肥胖症中的内脏脂肪细胞代谢功能障碍与甲状腺激素受体的染色质可访问性改变有关
Hao Zhu1, Ji-Ru Zhang2, Zhen-Wu Ma3
1Division of Endocrinology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China; Division of Geriatric Endocrinology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China.
由于甲状腺激素受体信号的改变,肥胖会损害内脏脂肪组织 (VAT) 的功能. STAT5B被确定为这种干扰的关键因素,为肥胖提供了潜在的治疗点.
科学领域:
- 内分泌学 在内分泌学.
- 代谢研究研究 代谢研究
- 分子生物学分子生物学
背景情况:
- 内脏脂肪组织 (VAT) 在代谢平衡中起着至关重要的作用.
- 肥胖与增值税功能障碍有关,有助于代谢疾病.
- 导致肥胖的增值税功能障碍的精确分子机制尚不完全理解.
研究的目的:
- 为了调查肥胖期间增值税的变化.
- 确定导致肥胖的增值税功能障碍的分子机制.
- 探索甲状腺激素信号和STAT5B在与肥胖相关的增值税功能障碍中的作用.
主要方法:
- 从正常体重和肥胖个体获得的人类增值税样本的组织学分析.
- RNA测序 (RNA-seq) 和ATAC测序 (ATAC-seq) 用于分析基因表达和染色体可访问性.
- 在体外细胞实验中,染色体免疫沉 (CHIP) 试验和RNA干扰用于阐明分子通路.
主要成果:
- 肥胖的VAT中差异表达的基因在脂肪细胞代谢功能途径中得到丰富.
- 甲状腺激素受体结合点,包括STAT5B,在这些基因的可访问的染色体区域中发现.
- 肥胖症的特征是通过甲状腺激素受体α (THRa) 通过三甲状腺激素 (T3) 减少STAT5B的激活.
- 证实STAT5B是维持增值税代谢功能的关键转录因子.
结论:
- 肥胖症中增值税代谢功能受损与甲状腺激素受体可访问性的改变有关.
- 在肥胖症中,STAT5B是甲状腺脂肪信号通路中断的中心转录因子.
- 针对STAT5B可能是一个有前途的治疗策略,用于改善与肥胖相关的代谢功能障碍.
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