep 23, 2020·European Journal of Mass Spectrometry·Edgar White Buenger, Gavin E Reid
Nov 22, 2020·Diabetes·Veronica L LiJonathan Z Long
Jan 8, 2021·Biochimie·Melha BenlebnaChristine Feillet-Coudray
Dec 30, 2020·Proceedings of the National Academy of Sciences of the United States of America·Kristyna BrejchovaOndrej Kuda
Feb 26, 2021·Nature Reviews. Endocrinology·Pauline MorignyDominique Langin
May 1, 2021·International Journal of Molecular Sciences·Cristina LupuFlorea Lupu
Apr 2, 2021·Chembiochem : a European Journal of Chemical Biology·Yan ZhangZheng Guo
Jul 25, 2021·International Journal of Molecular Sciences·Siddabasave Gowda B GowdaShu-Ping Hui
Jul 30, 2021·Frontiers in Nutrition·Teresa KellererThomas Skurk
Aug 29, 2021·Pharmacology & Therapeutics·Martin RiecanOndrej Kuda

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