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  • 标题:Regulation of hepatic fatty acid elongase and desaturase expression in diabetes and obesity
  • 本地全文:下载
  • 作者:Wang, Yun ; Botolin, Daniela ; Xu, Jinghua
  • 期刊名称:JLR Papers In Press
  • 印刷版ISSN:0022-2275
  • 电子版ISSN:1539-7262
  • 出版年度:2006
  • 卷号:47
  • 期号:9
  • 页码:2028-2041
  • DOI:10.1194/jlr.M600177-JLR200
  • 出版社:American Society for Biochemistry and Molecular Biology
  • 摘要:Fatty acid elongases and desaturases play an important role in hepatic and whole body lipid composition. We examined the role that key transcription factors played in the control of hepatic elongase and desaturase expression. Studies with peroxisome proliferator-activated receptor {alpha} (PPAR{alpha})-deficient mice establish that PPAR{alpha} was required for WY14643-mediated induction of fatty acid elongase-5 (Elovl-5), Elovl-6, and all three desaturases [{Delta}5 desaturase ({Delta}5D), {Delta}6D, and {Delta}9D]. Increased nuclear sterol-regulatory element binding protein-1 (SREBP-1) correlated with enhanced expression of Elovl-6, {Delta}5D, {Delta}6D, and {Delta}9D. Only {Delta}9D was also regulated independently by liver X receptor (LXR) agonist. Glucose induction of L-type pyruvate kinase, {Delta}9D, and Elovl-6 expression required the carbohydrate-regulatory element binding protein/MAX-like factor X (ChREBP/MLX) heterodimer. Suppression of Elovl-6 and {Delta}9D expression in livers of streptozotocin-induced diabetic rats and high fat-fed glucose-intolerant mice correlated with low levels of nuclear SREBP-1. In leptin-deficient obese mice (Lepob/ob), increased SREBP-1 and MLX nuclear content correlated with the induction of Elovl-5, Elovl-6, and {Delta}9D expression and the massive accumulation of monounsaturated fatty acids (18:1,n-7 and 18:1,n-9) in neutral lipids. Diabetes- and obesity-induced changes in hepatic lipid composition correlated with changes in elongase and desaturase expression. In conclusion, these studies establish a role for PPAR{alpha}, LXR, SREBP-1, ChREBP, and MLX in the control of hepatic fatty acid elongase and desaturase expression and lipid composition. Supplementary key words peroxisome proliferator-activated receptor {alpha} • sterol-regulatory element binding protein-1 • carbohydrate-regulatory element binding protein • MAX-like factor X • liver X receptor Abbreviations: ACC, acetyl-coenzyme A carboxylase; ChoRE, carbohydrate-regulatory element; ChREBP, carbohydrate-regulatory element binding protein; {Delta}5D, {Delta}5 desaturase; Elovl-1, fatty acid elongase-1; HNF-4, hepatic nuclear factor-4; L-PK, L-type pyruvate kinase; Luc, luciferase; LXR, liver X receptor; MLX, MAX-like factor X; PPAR{alpha}, peroxisome proliferator-activated receptor {alpha}; qRT, quantitative real-time; SREBP-1, sterol-regulatory element binding protein-1; T1317, T0901317; T3, triiodothyronine
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