Maternal high-fat diet and obesity compromise fetal hematopoiesis.
Maternal high-fat diet and obesity compromise fetal hematopoiesis.
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DOI：
10.1016/j.molmet.2014.11.001
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发表时间：
2015-01
影响因子：
8.1
通讯作者：
Marks DL
中科院分区：
文献类型：
--
作者：
Kamimae-Lanning AN;Krasnow SM;Goloviznina NA;Zhu X;Roth-Carter QR;Levasseur PR;Jeng S;McWeeney SK;Kurre P;Marks DL
最近的证据表明，成人造血系统容易受到饮食诱导的谱系偏斜。尚不清楚发育中的造血系统是否通过宫内高脂饮食（HFD）暴露进行代谢编程，这是几个器官系统中成人疾病的既定机制。我们先前报道了产前HFD的后代肝脏大小的实质性损失。由于肝脏是胎儿的主要造血器官，我们询问造血干细胞和祖细胞（HSPC）库的发育扩增是否受到产前HFD和/或母体肥胖的影响。我们使用定量分析、祖细胞集落形成、流式细胞术、移植和基因表达分析以及一系列饮食操作来测试妊娠期高脂饮食和母体肥胖对14.5天胎肝造血系统的影响。母体肥胖，特别是当与妊娠HFD配对时，限制胎儿HSPC的生理扩增，同时促进分化的相反细胞命运。重要的是，这些影响只是部分改善了妊娠期饮食调整肥胖母鼠。竞争性移植揭示了HFD程序化HSPCs的受损再增殖和骨髓偏向分化是一种生态位依赖性缺陷，在HFD调节的男性受体中很明显。胎儿HSPC缺陷与调节代谢、免疫和炎症过程以及应激反应的基因的扰动一致，沿着对造血干细胞自我更新和调节细胞迁移的途径的激活至关重要的基因的下调。我们的数据揭示了先前未被认识到的胎儿HSPC隔室中营养和代谢发育编程的易感性，这是一种部分可逆的和微环境依赖性的缺陷，干扰干细胞和祖细胞扩增和造血谱系定型。
Recent evidence indicates that the adult hematopoietic system is susceptible to diet-induced lineage skewing. It is not known whether the developing hematopoietic system is subject to metabolic programming via in utero high-fat diet (HFD) exposure, an established mechanism of adult disease in several organ systems. We previously reported substantial losses in offspring liver size with prenatal HFD. As the liver is the main hematopoietic organ in the fetus, we asked whether the developmental expansion of the hematopoietic stem and progenitor cell (HSPC) pool is compromised by prenatal HFD and/or maternal obesity. We used quantitative assays, progenitor colony formation, flow cytometry, transplantation, and gene expression assays with a series of dietary manipulations to test the effects of gestational high-fat diet and maternal obesity on the day 14.5 fetal liver hematopoietic system. Maternal obesity, particularly when paired with gestational HFD, restricts physiological expansion of fetal HSPCs while promoting the opposing cell fate of differentiation. Importantly, these effects are only partially ameliorated by gestational dietary adjustments for obese dams. Competitive transplantation reveals compromised repopulation and myeloid-biased differentiation of HFD-programmed HSPCs to be a niche-dependent defect, apparent in HFD-conditioned male recipients. Fetal HSPC deficiencies coincide with perturbations in genes regulating metabolism, immune and inflammatory processes, and stress response, along with downregulation of genes critical for hematopoietic stem cell self-renewal and activation of pathways regulating cell migration. Our data reveal a previously unrecognized susceptibility to nutritional and metabolic developmental programming in the fetal HSPC compartment, which is a partially reversible and microenvironment-dependent defect perturbing stem and progenitor cell expansion and hematopoietic lineage commitment.
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影响因子：
3.7
作者：
Adler BJ;Green DE;Pagnotti GM;Chan ME;Rubin CT
通讯作者：
Rubin CT
影响因子：
3.2
作者：
Fisher RE;Steele M;Karrow NA
通讯作者：
Karrow NA
DOI：
10.1152/ajpregu.00310.2010
发表时间：
2010-09-01
影响因子：
2.8
作者：
Heerwagen, Margaret J. R.;Miller, Melissa R.;Friedman, Jacob E.
通讯作者：
Friedman, Jacob E.
影响因子：
15.9
作者：
Kollet, O;Shivtiel, S;Lapidot, T
通讯作者：
Lapidot, T
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y