ATGL is a biosynthetic enzyme for fatty acid esters of hydroxy fatty acids.


Journal

Nature
ISSN: 1476-4687
Titre abrégé: Nature
Pays: England
ID NLM: 0410462

Informations de publication

Date de publication:
06 2022
Historique:
received: 30 04 2021
accepted: 21 04 2022
pubmed: 9 6 2022
medline: 2 7 2022
entrez: 8 6 2022
Statut: ppublish

Résumé

Branched fatty acid (FA) esters of hydroxy FAs (HFAs; FAHFAs) are recently discovered lipids that are conserved from yeast to mammals

Identifiants

pubmed: 35676490
doi: 10.1038/s41586-022-04787-x
pii: 10.1038/s41586-022-04787-x
pmc: PMC9242854
doi:

Substances chimiques

Diglycerides 0
Esters 0
Fatty Acids 0
Hydroxy Acids 0
Triglycerides 0
Acyltransferases EC 2.3.-
PNPLA2 protein, human EC 3.1.1.3
PNPLA2 protein, mouse EC 3.1.1.3

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

968-975

Subventions

Organisme : NIH HHS
ID : S10 OD021815
Pays : United States
Organisme : NIDDK NIH HHS
ID : F30 DK112622
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK106210
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK046200
Pays : United States
Organisme : NIDDK NIH HHS
ID : K01 DK128075
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK057521
Pays : United States
Organisme : NIDDK NIH HHS
ID : R56 DK043051
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK007516
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA014195
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007374
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK043051
Pays : United States

Informations de copyright

© 2022. The Author(s).

