文章基本信息

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 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：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 rolein hepatic and whole body lipid composition. We examined therole that key transcription factors played in the control ofhepatic elongase and desaturase expression. Studies with peroxisomeproliferator-activated receptor ${alpha}$ (PPAR ${alpha}$ )-deficient mice establishthat PPAR ${alpha}$ was required for WY14643-mediated induction of fattyacid elongase-5 (Elovl-5), Elovl-6, and all three desaturases[ ${Delta}$ ⁵ desaturase ( ${Delta}$ ⁵D), ${Delta}$ ⁶D, and ${Delta}$ ⁹D]. Increased nuclear sterol-regulatoryelement binding protein-1 (SREBP-1) correlated with enhancedexpression of Elovl-6, ${Delta}$ ⁵D, ${Delta}$ ⁶D, and ${Delta}$ ⁹D. Only ${Delta}$ ⁹D was also regulatedindependently by liver X receptor (LXR) agonist. Glucose inductionof L-type pyruvate kinase, ${Delta}$ ⁹D, and Elovl-6 expression requiredthe carbohydrate-regulatory element binding protein/MAX-likefactor X (ChREBP/MLX) heterodimer. Suppression of Elovl-6 and ${Delta}$ ⁹D expression in livers of streptozotocin-induced diabetic ratsand high fat-fed glucose-intolerant mice correlated with lowlevels of nuclear SREBP-1. In leptin-deficient obese mice (Lep^ob/ob),increased SREBP-1 and MLX nuclear content correlated with theinduction of Elovl-5, Elovl-6, and ${Delta}$ ⁹D expression and the massiveaccumulation of monounsaturated fatty acids (18:1,n-7 and 18:1,n-9)in neutral lipids. Diabetes- and obesity-induced changes inhepatic lipid composition correlated with changes in elongaseand desaturase expression. In conclusion, these studies establisha role for PPAR ${alpha}$ , LXR, SREBP-1, ChREBP, and MLX in the controlof hepatic fatty acid elongase and desaturase expression andlipid 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