Deletion of ELOVL6 blocks the synthesis of oleic acid but does not prevent the development of fatty liver or insulin resistance

Young Ah Moon, Courtney R. Ochoa, Matthew A Mitsche, Robert E Hammer, Jay D Horton

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Elongation of very long chain fatty acid-like family member 6 (ELOVL6) is a fatty acyl elongase that performs the initial and rate-limiting condensing reaction required for microsomal elongation of long-chain fatty acids. Our previous in vitro studies suggested that ELOVL6 elongated long-chain saturated fatty acids and monounsaturated fatty acids with chain lengths of 12 to 16 carbons. Here, we describe the generation and phenotypic characterization of Elovl6-/- mice. As predicted from the in vitro studies, livers from Elovl6-/- mice accumulated palmitic (C16:0) and palmitoleic (C16:1, n-7) fatty acids and contained significantly less stearic (C18:0) and oleic (C18:1, n-9) acids, confirming that ELOVL6 is the only enzyme capable of elongating palmitate (C16:0). Unexpectedly, Elovl6-/- mice produced vaccenic acid (C18:1, n-7), the elongated product of palmitoleate (C16:1, n-7), suggesting that palmitoleate (C16:1, n-7) to vaccenate (C18:1, n-7) elongation was not specific to ELOVL6. The only detected consequence of deleting Elovl6-/- in mice was that their livers accumulated significantly more triglycerides than wild-type mice when fed a fat-free/high-carbohydrate diet. When mice were fed a high-fat diet or ELOVL6 was deleted in ob/ ob mice, the absence of ELOVL6 did not alter the development of obesity, fatty liver, hyperglycemia, or hyperinsulinemia. Combined, these results suggest that palmitoleic (C16:1, n-7) and vaccenic (C18:1, n-7) acids can largely replace the roles of oleic acid (C18:1, n-9) in vivo and that the deletion of ELOVL6 does not protect mice from the development of hepatic steatosis or insulin resistance. -Moon, Y-A., C. R. Ochoa, M. A. Mitsche, R. E. Hammer, and J. D. Horton. Deletion of ELOVL6 blocks the synthesis of oleic acid but does not prevent the development of fatty liver or insulin resistance.

Original languageEnglish (US)
Article numberA16
Pages (from-to)2597-2605
Number of pages9
JournalJournal of lipid research
Volume55
Issue number12
DOIs
StatePublished - Jan 1 2015

Keywords

  • Fatty acid elongation
  • Palmitic acid
  • Sterol-regulatory element binding proteins

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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