Références

Yore, M. M. et al. Discovery of a class of endogenous mammalian lipids with anti-diabetic and anti-inflammatory effects. Cell 159, 318–332 (2014).
pubmed: 25303528 pmcid: 4260972 doi: 10.1016/j.cell.2014.09.035
Celis Ramirez, A. M. et al. Analysis of Malassezia lipidome disclosed differences among the species and reveals presence of unusual yeast lipids. Front. Cell. Infect. Microbiol. 10, 338 (2020).
pubmed: 32760678 pmcid: 7374198 doi: 10.3389/fcimb.2020.00338
Brejchova, K. et al. Understanding FAHFAs: from structure to metabolic regulation. Prog. Lipid Res. 79, 101053 (2020).
pubmed: 32735891 doi: 10.1016/j.plipres.2020.101053
Lee, J. et al. Branched fatty acid esters of hydroxy fatty acids (FAHFAs) protect against colitis by regulating gut innate and adaptive immune responses. J. Biol. Chem. 291, 22207–22217 (2016).
pubmed: 27573241 pmcid: 5064000 doi: 10.1074/jbc.M115.703835
Syed, I. et al. Palmitic acid hydroxystearic acids activate GPR40, which is involved in their beneficial effects on glucose homeostasis. Cell Metab. 27, 419–427 (2018).
pubmed: 29414687 pmcid: 5807007 doi: 10.1016/j.cmet.2018.01.001
Syed, I. et al. PAHSAs attenuate immune responses and promote beta cell survival in autoimmune diabetic mice. J. Clin. Invest. 129, 3717–3731 (2019).
pubmed: 31380811 pmcid: 6715391 doi: 10.1172/JCI122445
Zhou, P. et al. PAHSAs enhance hepatic and systemic insulin sensitivity through direct and indirect mechanisms. J. Clin. Invest. 129, 4138–4150 (2019).
pubmed: 31449056 pmcid: 6763232 doi: 10.1172/JCI127092
Zhu, Q. F., Yan, J. W., Ni, J. & Feng, Y. Q. FAHFA footprint in the visceral fat of mice across their lifespan. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 1865, 158639 (2020).
pubmed: 31988049 doi: 10.1016/j.bbalip.2020.158639
Brezinova, M. et al. Levels of palmitic acid ester of hydroxystearic acid (PAHSA) are reduced in the breast milk of obese mothers. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 1863, 126–131 (2018).
pubmed: 29154942 doi: 10.1016/j.bbalip.2017.11.004
Zhu, Q. F. et al. Highly sensitive determination of fatty acid esters of hydroxyl fatty acids by liquid chromatography-mass spectrometry. J. Chromatogr. B 1061-1062, 34–40 (2017).
doi: 10.1016/j.jchromb.2017.06.045
Brezinova, M. et al. Exercise training induces insulin-sensitizing PAHSAs in adipose tissue of elderly women. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 1865, 158576 (2020).
pubmed: 31740387 doi: 10.1016/j.bbalip.2019.158576
Dongoran, R. A. et al. Determination of major endogenous FAHFAs in healthy human circulation: the correlations with several circulating cardiovascular-related biomarkers and anti-inflammatory effects on RAW 264.7 cells. Biomolecules 10, 1689 (2020).
pmcid: 7766943 doi: 10.3390/biom10121689
Wen, X. H., Guo, Q. L. & Guo, J. C. Effect of 9-PAHSA on cognitive dysfunction in diabetic mice and its possible mechanism. Biochem. Biophys. Res. Commun. 524, 525–532 (2020).
pubmed: 32014256 doi: 10.1016/j.bbrc.2020.01.071
Kuda, O. et al. Docosahexaenoic acid-derived fatty acid esters of hydroxy fatty acids (FAHFAs) with anti-inflammatory properties. Diabetes 65, 2580–2590 (2016).
pubmed: 27313314 doi: 10.2337/db16-0385
Kolar, M. J. et al. Linoleic acid esters of hydroxy linoleic acids are anti-inflammatory lipids found in plants and mammals. J. Biol. Chem. 294, 10698–10707 (2019).
pubmed: 31152059 pmcid: 6615670 doi: 10.1074/jbc.RA118.006956
Benlebna, M. et al. Long-term intake of 9-PAHPA or 9-OAHPA modulates favorably the basal metabolism and exerts an insulin sensitizing effect in obesogenic diet-fed mice. Eur. J. Nutr. 60, 2013–2027 (2020).
pubmed: 32989473 doi: 10.1007/s00394-020-02391-1
