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Infant Mesenchymal Stem Cell Insulin Action is Associated With Maternal Plasma Free Fatty Acids, Independent of Obesity Status: The Healthy Start Study
Diabetes ( IF 7.7 ) Pub Date : 2022-05-27 , DOI: 10.2337/db21-0812
Alec B Chaves 1, 2 , Donghai Zheng 1, 2 , Jonathan A Johnson 1, 2 , Bryan C Bergman 3 , Zachary W Patinkin 4 , Vincent Zaegel 5 , Ericka M Biagioni 1, 2 , Polina Krassovskaia 1, 2 , Nicholas T Broskey 1, 2 , Linda E May 1, 2 , Dana Dabelea 5, 6, 7 , Joseph A Houmard 1, 2 , Kristen E Boyle 5, 7
Affiliation  

Preclinical rodent and non-human primate models investigating maternal obesity have highlighted the importance of the intrauterine environment for development of insulin resistance in the offspring; however, it remains unclear if these findings can be translated to humans. To investigate possible intrauterine effects in humans, we isolated mesenchymal stem cells (MSCs) from the umbilical cord tissue of infants born to mothers of normal weight (NW) or mothers with obesity (Ob). Insulin stimulated glycogen storage was determined in MSCs undergoing myogenesis in vitro. And there was no difference in insulin action based on maternal obesity. However, maternal free fatty acid concentration, cord leptin, and intracellular triglyceride content were positively correlated with insulin action. Furthermore, MSCs from offspring born to mothers with elevated FFA displayed elevated activation of the mTOR signaling pathway. Taken together, these data suggest that infants born to mothers with elevated lipid availability have greater insulin action in MSC, which may indicate upregulation of growth and lipid storage pathways during periods of maternal overnutrition.

中文翻译:

婴儿间充质干细胞胰岛素作用与母体血浆游离脂肪酸相关,与肥胖状况无关:健康开始研究

研究孕产妇肥胖的临床前啮齿动物和非人类灵长类动物模型强调了子宫内环境对后代胰岛素抵抗发展的重要性;然而,目前尚不清楚这些发现是否可以转化为人类。为了研究对人类可能的宫内效应,我们从正常体重母亲 (NW) 或肥胖母亲 (Ob) 所生婴儿的脐带组织中分离了间充质干细胞 (MSC)。在体外进行肌生成的 MSC 中测定了胰岛素刺激的糖原储存。胰岛素作用并没有因母亲肥胖而产生差异。然而,母体游离脂肪酸浓度、脐带瘦素和细胞内甘油三酯含量与胰岛素作用呈正相关。此外,FFA 升高的母亲所生后代的 MSC 表现出 mTOR 信号通路的激活升高。总而言之,这些数据表明,脂质可用性较高的母亲所生的婴儿在间充质干细胞中具有更强的胰岛素作用,这可能表明在母亲营养过剩期间生长和脂质储存途径的上调。
更新日期:2022-05-27
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