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标题：Deletion of ELOVL6 blocks the synthesis of oleic acid but does not prevent the development of fatty liver or insulin resistance
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作者：Young-Ah Moon ; Courtney R. Ochoa ; Matthew A. Mitsche 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2014
卷号：55
期号：12
页码：2597-2605
DOI：10.1194/jlr.M054353
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：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.
关键词：fatty acid elongation ; palmitic acid ; sterol-regulatory element binding proteins