Identification of glucocorticoid target genes involved in visceral obesity

由于糖皮质激素对脂肪细胞的分化非常重要，并且在3T3-L1细胞向脂肪细胞分化的初始阶段，这三个分子的mRNA表达是在地塞米松的诱导下被地塞米松诱导的，并且它们在基因的5‘-侧翼区域具有人类同源基因和糖皮质激素反应元件，因此我们研究了结缔组织生长因子、Emerin和calain 1是否是脂肪细胞分化的起始步骤所必需的。其次，在172名健康体检者知情同意后，对代谢综合征(METS)和CCAAT/增强子结合蛋白δ(C/EBPδ)的相关性进行了研究。在利用C/eBPδ基因敲除小鼠的研究中，已经报道了Glucδ诱导C/eBP…基因的表达在3T3-L1细胞向脂肪细胞分化的初始阶段，更多的皮质激素是内脏肥胖的关键。我们的结果首次表明，SNP rs15955的C/T基因型在糖耐量低减(IGT)和血脂异常中更为常见。此外，神经肽Y(NPY)/NPY 2型受体(NPY2R)途径最近被报道参与了高脂和蔗糖饮食诱导的内脏肥胖，在一定的应激状态下，糖皮质激素的分泌受到刺激。因此，我们在亚洲人群中检验了Mets(IDF Asia Criteria)与NPY2R基因SNPs 5‘侧翼区的相关性，这些SNPs具有较高的等位基因频率。在317名健康体检者中，在知情同意后，SNP rs6857715的‘17基因型在蛋氨酸和糖耐量低减患者中更为常见。SNP rs6857530的AA基因型在糖耐量低减患者中更常见。这些SNP区域转录调控的进一步功能研究将被用于制定蛋氨酸代谢综合征的预防策略和药物开发。

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