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Elevated hepatic fatty acid elongase-5 activity affects multiple pathways controlling hepatic lipid and carbohydrate composition 总被引:4,自引:0,他引:4
Wang Y Torres-Gonzalez M Tripathy S Botolin D Christian B Jump DB 《Journal of lipid research》2008,49(7):1538-1552
Hepatic fatty acid elongase-5 (Elovl-5) plays an important role in long chain monounsaturated and polyunsaturated fatty acid synthesis. Elovl-5 activity is regulated during development, by diet, hormones, and drugs, and in chronic disease. This report examines the impact of elevated Elovl-5 activity on hepatic function. Adenovirus-mediated induction of Elovl5 activity in livers of C57BL/6 mice increased hepatic and plasma levels of dihomo-gamma-linolenic acid (20:3,n-6) while suppressing hepatic arachidonic acid (20:4,n-6) and docosahexaenoic acid (22:6,n-3) content. The fasting-refeeding response of peroxisome proliferator-activated receptor alpha-regulated genes was attenuated in mice with elevated Elovl5 activity. In contrast, the fasting-refeeding response of hepatic sterol-regulatory element binding protein-1 (SREBP-1)-regulated and carbohydrate-regulatory element binding protein/Max-like factor X-regulated genes, Akt and glycogen synthase kinase (Gsk)-3beta phosphorylation, and the accumulation of hepatic glycogen content and nuclear SREBP-1 were not impaired by elevated Elovl5 activity. Hepatic triglyceride content and the phosphorylation of AMP-activated kinase alpha and Jun kinase 1/2 were reduced by elevated Elovl5 activity. Hepatic phosphoenolpyruvate carboxykinase expression was suppressed, while hepatic glycogen content and phosphorylated Gsk-3beta were significantly increased, in livers of fasted mice with increased Elovl5 activity. As such, hepatic Elovl5 activity may affect hepatic glucose production during fasting. In summary, Elovl5-induced changes in hepatic fatty acid content affect multiple pathways regulating hepatic lipid and carbohydrate composition. 相似文献
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The E-box like sterol regulatory element mediates the suppression of human Delta-6 desaturase gene by highly unsaturated fatty acids 总被引:3,自引:0,他引:3
Nara TY He WS Tang C Clarke SD Nakamura MT 《Biochemical and biophysical research communications》2002,296(1):111-117
Delta-6 Desaturase (D6D) catalyzes the first step of the synthesis of highly unsaturated fatty acids (HUFA) that play pivotal roles in many biological functions. The D6D expression is under feedback regulation by dietary HUFA. We co-transfected D6D promoter-reporter constructs to HepG2 cells with an expression vector of nuclear form sterol regulatory element binding protein-1c (SREBP-1c). A 90-bp region of the D6D promoter was required for the activation by SREBP-1c as well as for the suppression of the promoter activity by HUFA. The region contained two candidates of sterol regulatory element (SRE). Mutation analysis identified E-box like SRE (SRE-2) as essential for both SREBP-1c activation and HUFA suppression. SRE-2 has a core sequence of CAGCAG, and is also conserved in stearoyl CoA desatruases. Because HUFA are primarily incorporated into phospholipids (PL), our results suggest that the primary role of SREBP-1c in liver is the regulation of fatty acid supply for PL rather than for triglycerides. 相似文献
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Direct and indirect mechanisms for regulation of fatty acid synthase gene expression by liver X receptors. 总被引:28,自引:0,他引:28
Sean B Joseph Bryan A Laffitte Parthive H Patel Michael A Watson Karen E Matsukuma Robert Walczak Jon L Collins Timothy F Osborne Peter Tontonoz 《The Journal of biological chemistry》2002,277(13):11019-11025
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Diminished hepatic response to fasting/refeeding and liver X receptor agonists in mice with selective deficiency of sterol regulatory element-binding protein-1c. 总被引:24,自引:0,他引:24
Guosheng Liang Jian Yang Jay D Horton Robert E Hammer Joseph L Goldstein Michael S Brown 《The Journal of biological chemistry》2002,277(11):9520-9528
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Dual regulation of mouse Delta(5)- and Delta(6)-desaturase gene expression by SREBP-1 and PPARalpha. 总被引:8,自引:0,他引:8
Takashi Matsuzaka Hitoshi Shimano Naoya Yahagi Michiyo Amemiya-Kudo Tomohiro Yoshikawa Alyssa H Hasty Yoshiaki Tamura Jun-ichi Osuga Hiroaki Okazaki Yoko Iizuka Akimitsu Takahashi Hirohito Sone Takanari Gotoda Shun Ishibashi Nobuhiro Yamada 《Journal of lipid research》2002,43(1):107-114
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Dietary polyunsaturated fatty acids and regulation of gene transcription 总被引:18,自引:0,他引:18
Jump DB 《Current opinion in lipidology》2002,13(2):155-164