title: Deletion of ELOVL6 blocks the synthesis of oleic acid but does not prevent the development of fatty liver or insulin resistance.
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.
authors.affiliation: Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046.
authors.forename: Young-Ah
authors.initials: YA
authors.lastname: Moon
authors.affiliation: Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046.
authors.forename: Courtney R
authors.initials: CR
authors.lastname: Ochoa
authors.affiliation: Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Mitsche
authors.affiliation: Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Hammer
authors.affiliation: Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046 Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046.
authors.forename: Jay D
authors.initials: JD
authors.lastname: Horton
mesh_terms: D000123:Acetyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002678:Chimera; D002999:Clone Cells; D003433:Crosses, Genetic; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000209:etiology / Q000378:metabolism*; D018752:Diet, Fat-Restricted / Q000009:adverse effects; D059305:Diet, High-Fat / Q000009:adverse effects; D004040:Dietary Carbohydrates / Q000009:adverse effects; D053595:Embryonic Stem Cells / Q000166:cytology / Q000201:enzymology; D000081031:Fatty Acid Elongases; D055786:Gene Knockout Techniques; D007333:Insulin Resistance; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications / Q000209:etiology / Q000378:metabolism*; D009765:Obesity / Q000150:complications / Q000209:etiology / Q000378:metabolism*; D019301:Oleic Acid / Q000378:metabolism*; D009829:Oleic Acids / Q000378:metabolism
chemical_list: D004040:Dietary Carbohydrates; C000630968:Elovl6 protein, mouse; D009829:Oleic Acids; D019301:Oleic Acid; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases; C050413:11-octadecenoic acid
keywords: fatty acid elongation; palmitic acid; sterol-regulatory element binding proteins