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OHSU Doernbecher儿童医院研究人员研究证实，在怀孕期间孕妇高脂肪饮食和肥胖危及胎儿肝脏中的血液形成或造血干细胞系统。
西式饮食对心脏和血液循环系统的终身负担早已受到广泛关注。然而，在这项研究之前，没有人会考虑胎儿发育中造血干细胞是否可能同样容易受到产妇产前高脂饮食和/或肥胖的影响。该研究结果发表在国际著名杂志《Molecular Metabolism 分子代谢》上。
此研究结果提供了一个模型用于测试是否高脂饮食和肥胖对胎儿造血干细胞的影响可通过饮食干预来得到修复。几年前，Marks和他的同事开发了一种小鼠模型，高度模仿许多年轻女性育龄阶段食用高脂肪对胎儿造血干细胞的影响。他们后来的研究表明雌性小鼠怀孕期间营养过剩，显著减少胎小鼠肝脏的大小。
同时他们发现母体高脂饮食和肥胖显著约束胎小鼠肝脏中造血干细胞的生长和扩增，最终损害了免疫系统。
推荐原文阅读：
MolecularMetabolism:doi:10.1016/j.molmet.2014.11.001
Maternal high-fat dietand obesity compromise fetal hematopoiesis
Objective
Recent evidence indicates that the adulthematopoietic system is susceptible to diet-induced lineage skewing. It is notknown whether the developing hematopoietic system is subject to metabolicprogramming via in utero high-fat diet (HFD) exposure, an established mechanismof adult disease in several organ systems. We previously reported substantiallosses in offspring liver size with prenatal HFD. As the liver is the mainhematopoietic organ in the fetus, we asked whether the developmental expansionof the hematopoietic stem and progenitor cell (HSPC) pool is compromised byprenatal HFD and/or maternal obesity.
Methods
We used quantitative assays, progenitorcolony formation, flow cytometry, transplantation, and gene expression assayswith a series of dietary manipulations to test the effects of gestationalhigh-fat diet and maternal obesity on the day 14.5 fetal liver hematopoieticsystem.
Results
Maternal obesity, particularly when pairedwith gestational HFD, restricts physiological expansion of fetal HSPCs whilepromoting the opposing cell fate of differentiation. Importantly, these effectsare only partially ameliorated by gestational dietary adjustments for obesedams. Competitive transplantation reveals compromised repopulation andmyeloid-biased differentiation of HFD-programmed HSPCs to be a niche-dependentdefect, apparent in HFD-conditioned male recipients. Fetal HSPC deficienciescoincide with perturbations in genes regulating metabolism, immune andinflammatory processes, and stress response, along with downregulation of genescritical for hematopoietic stem cell self-renewal and activation of pathwaysregulating cell migration.
Conclusions
Our data reveal a previously unrecognizedsusceptibility to nutritional and metabolic developmental programming in thefetal HSPC compartment, which is a partially reversible andmicroenvironment-dependent defect perturbing stem and progenitor cell expansionand hematopoietic lineage commitment.
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