Benlebna, M. et al. Long-term high intake of 9-PAHPA or 9-OAHPA increases basal metabolism and insulin sensitivity but disrupts liver homeostasis in healthy mice. J. Nutr. Biochem. 79, 108361 (2020).
pubmed: 32179409 doi: 10.1016/j.jnutbio.2020.108361
Kolar, M. J. et al. Branched fatty acid esters of hydroxy fatty acids are preferred substrates of the MODY8 protein carboxyl ester lipase. Biochemistry 55, 4636–4641 (2016).
pubmed: 27509211 doi: 10.1021/acs.biochem.6b00565
Parsons, W. H. et al. AIG1 and ADTRP are atypical integral membrane hydrolases that degrade bioactive FAHFAs. Nat. Chem. Biol. 12, 367–372 (2016).
pubmed: 27018888 pmcid: 4837090 doi: 10.1038/nchembio.2051
Brejchova, K. et al. Distinct roles of adipose triglyceride lipase and hormone-sensitive lipase in the catabolism of triacylglycerol estolides. Proc. Natl Acad. Sci. USA 118, e2020999118 (2021).
pubmed: 33372146 doi: 10.1073/pnas.2020999118
Kuda, O. et al. Nrf2-mediated antioxidant defense and peroxiredoxin 6 are linked to biosynthesis of palmitic acid ester of 9-hydroxystearic acid. Diabetes 67, 1190–1199 (2018).
pubmed: 29549163 pmcid: 6463562 doi: 10.2337/db17-1087
Bachovchin, D. A. et al. Superfamily-wide portrait of serine hydrolase inhibition achieved by library-versus-library screening. Proc. Natl Acad. Sci. USA 107, 20941–20946 (2010).
pubmed: 21084632 pmcid: 3000285 doi: 10.1073/pnas.1011663107
Liu, Y., Patricelli, M. P. & Cravatt, B. F. Activity-based protein profiling: the serine hydrolases. Proc. Natl Acad. Sci. USA 96, 14694–14699 (1999).
pubmed: 10611275 pmcid: 24710 doi: 10.1073/pnas.96.26.14694
Jessani, N. et al. A streamlined platform for high-content functional proteomics of primary human specimens. Nat. Methods 2, 691–697 (2005).
pubmed: 16118640 doi: 10.1038/nmeth778
Galmozzi, A., Dominguez, E., Cravatt, B. F. & Saez, E. Application of activity-based protein profiling to study enzyme function in adipocytes. Methods Enzymol. 538, 151–169 (2014).
pubmed: 24529438 pmcid: 4138146 doi: 10.1016/B978-0-12-800280-3.00009-8
Schreiber, R., Xie, H. & Schweiger, M. Of mice and men: the physiological role of adipose triglyceride lipase (ATGL). Biochim. Biophys. Acta Mol. Cell Biol. Lipids 1864, 880–899 (2019).
pubmed: 30367950 pmcid: 6439276 doi: 10.1016/j.bbalip.2018.10.008
Tan, D. et al. Discovery of FAHFA-containing triacylglycerols and their metabolic regulation. J. Am. Chem. Soc. 141, 8798–8806 (2019).
pubmed: 31056915 pmcid: 6662584 doi: 10.1021/jacs.9b00045
Paluchova, V. et al. Lipokine 5-PAHSA is regulated by adipose triglyceride lipase and primes adipocytes for de novo lipogenesis in mice. Diabetes 69, 300–312 (2020).
pubmed: 31806624 pmcid: 7118252 doi: 10.2337/db19-0494
Zimmermann, R. et al. Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase. Science 306, 1383–1386 (2004).
pubmed: 15550674 doi: 10.1126/science.1100747
Jenkins, C. M. et al. Identification, cloning, expression, and purification of three novel human calcium-independent phospholipase A2 family members possessing triacylglycerol lipase and acylglycerol transacylase activities. J. Biol. Chem. 279, 48968–48975 (2004).
pubmed: 15364929 doi: 10.1074/jbc.M407841200
Villena, J. A., Roy, S., Sarkadi-Nagy, E., Kim, K. H. & Sul, H. S. Desnutrin, an adipocyte gene encoding a novel patatin domain-containing protein, is induced by fasting and glucocorticoids: ectopic expression of desnutrin increases triglyceride hydrolysis. J. Biol. Chem. 279, 47066–47075 (2004).
pubmed: 15337759 doi: 10.1074/jbc.M403855200
Taschler, U. et al. Adipose triglyceride lipase is involved in the mobilization of triglyceride and retinoid stores of hepatic stellate cells. Biochim. Biophys. Acta 1851, 937–945 (2015).
pubmed: 25732851 pmcid: 4408194 doi: 10.1016/j.bbalip.2015.02.017
