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DOI10.1073/pnas.2020999118
Distinct roles of adipose triglyceride lipase and hormone-sensitive lipase in the catabolism of triacylglycerol estolides
Brejchova K.; Radner F.P.W.; Balas L.; Paluchova V.; Cajka T.; Chodounska H.; Kudova E.; Schratter M.; Schreiber R.; Durand T.; Zechner R.; Kuda O.
发表日期2021
ISSN00278424
卷号118期号:2
英文摘要Branched esters of palmitic acid and hydroxy stearic acid are antiinflammatory and antidiabetic lipokines that belong to a family of fatty acid (FA) esters of hydroxy fatty acids (HFAs) called FAHFAs. FAHFAs themselves belong to oligomeric FA esters, known as estolides. Glycerol-bound FAHFAs in triacylglycerols (TAGs), named TAG estolides, serve as metabolite reservoir of FAHFAs mobilized by lipases upon demand. Here, we characterized the involvement of two major metabolic lipases, adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), in TAG estolide and FAHFA degradation. We synthesized a library of 20 TAG estolide isomers with FAHFAs varying in branching position, chain length, saturation grade, and position on the glycerol backbone and developed an in silico mass spectra library of all predicted catabolic intermediates. We found that ATGL alone or coactivated by comparative gene identification-58 efficiently liberated FAHFAs from TAG estolides with a preference for more compact substrates where the estolide branching point is located near the glycerol ester bond. ATGL was further involved in transesterification and remodeling reactions leading to the formation of TAG estolides with alternative acyl compositions. HSL represented a much more potent estolide bond hydrolase for both TAG estolides and free FAHFAs. FAHFA and TAG estolide accumulation in white adipose tissue of mice lacking HSL argued for a functional role of HSL in estolide catabolism in vivo. Our data show that ATGL and HSL participate in the metabolism of estolides and TAG estolides in distinct manners and are likely to affect the lipokine function of FAHFAs. © 2021 National Academy of Sciences. All rights reserved.
英文关键词ATGL; FAHFA; HSL; Lipokine
语种英语
scopus关键词fatty acid derivative; fatty acid esters of hydroxy fatty acid; glycerol; hormone sensitive lipase; triacylglycerol; triacylglycerol estolide; triacylglycerol lipase; unclassified drug; animal experiment; animal tissue; Article; catabolism; chemical bond; chemical structure; computer model; enzyme activity; fatty acid metabolism; gene identification; human; human cell; isomer; lipid metabolism; lipogenesis; mass spectrometry; mouse; nonhuman; priority journal; transesterification; white adipose tissue
来源期刊Proceedings of the National Academy of Sciences of the United States of America
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/181050
作者单位Institute of Physiology, Czech Academy of Sciences, Prague 4, 142 20, Czech Republic; Institute of Molecular Biosciences, University of Graz, Graz, 8010, Austria; Institut des Biomolécules Max Mousseron, UMR 5247, CNRS, École Nationale Supérieure de Chimie de Montpellier, Faculté de Pharmacie, Université de Montpellier, Montpellier, 34093, France; Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague 6, 166 10, Czech Republic; BioTechMed-Graz, Graz, 8010, Austria
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Brejchova K.,Radner F.P.W.,Balas L.,et al. Distinct roles of adipose triglyceride lipase and hormone-sensitive lipase in the catabolism of triacylglycerol estolides[J],2021,118(2).
APA Brejchova K..,Radner F.P.W..,Balas L..,Paluchova V..,Cajka T..,...&Kuda O..(2021).Distinct roles of adipose triglyceride lipase and hormone-sensitive lipase in the catabolism of triacylglycerol estolides.Proceedings of the National Academy of Sciences of the United States of America,118(2).
MLA Brejchova K.,et al."Distinct roles of adipose triglyceride lipase and hormone-sensitive lipase in the catabolism of triacylglycerol estolides".Proceedings of the National Academy of Sciences of the United States of America 118.2(2021).
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