李于:SIRT1 Regulation of Energy METabolism: Attenuation of Hepatic Steatosis and Obesity
Fibroblast growth factor 21 (FGF21) is the hepatocyte-derived hormone that regulates fatty acid METabolism and has potential to treat obesity and diabetes. We recently indicate that hepatic overexpression of SIRT1 in diabetic mice attenuates hepatic steatosis and insulin resistance. However, the in vivo long-term consequence of hepatic SIRT1 ablation in liver physiology remains unknown.
We showed that hepatocyte-specific SIRT1 knockout (SIRT1 LKO) mice with the albumin Cre-loxP system exhibited a striking phenotype with greater propensity for obesity on a chow diet, characterized by increased whole body mass and fat mass, reduced energy expenditure, and unaltered food intake and physical activity. The obese phenotypes of SIRT1 LKO mice were associated with reduced hepatic and circulating levels of fasting FGF21.
Hepatic impairment of FGF21 repressed expression of key enzymes involving fatty acid oxidation such as CPT1α and MCAD, and inhibited expression of ketogenic enzymes including ACAT1, HMGCS2, HMGCL, and BDH1, thereby reducing plasma β–hydroxybutyrate levels in SIRT1 LKO mice. Moreover, transcriptional activity of a FGF21 promoter-driven luciferase reporter was stimulated by SIRT1 activators, resveratrol and SRT1720, in SIRT1+/+ MEFs, but not in SIRT1-/- MEFs.
The ability of resveratrol and SRT1720 to stimulate FGF21 protein was abolished by SIRT1 H335A inactive mutant or by nicotinamide and splitomicin in HepG2 cells. Induction of FGF21 by SIRT1 activators enhanced expression of key enzymes for fatty acid oxidation and ketogenesis.
These in vivo and in vitro findings characterize 1) hepatic SIRT1 as a master regulator of FGF21; 2) SIRT1-dependent activation of FGF21 in liver as a component for adaptive fasting response; and 3) defective hepatic SIRT1 and FGF21 signaling as a key pathological determinant of energy METabolic abnormality and obesity susceptibility.
AffyMETix芯片原理--陈巍学基因(28)
陈巍学基因这个节目,主要是为大家介绍基因组学,和临床分子诊断的最新技术进展.
今天,主要和大家谈一下著名的生物芯片公司 AffyMETrix 公司,以及它应用得最广的两种芯片:表达谱芯片、和SNP分型芯片。主要分为以下几个部分:
1.AffyMETrix 芯片的制造过程,类似半导体芯片的制造过程,是通过光蚀刻来完成的。
2.AffyMETrix 的表达谱芯片,分成传统的In Vitro Transcription 芯片和Whole Transcriptome 芯片。
3.AffyMETrix 公司的基因分型芯片,也就是SNP分型芯片有两种实验原理:新的是Axiom芯片,是基于连接反应的;而老的卡式芯片,是基于目标DNA片段与探针序列进行杂交。
4.AffyMETrix 分析表达谱的软件。
Snapshots of METalloproteins in Action
1、金属蛋白定义 2、某些惊人的反应:固碳与氧的演化、无氧碳固定术、固氮(作用)、初级代谢的分子转变、核酸代谢的分子变换、建筑分子支架 、剪裁分子支架。 3、金属反应性的生物危害性 4、金属蛋白的应用研究 5、研究金属蛋白的技术挑战和益处 6、以快照的金属蛋白
METalloproteins and Medicine
如何采取快照?为什么拍快照?我们的快照的酶的人群、核糖核酸还原酶、活性部位自由基的产生、变构调节、RNRs是重要的药物靶点;抗肿瘤、抗寄生虫和抗病毒治疗,在此一一为您讲解。
METalloproteins and the Environment
B12定位在CH3转移cfesp如何?摆动夹紧动作B12 17 Å.复杂我们守在这里 。你为什么需要140(或220)为转移甲基?在一部分,以形成一个稳定的框架,以允许这些大;构象变化是催化的关键。
Synthetic Biology & METabolic Engineering Teaching an Old Bacterium New Tricks
在第一部分,普莱瑟博士解释说,合成生物学涉及工程原理应用到生物的系统建立生物机器。在建筑这些机器的关键材料是合成DNA。合成DNA可以添加在不同的组合,以生物宿主,如细菌,把它们变成化学工厂,能生产小分子的选择。
Synthetic Biology & METabolic Engineering Teaching an Old Bacterium New Tricks
在2部分,普拉瑟介绍了她的实验室使用的设计原则设计E. coli从葡萄糖生产葡萄糖二酸。葡糖酸不在细菌中自然产生的所以,普拉瑟和她的同事们“bioprospected”从其他生物酶并在大肠杆菌中表达,构建所需的酶途径。普拉瑟走我们通过优化时序的许多步骤,酶表达的定位和水平,以产生最大的产量。
【直播】循证医学--METa分析系列课程---METa分析概述
METa分析与证据等级金字塔 METa分析,综述与系统性评价 METa分析起源与发展 METa分析流程