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, Laxmi; 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: N/A
Citation: N/A

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: Some microbe-produced molecules (xenomolecules or xenometabolites) found in foods or produced by gut microbiota 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. We and others have observed that cis-3,4-methylene-heptanoylcarnitine (cis-3,4-MHC) is a lipid derivative that is one of the most abundant medium-chain 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). With this in mind 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 prepared by chemical synthesis: first, 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 second, conversion to CpFAs via a reaction involving diiodomethane. Using these standards in mass spectrometry analyses, proof-of-principle studies determined presence/absence of cis-11,12-MPD and cis-13,14 MHD 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 cis-11,12-MPD and cis-13,14 MHD are components of the mammalian lipidome, and are viable candidate precursors of cis-3,4-MHC produced from partial ß-oxidation in liver or other tissues.