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

我们研究了结缔组织生长因子、emerin 和 calpain 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，并且在初始阶段，这 3 个分子的 mRNA 表达是由地塞米松混合物诱导的。脂肪细胞从 3T3-L1 细胞分化而来，并且它们在基因的 5' 侧翼区域具有人类直系同源物以及糖皮质激素反应元件。每个mRNA表达中的RNA干扰未能改变脂肪细胞的分化，这表明这些分子，至少是每个单个分子，对于脂肪细胞分化的初始步骤不是必需的。 接下来，代谢综合征（MetS）和CCAAT之间的关联/增强子结合蛋白δ（C/EBPδ）在172名健康检查者的知情同意下进行了研究。在使用C/EBPδ敲除小鼠的研究中报道了C/EBPδ mRNA的诱导。 gluc … More 在 3T3-L1 细胞的最初脂肪细胞分化过程中，皮质激素对于内脏肥胖至关重要。我们的结果首次表明，SNP rs15955 中的基因型 C/T 在血脂异常以及糖耐量受损 (IGT) 人群中更为常见。此外，最近报道神经肽 Y (NPY)/NPY 2 型受体 (NPY2R) 通路与高脂肪和蔗糖饮食在某些压力下诱导内脏肥胖并刺激糖皮质激素分泌，因此，我们在 317 人中测试了 MetS（IDF 亚洲标准）与 NPY2R 基因 SNP 的 5' 侧翼区域之间的关联。对于在知情同意后参与本研究的健康检查，SNP rs6857715 中的基因型'17 在 MetS 和 IGT 基因型中更为普遍。 SNP rs6857530 中的 AA 在 IGT 中更为普遍，需要对这些 SNP 区域的转录控制进行进一步的功能研究，以制定 MetS 的预防策略和药物发现。

项目成果

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

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

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

Difference in the frequency of polymorphism in the growth hormone receptor gene between Japanese and Caucasian populations

日本人和白人之间生长激素受体基因多态性频率的差异

• 发表时间: 2006
• 作者: Iida;K.;Takahashi;Y.;Kaji;H.;Okimura;Y.;Nose;O.;Chihara;K.
• 通讯作者: K.