TY - JOUR
T1 - Deletion of ELOVL6 blocks the synthesis of oleic acid but does not prevent the development of fatty liver or insulin resistance
AU - Moon, Young Ah
AU - Ochoa, Courtney R.
AU - Mitsche, Matthew A
AU - Hammer, Robert E
AU - Horton, Jay D
N1 - Publisher Copyright:
Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.
PY - 2015/1/1
Y1 - 2015/1/1
N2 - 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.
AB - 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.
KW - Fatty acid elongation
KW - Palmitic acid
KW - Sterol-regulatory element binding proteins
UR - http://www.scopus.com/inward/record.url?scp=84919776582&partnerID=8YFLogxK
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U2 - 10.1194/jlr.M054353
DO - 10.1194/jlr.M054353
M3 - Article
C2 - 25281760
AN - SCOPUS:84919776582
SN - 0022-2275
VL - 55
SP - 2597
EP - 2605
JO - Journal of lipid research
JF - Journal of lipid research
IS - 12
M1 - A16
ER -