The elongation of very long-chain fatty acid 6 gene product catalyses elongation ofn-13 : 0 andn-15 : 0 odd-chain SFA in human cells

Abstract

Normal odd-chain SFA (OCSFA), particularly tridecanoic acid (n-13 : 0), pentadecanoic acid (n-15 : 0) and heptadecanoic acid (n-17 : 0), are normal components of dairy products, beef and seafood. The ratio of n-15 : 0:n-17 : 0 in ruminant foods (dairy products and beef) is 2:1, while in seafood and human tissues it is 1:2, and their appearance in plasma is often used as a marker for ruminant fat intake. Human elongases encoded by elongation of very long-chain fatty acid (ELOVL)1, ELOVL3, ELOVL6 and ELOVL7 catalyse biosynthesis of the dominant even-chain SFA; however, there are no reports of elongase function on OCSFA. ELOVL transfected MCF7 cells were treated with n-13 : 0, n-15 : 0 or n-17 : 0 (80 µm) and products analysed. ELOVL6 catalysed elongation of n-13 : 0→n-15 : 0 and n-15 : 0→n-17 : 0; and ELOVL7 had modest activity toward n-15 : 0 (n-15 : 0→n-17 : 0). No elongation activity was detected for n-17 : 0→n-19 : 0. Our data expand ELOVL specificity to OCSFA, providing the first molecular evidence demonstrating ELOVL6 as the major elongase acting on OCSFA n-13 : 0 and n-15 : 0 fatty acids. Studies of food intake relying on OCSFA as a biomarker should consider endogenous human metabolism when relying on OCSFA ratios to indicate specific food intake.

Identification of genes mediating branched chain fatty acid elongation

“…ELOVL6 is known to catalyze elongations of n‐SFA with 12, 14, and 16 carbons . Our recent study also showed ELOVL6 activity toward odd chain n‐SFA with 13 and 15 carbons . Here, we found ELOVL6 substrate specificity to BCFA anteiso ‐15:0, thus ELOVL6 has substrate specificity to both n‐SFA and BCFA with 12–16 carbons.…”

Efficacy of dietary odd-chain saturated fatty acid pentadecanoic acid parallels broad associated health benefits in humans: could it be essential?

“…Multiple studies have demonstrated that dietary C15:0 intake and associated circulating concentrations are linearly correlated 32,57,71 . This supports that, although C15:0 can be elongated from propionate or C13:0, there does not appear to be strong endogenous, de novo production of C15:0 58,72 . In addition to linear correlations between dietary and circulating C15:0 concentrations, evidence of C15:0 as a primarily exogenous fatty acid includes lack of peroxisomal 2-hydroxyacyl-CoA lyase and liver-based α-oxidation involvement in endogenous production of C15:0, lack of strong correlations between orally administered propionate with plasma C15:0 concentrations, and no evidence of effects of changing gut microbiota on circulating C15:0 57,72,73 .…”

“…Further, our studies demonstrate that ingestion of C15:0 alone increases both C15:0 and C17:0 plasma concentrations in vivo, suggesting that ingestion of C15:0 may offer benefits of both raised circulating C15:0 and C17:0, including improved glucose control. Elongation of C15:0 to C17:0 has been demonstrated in MCF7 human cells transfected with human elongases encoded by elongation of very long-chain fatty acid 6 (ELOVL6), as well as ELOVL7, providing a feasible mechanism for increased C17:0 concentrations following C15:0 ingestion 58 .…”

Plasma Docosahexaenoic Acid and Eicosapentaenoic Acid Concentrations Are Positively Associated with Brown Adipose Tissue Activity in Humans

“…This is consistent with an increase in BAT NEFA oxidation as a response to cold-induced thermogenesis [ 43 , 44 ]. The observation of significant cold-induced concentration changes in most odd-chain NEFA is also of interest given the evolving understanding of odd-chain lipid synthesis and metabolism in humans [ 45 , 46 ]. Previously thought to be strictly prokaryote-derived, it is now recognized that odd-chain fatty acids can be obtained through diet [ 47 ], produced by intestinal microbiota activity [ 48 ], endogenously synthesized from propionic acid, alpha–oxidation of hydroxylated fatty acids or produced from branched chain amino acids [ 49 , 50 ].…”