肝脏和胰腺细胞对早期生命营养不匹配的反应
Shubhamoy Ghosh1, Amit Ganguly1, Manal Habib2
1Division of Neonatology & Developmental Biology, Department of Pediatrics, UCLA Children's Discovery & Innovation Institute at the David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1752, USA.
Endocrinology
|January 17, 2025
概括
围产期营养不匹配导致与代谢功能障碍相关的脂肪性肝病和糖尿病,特别是在男性中. 人类素和FGF21可以通过恢复胰腺β岛功能来逆转这些影响.
科学领域:
- 代谢障碍 代谢障碍 代谢障碍
- 内分泌学 在内分泌学.
- 发育生物学是发展生物学.
背景情况:
- 围产期营养侮辱可以导致长期的代谢功能障碍.
- 宫内生长限制 (IUGR) 与产后过度营养相结合是显著的危险因素.
- 越来越多地认识到代谢性疾病发展中的基于性别的差异.
研究的目的:
- 研究将围产期营养不匹配与代谢功能障碍相关的脂肪性肝病 (MASLD) 和糖尿病相关的机制.
- 为了比较不同产后饮食对IUGR后代的影响.
- 探索性别特异的表型和分子变化.
主要方法:
- 使用了一种具有产前热量限制和IUGR的老鼠模型.
- 产后饮食包括高脂肪/高果糖 (HFhf) 或高碳水化合物.
- 在男性和女性后代中评估成人表型,肝脏基因表达和胰腺β岛功能.
主要成果:
- 与女性相比,男性表现出更大的脂肪,葡萄糖不耐受,胰岛素耐药性,高脂血症和肝硬化症.
- 男性肝脏显示甘油三合成增加和新的脂质生成基因.
- 女性的脂解,β-氧化,脂肪酸排泄和FGF21基因表达的增加. 男性的IUGR-HFhf降低了β岛屿胰岛素和人氨酸水平.
- 人类的抑制损害了葡萄糖刺激的胰岛素分泌和β-岛屿活力.
结论:
- 围产期营养不匹配,特别是在男性中,通过不同的分子路径驱动MASLD和糖尿病.
- 人类素在维护β小岛功能和预防代谢功能障碍方面发挥着至关重要的作用.
- 人类素和FGF21代表了潜在的治疗点,可以逆转围产期营养侮辱的不良代谢结果.
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