Notari, L. et al. Identification of a lipase-linked cell membrane receptor for pigment epithelium-derived factor. J. Biol. Chem. 281, 38022–38037 (2006).
pubmed: 17032652 doi: 10.1074/jbc.M600353200
Zhang, X. et al. An epistatic interaction between Pnpla2 and Lipe reveals new pathways of adipose tissue lipolysis. Cells 8, 395 (2019).
pmcid: 6563012 doi: 10.3390/cells8050395
Ohno, Y., Kamiyama, N., Nakamichi, S. & Kihara, A. PNPLA1 is a transacylase essential for the generation of the skin barrier lipid ω-O-acylceramide. Nat. Commun. 8, 14610 (2017).
pubmed: 28248318 pmcid: 5337975 doi: 10.1038/ncomms14610
Grond, S. et al. PNPLA1 deficiency in mice and humans leads to a defect in the synthesis of omega-O-acylceramides. J. Invest. Dermatol. 137, 394–402 (2017).
pubmed: 27751867 doi: 10.1016/j.jid.2016.08.036
Lass, A. et al. Adipose triglyceride lipase-mediated lipolysis of cellular fat stores is activated by CGI-58 and defective in Chanarin-Dorfman Syndrome. Cell Metab. 3, 309–319 (2006).
pubmed: 16679289 doi: 10.1016/j.cmet.2006.03.005
Kulminskaya, N. et al. Optimized expression and purification of adipose triglyceride lipase improved hydrolytic and transacylation activities in vitro. J. Biol. Chem. 297, 101206 (2021).
pubmed: 34543623 pmcid: 8506970 doi: 10.1016/j.jbc.2021.101206
Schoiswohl, G. et al. Impact of reduced ATGL-mediated adipocyte lipolysis on obesity-associated insulin resistance and inflammation in male mice. Endocrinology 156, 3610–3624 (2015).
pubmed: 26196542 pmcid: 4588821 doi: 10.1210/en.2015-1322
Perry, R. J. et al. Hepatic acetyl CoA links adipose tissue inflammation to hepatic insulin resistance and type 2 diabetes. Cell 160, 745–758 (2015).
pubmed: 25662011 pmcid: 4498261 doi: 10.1016/j.cell.2015.01.012
Ahmadian, M. et al. Adipose overexpression of desnutrin promotes fatty acid use and attenuates diet-induced obesity. Diabetes 58, 855–866 (2009).
pubmed: 19136649 pmcid: 2661591 doi: 10.2337/db08-1644
Jocken, J. W. et al. Adipose triglyceride lipase and hormone-sensitive lipase protein expression is decreased in the obese insulin-resistant state. J. Clin. Endocrinol. Metab. 92, 2292–2299 (2007).
pubmed: 17356053 doi: 10.1210/jc.2006-1318
Nelson, A. T. et al. Stereochemistry of endogenous palmitic acid ester of 9-hydroxystearic acid and relevance of absolute configuration to regulation. J. Am. Chem. Soc. 139, 4943–4947 (2017).
pubmed: 28350171 pmcid: 5568760 doi: 10.1021/jacs.7b01269
Gruber, A. et al. The N-terminal region of comparative gene identification-58 (CGI-58) is important for lipid droplet binding and activation of adipose triglyceride lipase. J. Biol. Chem. 285, 12289–12298 (2010).
pubmed: 20164531 pmcid: 2852968 doi: 10.1074/jbc.M109.064469
Cornaciu, I. et al. The minimal domain of adipose triglyceride lipase (ATGL) ranges until leucine 254 and can be activated and inhibited by CGI-58 and G0S2, respectively. PLoS ONE 6, e26349 (2011).
pubmed: 22039468 pmcid: 3198459 doi: 10.1371/journal.pone.0026349
Cases, S. et al. Identification of a gene encoding an acyl CoA:diacylglycerol acyltransferase, a key enzyme in triacylglycerol synthesis. Proc. Natl Acad. Sci. USA 95, 13018–13023 (1998).
pubmed: 9789033 pmcid: 23692 doi: 10.1073/pnas.95.22.13018
Chitraju, C., Walther, T. C. & Farese, R. V. Jr The triglyceride synthesis enzymes DGAT1 and DGAT2 have distinct and overlapping functions in adipocytes. J. Lipid Res. 60, 1112–1120 (2019).
pubmed: 30936184 pmcid: 6547635 doi: 10.1194/jlr.M093112
Smith, S. J. et al. Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat. Nat. Genet. 25, 87–90 (2000).
pubmed: 10802663 doi: 10.1038/75651
Lee, M. J. & Fried, S. K. Optimal protocol for the differentiation and metabolic analysis of human adipose stromal cells. Methods Enzymol. 538, 49–65 (2014).
pubmed: 24529433 pmcid: 4336794 doi: 10.1016/B978-0-12-800280-3.00004-9
