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鼠标骨肌和脂肪组织中的替代拼接景观:间歇性禁食和运动的影响

Jasmin Gaugel¹, Markus Jähnert², Alexander Neumann³

¹Research Group Nutrigenomics of Obesity and Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; German Center for Diabetes Research (DZD), München-Neuherberg, Germany; Research Group Molecular and Clinical Life Science of Metabolic Diseases, Faculty of Health Sciences Brandenburg, University of Potsdam, Brandenburg, Germany.

The Journal of nutritional biochemistry

|December 26, 2024

概括

禁食和运动等生活方式干预会诱导小鼠组织中轻微的替代拼接变化. 虽然通常很小,但肌肉和脂肪组织中的这些拼接变化可能会影响与糖尿病相关的基因.

科学领域:

分子生物学分子生物学
基因组学就是基因组学.
代谢研究研究代谢研究

背景情况:

替代拼接使蛋白质生产多样化,但异常拼接与疾病有关.
错误拼接在2型糖尿病中的作用及其通过生活方式干预的可逆性仍然不清楚.

研究的目的:

在小鼠模型中调查替代拼接变化的程度,以应对生活方式干预 (间歇性禁食和运动).
确定这些拼接变化是否有助于胰岛素抵抗和2型糖尿病.
通过改变生活方式来评估扭转拼接缺陷的潜力.

主要方法:

在骨肌和脂肪组织上进行了RNA测序,来自NZO小鼠 (易患糖尿病) 进行间歇性禁食和C57BL/6J小鼠 (健康) 进行运动.
使用Whippet和rMATS分析了不同的替代拼接事件.
基因表达和表型参数与拼接变化相关.

主要成果:

饮食和运动干预都诱导了可比的拼接变化水平,骨肌肉比脂肪组织更具灵活性.
拼接变化通常是轻微的 (最大PSI差异为67%),这表明在整体生活方式适应中起的作用很小.
内部保留影响了与表型参数相关的基因 (例如,Eno2,Pan2). 间歇性禁食影响了Mlxipl拼接 (ChREBP),影响了葡萄糖传感.
间歇性禁食和运动诱导了已知与糖尿病相关的GWAS基因 (例如Abcc8,Ifnar2,Smarcad1) 的替代拼接.

结论:

替代拼接在小鼠的肌肉和脂肪组织的生活方式诱导的适应中起着相对较小的作用.
特定的拼接事件,如内质保留和糖尿病相关基因的变化,可能具有代谢相关性.
生活方式干预可以调节可能影响糖尿病病理生理学的替代拼接.

关键词:

另一个替代拼接.生活方式干预措施肥胖问题肥胖问题骨架肌肉是一个骨肌肉.2 型糖尿病 2 型糖尿病白色脂肪组织的脂肪组织.

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