Distinct roles of adipose triglyceride lipase and hormone-sensitive lipase in the catabolism of triacylglycerol estolides

0541521 - FGÚ 2022 RIV US eng J - Journal Article
Brejchová, Kristýna - Radner, F. P. W. - Balas, L. - Palůchová, Veronika - Čajka, Tomáš - Chodounská, Hana - Kudová, Eva - Schratter, M. - Schreiber, R. - Durand, T. - Zechner, R. - Kuda, Ondřej
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. Roč. 118, č. 2 (2021), č. článku e2020999118. ISSN 0027-8424. E-ISSN 1091-6490
R&D Projects: GA ČR(CZ) GA20-00317S
Grant - others:AV ČR(CZ) LQ200111901
Program: Prémie Lumina quaeruntur
Institutional support: RVO:67985823 ; RVO:61388963
Keywords : ATGL * HSL * FAHFA * lipokine
OECD category: Biochemistry and molecular biology; Organic chemistry (UOCHB-X)
Impact factor: 12.779, year: 2021
Method of publishing: Open access
https://doi.org/10.1073/pnas.2020999118

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.
Permanent Link: http://hdl.handle.net/11104/0319081