Martin, B. R. & Cravatt, B. F. Large-scale profiling of protein palmitoylation in mammalian cells. Nat. Methods 6, 135–138 (2009).
pubmed: 19137006 pmcid: 2775068 doi: 10.1038/nmeth.1293
He, L., Diedrich, J., Chu, Y. Y. & Yates, J. R. 3rd Extracting accurate precursor information for tandem mass spectra by RawConverter. Anal. Chem. 87, 11361–11367 (2015).
pubmed: 26499134 pmcid: 4777630 doi: 10.1021/acs.analchem.5b02721
Xu, T. et al. ProLuCID: an improved SEQUEST-like algorithm with enhanced sensitivity and specificity. J. Proteomics 129, 16–24 (2015).
pubmed: 26171723 pmcid: 4630125 doi: 10.1016/j.jprot.2015.07.001
Tabb, D. L., McDonald, W. H. & Yates, J. R. 3rd DTASelect and Contrast: tools for assembling and comparing protein identifications from shotgun proteomics. J. Proteome Res. 1, 21–26 (2002).
pubmed: 12643522 pmcid: 2811961 doi: 10.1021/pr015504q
Peng, J., Elias, J. E., Thoreen, C. C., Licklider, L. J. & Gygi, S. P. Evaluation of multidimensional chromatography coupled with tandem mass spectrometry (LC/LC-MS/MS) for large-scale protein analysis: the yeast proteome. J. Proteome Res. 2, 43–50 (2003).
pubmed: 12643542 doi: 10.1021/pr025556v
Nagy, H. M. et al. Adipose triglyceride lipase activity is inhibited by long-chain acyl-coenzyme A. Biochim. Biophys. Acta 1841, 588–594 (2014).
pubmed: 24440819 pmcid: 3988850 doi: 10.1016/j.bbalip.2014.01.005
Shepherd, P. R. et al. Adipose cell hyperplasia and enhanced glucose disposal in transgenic mice overexpressing GLUT4 selectively in adipose tissue. J. Biol. Chem. 268, 22243–22246 (1993).
pubmed: 8226728 doi: 10.1016/S0021-9258(18)41516-5
Eguchi, J. et al. Transcriptional control of adipose lipid handling by IRF4. Cell Metab. 13, 249–259 (2011).
pubmed: 21356515 pmcid: 3063358 doi: 10.1016/j.cmet.2011.02.005
Bligh, E. G. & Dyer, W. J. A rapid method of total lipid extraction and purification. Can. J. Biochem. Physiol. 37, 911–917 (1959).
pubmed: 13671378 doi: 10.1139/y59-099
Zhang, T. et al. A LC-MS-based workflow for measurement of branched fatty acid esters of hydroxy fatty acids. Nat. Protoc. 11, 747–763 (2016).
pubmed: 26985573 pmcid: 4797065 doi: 10.1038/nprot.2016.040
Patel, R. et al. LXRbeta is required for glucocorticoid-induced hyperglycemia and hepatosteatosis in mice. J. Clin. Invest. 121, 431–441 (2011).
pubmed: 21123945 doi: 10.1172/JCI41681
Maclean, B. et al. Effect of collision energy optimization on the measurement of peptides by selected reaction monitoring (SRM) mass spectrometry. Anal. Chem. 82, 10116–10124 (2010).
pubmed: 21090646 pmcid: 3005404 doi: 10.1021/ac102179j

Auteurs

Rucha Patel (R)

Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.

Anna Santoro (A)

Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.

Peter Hofer (P)

Institute of Molecular Biosciences, University of Graz, Graz, Austria.

Dan Tan (D)

Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, La Jolla, CA, USA.

Monika Oberer (M)

Institute of Molecular Biosciences, University of Graz, Graz, Austria.

Andrew T Nelson (AT)

Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California-San Diego, La Jolla, CA, USA.

Srihari Konduri (S)

Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California-San Diego, La Jolla, CA, USA.

Dionicio Siegel (D)

Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California-San Diego, La Jolla, CA, USA.

Rudolf Zechner (R)

Institute of Molecular Biosciences, University of Graz, Graz, Austria.
BioTechMed-Graz, Graz, Austria.

Alan Saghatelian (A)

Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, La Jolla, CA, USA.

Barbara B Kahn (BB)

Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA. bkahn@bidmc.harvard.edu.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH