Microarray analysis of gene expression in liver, adipose tissue and skeletal muscle in response to chronic dietary administration of NDGA to high-fructose fed dyslipidemic rats.
Microarray analysis of gene expression in liver, adipose tissue and skeletal muscle in response to chronic dietary administration of NDGA to high-fructose fed dyslipidemic rats.
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DOI：
10.1186/s12986-016-0121-y
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发表时间：
2016
影响因子：
4.5
通讯作者：
Azhar S
中科院分区：
文献类型：
--
作者：
Zhang H;Shen WJ;Li Y;Bittner A;Bittner S;Tabassum J;Cortez YF;Kraemer FB;Azhar S
去甲二氢愈创木酸（NDGA）是木馏油的主要代谢产物，已被证明对代谢综合征的核心组分具有深远的影响，包括降低血糖、游离脂肪酸和甘油三酯水平，在几种血脂异常的啮齿动物模型中减轻血压升高，以及改善体重、胰岛素抵抗、糖尿病和高血压。在本研究中，采用高果糖饮食喂养的高胆固醇血症、血脂异常、胰岛素抵抗和肝脂肪变性大鼠模型，研究了三种胰岛素敏感组织（肝脏、骨骼肌和脂肪组织）中脂质代谢途径的整体转录变化，以响应长期饮食给予NDGA。Sprague-Dawley雄性大鼠（SD）喂食普通饲料（对照）饮食、高果糖饮食（HFrD）或补充NDGA（2.5 g/kg饮食）的HFrD 8周。饮食管理NDGA降低TG，葡萄糖和胰岛素的血浆水平，并减弱肝脏TG的积累。DNA微阵列表达谱分析表明，NDGA可上调肝脏中某些参与脂肪酸氧化的基因及其转录调节因子PPARα的表达，降低一些脂肪生成基因及其相关转录因子的表达，并对肝脏中脂肪酸转运蛋白、乙酰辅酶A合成酶、延伸酶、脂肪酸去饱和酶和脂质清除蛋白的基因产生差异性影响，骨骼肌和脂肪组织。这些发现表明，NDGA改善高脂血症和脂肪变性主要是通过抑制脂肪生成和增加脂肪酸catalysts在三个主要的胰岛素反应组织通过改变的关键酶基因和转录因子的表达参与从头脂肪生成和脂肪酸氧化。
Nordihydroguaiaretic acid (NDGA), the main metabolite of Creosote Bush, has been shown to have profound effects on the core components of metabolic syndrome, including lowering of blood glucose, free fatty acids and triglyceride levels, attenuating elevated blood pressure in several rodent models of dyslipidemia, and improving body weight, insulin resistance, diabetes and hypertension. In the present study, a high-fructose diet fed rat model of hypertriglyceridemia, dyslipidemia, insulin resistance and hepatic steatosis was employed to investigate the global transcriptional changes in the lipid metabolizing pathways in three insulin sensitive tissues: liver, skeletal muscle and adipose tissue in response to chronic dietary administration of NDGA. Sprague-Dawley male rats (SD) were fed a chow (control) diet, high-fructose diet (HFrD) or HFrD supplemented with NDGA (2.5 g/kg diet) for eight weeks. Dietary administration of NDGA decreased plasma levels of TG, glucose, and insulin, and attenuated hepatic TG accumulation. DNA microarray expression profiling indicated that dietary administration of NDGA upregulated the expression of certain genes involved in fatty acid oxidation and their transcription regulator, PPARα, decreased the expression of a number of lipogenic genes and relevant transcription factors, and differentially impacted the genes of fatty acid transporters, acetyl CoA synthetases, elongases, fatty acid desaturases and lipid clearance proteins in liver, skeletal muscle and adipose tissues. These findings suggest that NDGA ameliorates hypertriglyceridemia and steatosis primarily by inhibiting lipogenesis and enhancing fatty acid catabolism in three major insulin responsive tissues by altering the expression of key enzyme genes and transcription factors involved in de novo lipogenesis and fatty acid oxidation.
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影响因子：
6.5
作者：
Amemiya-Kudo, M;Shimano, H;Yamada, N
通讯作者：
Yamada, N
DOI：
10.1016/j.bpg.2014.07.008
发表时间：
2014-08-01
影响因子：
3.2
作者：
Dietrich, Peter;Hellerbrand, Claus
通讯作者：
Hellerbrand, Claus
影响因子：
3.8
作者：
Almeda-Valdes, Paloma;Cuevas-Ramos, Daniel;Aguilar-Salinas, Carlos Alberto
通讯作者：
Aguilar-Salinas, Carlos Alberto
DOI：
10.1161/atvbaha.107.151092
发表时间：
2008-04-01
影响因子：
8.7
作者：
Grundy, Scott M.
通讯作者：
Grundy, Scott M.
人类脂肪肝病：旧问题和新见解。
DOI：
10.1126/science.1204265
发表时间：
2011-06-24
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cohen JC;Horton JD;Hobbs HH
通讯作者：
Hobbs HH