Branched and linear fatty acid esters of hydroxy fatty acids (FAHFA) relevant to human health

Hydroxy fatty acids are known to cause cell cycle arrest and apoptosis. The best studied of them, 9-hydroxystearic acid (9-HSA), induces apoptosis in cell lines by acting through mechanisms involving different targets. Using mass spectrometry-based lipidomic approaches, we show in this study that 9-HSA levels in human colorectal tumors are diminished when compared with normal adjacent tissue. Since this decrease could be compatible with an escape mechanism of tumors from 9-HSA-induced apoptosis, we investigated different features of the utilization of this hydroxyfatty acid in colon. We show that in colorectal tumors and related cell lines such as HT-29 and HCT-116, 9-HSA is the only hydroxyfatty acid constituent of branched fatty acid esters of hydroxyfatty acids (FAHFA), a novel family of lipids with anti-inflammatory properties. Importantly, FAHFA levels in tumors are elevated compared with normal tissue and, unlike 9-HSA, they do not induce apoptosis of colorectal cell lines over a wide range of concentrations. Further, the addition of 9-HSA to colon cancer cell lines augments the synthesis of different FAHFA before the cells commit to apoptosis, suggesting that FAHFA formation may function as a buffer system that sequesters the hydroxyacid into an inactive form, thereby restricting apoptosis.

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Flow Infusion Electrospray Ionization High-Resolution Mass Spectrometry of the Chloride Adducts of Sphingolipids, Glycerophospholipids, Glycerols, Hydroxy Fatty Acids, Fatty Acid Esters of Hydroxy Fatty Acids (FAHFA), and Modified Nucleosides

Neuromethods - Metabolomics ◽

10.1007/978-1-0716-0864-7_6 ◽

2020 ◽

pp. 69-76

Author(s):

Paul L. Wood ◽

Randall L. Woltjer

Keyword(s):

Mass Spectrometry ◽

Fatty Acids ◽

Fatty Acid ◽

High Resolution ◽

High Resolution Mass Spectrometry ◽

Hydroxy Fatty Acids ◽

Modified Nucleosides ◽

Fatty Acid Esters ◽

Acid Esters ◽

Resolution Mass

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Distinct biological activities of isomers from several families of branched fatty acid esters of hydroxy fatty acids (FAHFAs)

The Journal of Lipid Research ◽

10.1016/j.jlr.2021.100108 ◽

2021 ◽

Vol 62 ◽

pp. 100108

Author(s):

Pratik Aryal ◽

Ismail Syed ◽

Jennifer Lee ◽

Rucha Patel ◽

Andrew T. Nelson ◽

...

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Biological Activities ◽

Hydroxy Fatty Acids ◽

Fatty Acid Esters ◽

Acid Esters

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Branched Fatty Acid Esters of Hydroxy Fatty Acids Are Preferred Substrates of the MODY8 Protein Carboxyl Ester Lipase

Biochemistry ◽

10.1021/acs.biochem.6b00565 ◽

2016 ◽

Vol 55 (33) ◽

pp. 4636-4641 ◽

Cited By ~ 36

Author(s):

Matthew J. Kolar ◽

Siddhesh S. Kamat ◽

William H. Parsons ◽

Edwin A. Homan ◽

Tim Maher ◽

...

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Hydroxy Fatty Acids ◽

Fatty Acid Esters ◽

Acid Esters

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Moose and Caribou as Novel Sources of Functional Lipids: Fatty Acid Esters of Hydroxy Fatty Acids, Diglycerides and Monoacetyldiglycerides

Molecules ◽

10.3390/molecules24020232 ◽

2019 ◽

Vol 24 (2) ◽

pp. 232 ◽

Cited By ~ 10

Author(s):

Thu Pham ◽

Natalia Vidal ◽

Charles Manful ◽

Tiffany Fillier ◽

Ryley Pumphrey ◽

...

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Molecular Species ◽

Hydroxy Fatty Acid ◽

Inflammatory Diseases ◽

Hydroxy Fatty Acids ◽

Fatty Acid Esters ◽

Acid Moiety ◽

Molecular Species Composition ◽

Acid Esters

Fatty acid esters of hydroxy fatty acids (FAHFA), diglycerides (DG) and monoacetyldiglycerides (MAcDG) are gaining interest as functional lipids in pharmaceuticals and functional food formulations for managing and treating metabolic or inflammatory diseases. Herein, we investigated whether the antler and/or meat of two Cervids (moose and caribou) are novel sources of FAHFA, DG and MAcDG. We observed FAHFA present in moose and caribou composed mainly of polyunsaturated families, and that the esterification occurred frequently at the C5-hydroxy fatty acid moiety, most noticeably arachidonic acid 5-hydroxyeicosatrienoic acid (ARA-5-HERA). Moose antler, caribou and moose meat also contained significant levels of both 1,2-DG and 1,3-DG lipids. The 1,3-DG molecular species consisted mainly of 16:0/18:1, 18:0/16:0, and 18:0/18:1. On the other hand, major 1,2-DG species consisted of DG 18:0/18:0, 16:0/16:0 and 18:1/18:1 molecular species with higher levels in the antler compared to the meat. The molecular species composition of MAcDG was very simple and consisted of 14:2/18:2/2:0, 16:0/18:2/2:0, 16:0/18:1/2:0 and 18:0/18:1/2:0 with the first species 14:2/18:2/2:0 predominating in the tip of moose antlers. Increasing access to and knowledge of the presence of these functional lipids in foods will enhance their intake in the diet with potential implications in improving personal and population health.

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