共查询到20条相似文献,搜索用时 15 毫秒
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In this study, we investigate the role of liver X receptor alpha (LXR alpha) in lipogenesis in geese in order to understand the differences in hepatic steatosis mechanisms between mammals and waterfowl. Primary goose hepatocytes were isolated and treated with the LXR alpha agonist T0901317. Triglyceride (TG) accumulation, acetyl-CoA carboxylase alpha (ACC alpha) and fatty acid synthase (FAS) activities, and gene expression levels of LXR alpha, sterol regulatory element-binding proteins-1 (SREBP-1), FAS, ACC alpha and lipoprotein lipase (LPL) were measured in primary hepatocytes. We found a dose-dependent up-regulation of TG accumulation, ACC, and FAS activities and the mRNA levels of LXR alpha, SREBP-1, FAS, ACC alpha, and LPL genes in the presence of To-901317. We also found that binding of nuclear SREBP-1 to ACC alpha SRE sequence was induced by To-901317 (P < 0.05). In conclusion, LXR alpha is involved in the induction of the lipogenic pathway through activation of SREBP-1 and its target genes in goose primary hepatocytes. 相似文献
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Role of ChREBP in hepatic steatosis and insulin resistance 总被引:1,自引:0,他引:1
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Horton JD Shimomura I Ikemoto S Bashmakov Y Hammer RE 《The Journal of biological chemistry》2003,278(38):36652-36660
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Tomohiro Yoshikawa Hitoshi Shimano Naoya Yahagi Tomohiro Ide Michiyo Amemiya-Kudo Takashi Matsuzaka Masanori Nakakuki Sachiko Tomita Hiroaki Okazaki Yoshiaki Tamura Yoko Iizuka Ken Ohashi Akimitsu Takahashi Hirohito Sone Jun-ichi Osuga Ji Takanari Gotoda Shun Ishibashi Nobuhiro Yamada 《The Journal of biological chemistry》2002,277(3):1705-1711
Previous studies have demonstrated that polyunsaturated fatty acids (PUFAs) suppress sterol regulatory element-binding protein 1c (SREBP-1c) expression and, thus, lipogenesis. In the current study, the molecular mechanism for this suppressive effect was investigated with luciferase reporter gene assays using the SREBP-1c promoter in HEK293 cells. Consistent with previous data, the addition of PUFAs to the medium in the assays robustly inhibited the SREBP-1c promoter activity. Deletion and mutation of the two liver X receptor (LXR)-responsive elements (LXREs) in the SREBP-1c promoter region eliminated this suppressive effect, indicating that both LXREs are important PUFA-suppressive elements. The luciferase activities of both SREBP-1c promoter and LXRE enhancer constructs induced by co-expression of LXRalpha or -beta were strongly suppressed by the addition of various PUFAs (arachidonic acid > eicosapentaenoic acid > docosahexaenoic acid > linoleic acid), whereas saturated or mono-unsaturated fatty acids had minimal effects. Gel shift mobility and ligand binding domain activation assays demonstrated that PUFA suppression of SREBP-1c expression is mediated through its competition with LXR ligand in the activation of the ligand binding domain of LXR, thereby inhibiting binding of LXR/retinoid X receptor heterodimer to the LXREs in the SREBP-1c promoter. These data suggest that PUFAs could be deeply involved in nutritional regulation of cellular fatty acid levels by inhibiting an LXR-SREBP-1c system crucial for lipogenesis. 相似文献
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Park HS Jeon BH Woo SH Leem J Jang JE Cho MS Park IS Lee KU Koh EH 《Molecules and cells》2011,32(6):571-577
Methionine and choline-deficient diet (MCD)-induced fatty liver is one of the best-studied animal models of fatty liver disease.
The present study was performed to clarify the relative contributions of individual lipid metabolic pathways to the pathogenesis
of MCD-induced fatty liver. Hepatic lipogenesis mediated by the sterol regulatory element-binding protein (SREBP-1c) was increased
at 1 week, but not at 6 weeks, of MCD feeding. On the other hand, 14C-palmitate oxidation did not change at 1 week, but significantly decreased at 6 weeks. This decrease was associated with
increased expression of fatty acid translocase, a key enzyme involved in fatty acid uptake. Expression of endoplasmic reticulum
stress markers was increased in mice given MCD for both 1 and 6 weeks. These findings suggest the presence of time-dependent
differences in lipid metabolism in MCD-induced fatty liver disease: SREBP-1c-mediated lipogenesis is important in the early
stages of fatty liver disease, whereas increased fatty acid uptake and decreased fatty acid oxidation become more important
in the later stages. 相似文献
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AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice 总被引:2,自引:0,他引:2
Li Y Xu S Mihaylova MM Zheng B Hou X Jiang B Park O Luo Z Lefai E Shyy JY Gao B Wierzbicki M Verbeuren TJ Shaw RJ Cohen RA Zang M 《Cell metabolism》2011,13(4):376-388
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ADD-1/SREBP-1 is a major determinant of tissue differential lipogenic capacity in mammalian and avian species 总被引:7,自引:0,他引:7
Fatty acid synthase (FAS), a key lipogenic enzyme, is expressed in the two major sites of fatty acid production in the body, that is, the liver and the adipose tissue. Surprisingly, the relative contribution of these sites to lipogenesis is highly variable among species. For example, besides the situation in rodents, where liver and fat are equally active, lipogenesis in some mammals such as the pig occurs principally in adipose tissue, whereas in avian species, the liver is the main lipogenic site. We addressed the question concerning the factors determining the site of fatty acid synthesis. We show that the expression of adipocyte determination and differentiation-dependent factor 1/sterol regulatory element-binding protein (ADD-1/SREBP-1) mRNA, but not SREBP-2, is linked to FAS protein content or activity in adipose tissues and livers of pig, chicken, and rabbit. Tissue differences in ADD-1/SREBP-1 mRNA expression between species were paralleled by commensurate variations in the nuclear concentration of SREBP-1 protein. Moreover, overexpression of ADD-1/SREBP-1 by adenoviral gene transfer induces FAS in chicken adipocytes, where lipogenesis is normally low. Conversely, the expression of a dominant negative form of ADD-1/SREBP-1 in pig adipocytes downregulates FAS expression.These results reinforce the role of ADD-1/SREBP-1 as a key regulator of lipogenesis, by extending its importance to nonrodent mammals and birds. Furthermore, they establish that differential expression of ADD-1/SREBP-1 is a key determinant of the site of fatty acid synthesis in the body.-Gondret, F., P. Ferré, and I. Dugail. ADD-1/SREBP-1 is a major determinant of tissue differential lipogenic capacity in mammalian and avian species. J. Lipid Res. 2001. 42: 106;-113. 相似文献