Maternal food restriction-induced intrauterine growth restriction in a rat model leads to sex-specific adipogenic programming.
Maternal food restriction-induced intrauterine growth restriction in a rat model leads to sex-specific adipogenic programming.
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DOI：
10.1096/fj.202000985rr
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发表时间：
2020-12
期刊：
影响因子：
--
通讯作者：
Rehan VK
中科院分区：
文献类型：
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作者：
Sreekantha S;Wang Y;Sakurai R;Liu J;Rehan VK
宫内生长受限（IUGR）会导致后代肥胖。在一个与孕期母体食物受限（MFR）相关的IUGR大鼠模型中，骨髓干细胞显示出增强的成脂编程；然而，IUGR对白色脂肪组织（WAT）祖细胞的影响尚不清楚。在此，通过mRNA和功能分析，我们确定了从出生后第1天和第21天的幼崽中分离出的WAT祖细胞的性别特异性成脂编程。在出生后第1天，MFR雄性和雌性的前脂肪细胞中PPARγ和Pref - 1的表达均显著下调；然而，在出生后第21天，MFR雄性的前脂肪细胞中这些基因表达上调。即使在成脂诱导后，出生后第1天的MFR雄性和雌性脂肪细胞均表现出较低的PPARγ、ADRP和脂联素水平；然而，在出生后第21天，MFR雄性脂肪细胞中这些基因的表达呈上升趋势。一个成脂特异性RT - PCR芯片显示，MFR雄性脂肪细胞被编程为比雌性具有更强的成脂倾向。最后，血清性激素以及脂肪细胞雌激素/睾酮受体表达谱为IUGR后代中性别特异性成脂编程的潜在机制提供了初步见解。总之，IUGR使雄性WAT前脂肪细胞具有更大的成脂潜能。尽管在出生后第1天就可检测到MFR后成脂编程的改变，但在出生后第21天变化更为显著，这表明出生后营养在促进IUGR后代性别特异性成脂编程中具有潜在作用。
Intrauterine growth restriction (IUGR) leads to offspring obesity. In a maternal food restriction (MFR) during pregnancy-related IUGR rat model, bone marrow stem cells showed enhanced adipogenic programming; however, the effect of IUGR on white adipose tissue (WAT) progenitors is unknown. Here, by mRNA and functional profiling, we determined sex-specific adipogenic programming of WAT progenitors isolated from pups on postnatal day (PND) 1 and 21. On PND1, PPARγ and Pref-1 expression was significantly downregulated in preadipocytes of both MFR males and females; however, at PND21, preadipocytes of MFR males showed upregulation in these genes. Even following adipogenic induction, both male and female MFR adipocytes exhibited lower PPARγ, ADRP, and adiponectin levels at PND1; however, at PND21 MFR male adipocytes showed an upward trend in the expression of these genes. An adipogenesis-specific RT-PCR array showed that male MFR adipocytes were programmed to exhibit stronger adipogenic propensity than females. Lastly, serum sex hormone and adipocyte estrogen/testosterone receptor expression profiles provide preliminary insights into the possible mechanism underlying sex-specific adipogenic programming in the IUGR offspring. In summary, IUGR programs WAT preadipocytes to a greater adipogenic potential in males. Although the altered adipogenic programming following MFR was detectable at PND1, the changes were more pronounced at PND21, suggesting a potential role of postnatal nutrition in facilitating the sex-specific adipogenic programming in the IUGR offspring.