Bone marrow mesenchymal stem cells of the intrauterine growth-restricted rat offspring exhibit enhanced adipogenic phenotype.
Bone marrow mesenchymal stem cells of the intrauterine growth-restricted rat offspring exhibit enhanced adipogenic phenotype.
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DOI：
10.1038/ijo.2016.157
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发表时间：
2016-11
影响因子：
4.9
通讯作者：
Rehan, V. K.
中科院分区：
文献类型：
--
作者：
Gong, M.;Antony, S.;Sakurai, R.;Liu, J.;Iacovino, M.;Rehan, V. K.
虽然宫内营养应激导致子代肥胖和代谢表型，但其细胞/分子机制仍不完全清楚，我们验证了以下假设：与对照组相比，宫内生长受限（IUGR）子代的骨髓间充质干细胞（BMSCs）表现出更高的成脂表型。一种成熟的母体食物限制（MFR）大鼠模型，即，在妊娠后半期采用50%的总体热量限制，出生后随意饮食，已知这会导致具有代谢表型的肥胖后代。分离3周龄的BMSCs，然后进行分子和功能分析。子宫内营养受限后代的BMSCs在miRNA、mRNA和蛋白水平上表现出增殖增加和脂肪形成分子谱增强，总体上调了PPARγ（miR-30 d、miR-103、PPARγ、C/EPBα、ADRP、LPL、SREBP 1），但下调了Wnt（LRP 5、LEF-1、β-catenin、ZNF 521和RUNX 2）信号传导谱。在成脂诱导后，与对照BMSC相比，已经上调的MFR BMSC的成脂谱显示出进一步增加的成脂反应。显着增强的脂肪形成的分子特征和增加的细胞增殖的MFR BMSCs表明，宫内营养应激和后代的代谢表型，包括肥胖症，提供了新的潜在的预测和治疗目标，对这些条件的IUGR后代之间可能的新的细胞/机制的联系。
Although intrauterine nutritional stress is known to result in offspring obesity and metabolic phenotype, the underlying cellular/molecular mechanisms remain incompletely understood.We tested the hypothesis that compared to the controls, the bone marrow-derived mesenchymal stem cells (BMSCs) of the intrauterine growth restricted (IUGR) offspring exhibit to a more adipogenic phenotype. A well-established rat model of maternal food restriction (MFR), i.e., 50% global caloric restriction during the later-half of pregnancy and ad libitum diet following birth that is known to result in an obese offspring with a metabolic phenotype was used. BMSCs at 3 weeks of age were isolated, and then molecularly and functionally profiled. BMSCs of the intrauterine nutritionally-restricted offspring demonstrated an increased proliferation and an enhanced adipogenic molecular profile at miRNA, mRNA and protein levels, with an overall up-regulated PPARγ (miR-30d, miR-103, PPARγ, C/EPBα, ADRP, LPL, SREBP1), but down-regulated Wnt (LRP5, LEF-1, β-catenin, ZNF521 and RUNX2) signaling profile. Following adipogenic induction, compared to the control BMSCs, the already up-regulated adipogenic profile of the MFR BMSCs, showed a further increased adipogenic response. Markedly enhanced adipogenic molecular profile and increased cell proliferation of MFR BMSCs suggest a possible novel cellular/mechanistic link between the intrauterine nutritional stress and offspring metabolic phenotype including obesity, providing new potential predictive and therapeutic targets against these conditions in the IUGR offspring.
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