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

Microbe-produced molecules (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 is a lipid derivative that is one of the most abundant medium-chain acylcarnitines in human blood, hypothesized to be a product of incomplete β-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 β-oxidation in liver or other tissues.