Novel odd-chain cyclopropane fatty acids: detection in the mammalian lipidome and uptake by hepatosplanchnic tissues

Authors: SOBHI, HANY - Coppin State University; MERCER, KELLY - University Arkansas For Medical Sciences (UAMS); LAN, RENNY - University Arkansas For Medical Sciences (UAMS); Yeruva, Venkat; TEN HAVE, GABRIELLA - Texas A&M University; DEUTZ, NICOLAAS - Texas A&M University; PICCOLO, BRIAN - Arkansas Children'S Nutrition Research Center (ACNC); ADAMS, SEAN - Arkansas Children'S Nutrition Research Center (ACNC)

Submitted to: Journal of Lipid Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/20/2024
Publication Date: 8/27/2024
Citation: Sobhi, H.F., Mercer, K.E., Lan, R.S., Yeruva, V., Ten Have, G.A., Deutz, N.E., Piccolo, B.D., Adams, S.S. 2024. Novel odd-chain cyclopropane fatty acids: detection in the mammalian lipidome and uptake by hepatosplanchnic tissues. Journal of Lipid Research. 65(10).Article 100632. https://doi.org/10.1016/j.jlr.2024.100632.
DOI: https://doi.org/10.1016/j.jlr.2024.100632

Interpretive Summary: Microbial molecules (xenomolecules or xenometabolites) found in foods or produced by gut microbiota (natural milieu of gut) are increasingly implicated in microbe-microbe and microbe-host communication. Xenolipids, in particular, are a class of metabolites for which the full catalog remains to be elaborated in mammalian systems. To identify the xenolipids (cyclopropane fatty acids, CpFAs) in biological samples we prepared standards by chemical synthesis. Using these standards in mass spectrometry analyses, proof-of-principle studies determined presence/absence of these xenolipids in piglet biospecimens. Both CpFAs were detected in lower gut (rectal contents), serum, and liver. Archived mass spectra data from a second, independent study that used tissue-specific catheterization to monitor net metabolite flux in growing pigs confirmed the presence of both CpFAs (in plasma). These experiments also revealed a significant net uptake of the odd-chain CpFAs across the splanchnic tissue bed and liver. The results confirm that the novel xenolipids are components of the mammalian lipidome.

Technical Abstract: Microbe-produced molecules (xenometabolites)found in foods or produced by gut microbiota are increasingly implicated in microbemicrobe and microbe-host communication. Xenolipids, in particular, are a class of metabolites for which the full catalog remains to be elaborated in mammalian systems. We and others have observed that cis-3,4-methylene-heptanoylcarnitine is a lipid derivative that is one of the most abundant mediumchain acylcarnitines in human blood, hypothesized to be a product of incomplete ß-oxidation of one or more “odd-chain” long-chain cyclopropane fatty acids (CpFAs). We deduced two possible candidates, cis-11,12-methylene-pentadecanoic acid (cis-11,12-MPD) and cis-13,14-methylene-heptadecanoic acid (cis-13,14-MHD). Authentic standards were synthesized: cis-11-pentadecenoic acid and cis-13-heptadecenoic acid were generated (using Jones reagent) from cis-11-pentadecene-1-ol and cis-13-heptadecene-1-ol, respectively, and these were converted to CpFAs via a reaction involving diiodomethane. Using these standards in mass spectrometry analyses, we determined the presence/absence of cis-11,12-MPD and cis-13,14-MHD in archived piglet biospecimens. Both CpFAs were detected in rectal contents of sow and soy-fed piglets. Archived mass spectra were analyzed post hoc from a second independent study that used tissue-specific catheterization to monitor net metabolite flux in growing pigs. This confirmed the presence of both CpFAs in plasma and revealed a significant net uptake of the odd-chain CpFAs across the splanchnic tissue bed and liver. The results confirm that the novel xenolipids cis-11,12-MPD and cis-13,14-MHD can be components of the mammalian lipidome and are viable candidate precursors of cis-3,4-methylene-heptanoylcarnitine produced from partial ß-oxidation in liver or other tissues.