Identification of glucocorticoid target genes involved in visceral obesity

内脏肥胖相关糖皮质激素靶基因的鉴定

• 批准号: 18590997
• 负责人: KAJI Hidesuke
• 金额: $ 2.46万
• 依托单位: University of Hyogo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590997/
• 关键词: adipocyte; glucocorticoid; RNA interference (RNAi); metabolic syndrome (MetS); single nuculeotide polymorphism (SNP); CCAAT; enhancer binding protein 8 (C; EBPδ); neuropeptide Y (NPY); NPY type 2 receptor (NPY2R); ニューロペプチドY2受容体; メタボリックシンドローム

We investigated to clarify whether connective tissue growth factor, emerin, and calpain 1 are essential for the initial step of adipocyte differentiation, since glucocorticoid is very important for adipocyte differentiation, and mRNA expressions of these 3 molecules are induced by cocktail with dexamethasone during the initial adipocyte differentiation from 3T3-L1 cells, and they have their human ortholog as well as glucocorticoid responsive element on their 5'-flanking region of the gene. The RNA interference in each mRNA expression failed to change the adipocyte differentiation, suggesting that these molecules, at least by each single molecule, are not essential for the initial step of the adipocyte differentiation.Next, the association between metabolic syndrome (MetS) and CCAAT/enhancer binding protein δ (C/EBPδ) was investigated after informed consent in 172 persons for health checkup. It has been reported in the study using C/EBPδ knockout mouse that C/EBPδ mRNA induction by gluc … More ocorticoid during the initial adipocyte differentiation from 3T3-L1 cells is essential for visceral obesity. Our result indicated for the first time that genotype C/T in SNP rs15955 was more prevalent in dyslipidemia as well as impaired glucose tolerance (IGT) among phenotypes of MetS.Furthermore, neuropeptide Y (NPY)/NPY type 2 receptor (NPY2R) pathway is recently reported to be involved in high fat and sucrose diet-induced visceral obesity under certain stresses with stimulated glucocorticoid secretion. Therefore, we tested the association between MetS (IDF Asia criteria) and the 5'-flanking region of NPY2R gene SNPs with high minor allele frequency in Asian population. In 317 persons for health checkup participated in this study after informed consent, genotype '17 in SNP rs6857715 was more prevalent in MetS and IGT. Genotype AA in SNP rs6857530 was more prevalent in IGT. Further functional studies of the transcriptional control of these SNP regions will be required for the development of prevention strategy and drug discovery for MetS. Less

我们研究以澄清结缔组织生长因子、Emerin和钙蛋白酶1是否对于脂肪细胞分化的初始步骤至关重要，因为糖皮质激素对于脂肪细胞分化非常重要，并且这3种分子的mRNA表达在初始脂肪细胞分化过程中通过与地塞米松的混合物诱导。3 T3-L1细胞，并且它们在其基因的5 ′-侧翼区域上具有它们的人类直系同源物以及糖皮质激素应答元件。在知情同意的情况下，对172名健康体检者进行代谢综合征（MetS）与CCAAT/增强子结合蛋白δ（C/EBPδ）的相关性研究。在C/EBPδ基因敲除小鼠的研究中，有报道表明，GluC对C/EBPδ mRNA的诱导作用与C/EBPδ基因敲除小鼠的C/EBPδ基因敲除有关。 ...更多信息 在3 T3-L1细胞向脂肪细胞分化过程中，皮质激素的作用是内脏型肥胖的关键。本研究结果首次表明，在代谢综合征的表型中，rs 15955位点C/T基因型在血脂异常和糖耐量异常（IGT）中更常见。此外，神经肽Y（NPY）/神经肽Y 2型受体（NPY 2 R）通路最近被报道参与了高脂和蔗糖饮食诱导的内脏型肥胖在一定应激条件下刺激糖皮质激素分泌的过程。因此，我们检测了MetS（IDF亚洲标准）与亚洲人群中具有高次要等位基因频率的NPY 2 R基因SNPs的5 '侧翼区之间的关联。在知情同意后参加本研究的317名健康体检者中，SNP rs6857715的“17”基因型在MetS和IGT中的发生率较高。SNP rs6857530中AA基因型在IGT中更常见。这些SNP区域的转录调控的进一步功能研究将需要用于MetS的预防策略和药物发现的发展。少

项目成果

Genetic variations at the CCAAT/Enhancer-binding protein δ are associated with metabolic phenotypes in the Japanese population

CCAAT/增强子结合蛋白 δ 的遗传变异与日本人群的代谢表型相关

• 发表时间: 2008
• 期刊: Metabolic Syndrome and Related Disorders 6
• 作者: Kaji H;Fukano C;imura Y Takiguchi E;anida K
• 通讯作者: anida K

The N131S mutation in von Hippel-Lindau gene in a Japanese family with pheochromocytoma and hemangioblastomas.

日本嗜铬细胞瘤和血管母细胞瘤家系中 von Hippel-Lindau 基因的 N131S 突变。

• 发表时间: 2006
• 期刊: Endocrine Journal 53
• 作者: Imanaka M;Iida K;Takahashi K;Tsuji K;Nishikawa;Fukaoka H;Takeno R;Takahashi Y;Okimura Y;Kaji H;Chihara K
• 通讯作者: Chihara K

スプライシング異常が確認できたGitelman症候群の1例

剪接异常Gitelman综合征1例

• 发表时间: 2008
• 作者: 飯田 啓二、野津 寛大、高橋 裕、加治 秀介(5/8)千原 和夫;他
• 通讯作者: 他

A novel mutation in the von Hippel-Lindau tumor suppressor gene identified in a Japanese family with pheochromocytoma and hepatic hemangioma

在一个患有嗜铬细胞瘤和肝血管瘤的日本家族中发现了 von Hippel-Lindau 肿瘤抑制基因的新突变

• 发表时间: 2006
• 期刊: Intern Med 45・5
• 作者: Dai;G;Yamamoto D;Imanaka M;Takahashi K
• 通讯作者: Takahashi K

McCune-Albright Syndrome with Acromegaly and Fibrous Dysplasia Associated with the GNAS Gene Mutation Identified by Sensitive PNA-clamping Method.

敏感 PNA 钳位法鉴定出与 GNAS 基因突变相关的伴有肢端肥大症和纤维发育不良的 McCune-Albright 综合征。

• 发表时间: 2007
• 期刊: Internal Medicine 46
• 作者: Kentner AC;et al.;Mari Imanaka
• 通讯作者: Mari Imanaka