Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Cell Rep. 2023 Apr 25;42(4):112393. doi: 10.1016/j.celrep.2023.112393. Epub 2023 Apr 13.
Maternal overnutrition increases inflammatory and metabolic disease risk in postnatal offspring. This constitutes a major public health concern due to increasing prevalence of these diseases, yet mechanisms remain unclear. Here, using nonhuman primate models, we show that maternal Western-style diet (mWSD) exposure is associated with persistent pro-inflammatory phenotypes at the transcriptional, metabolic, and functional levels in bone marrow-derived macrophages (BMDMs) from 3-year-old juvenile offspring and in hematopoietic stem and progenitor cells (HSPCs) from fetal and juvenile bone marrow and fetal liver. mWSD exposure is also associated with increased oleic acid in fetal and juvenile bone marrow and fetal liver. Assay for transposase-accessible chromatin with sequencing (ATAC-seq) profiling of HSPCs and BMDMs from mWSD-exposed juveniles supports a model in which HSPCs transmit pro-inflammatory memory to myeloid cells beginning in utero. These findings show that maternal diet alters long-term immune cell developmental programming in HSPCs with proposed consequences for chronic diseases featuring altered immune/inflammatory activation across the lifespan.
母体营养过剩会增加后代出生后患炎症性和代谢性疾病的风险。由于这些疾病的患病率不断上升，这构成了一个主要的公共卫生关注点，但其中的机制仍不清楚。在这里，我们使用非人类灵长类动物模型表明，母体西式饮食（mWSD）暴露与 3 岁幼崽骨髓来源的巨噬细胞（BMDMs）和胎儿及幼崽骨髓和胎肝造血干细胞和祖细胞（HSPCs）中在转录、代谢和功能水平上持续存在的促炎表型有关。mWSD 暴露还与胎肝和幼崽骨髓中的油酸含量增加有关。对来自 mWSD 暴露幼崽的 HSPCs 和 BMDMs 的转座酶可及染色质测序（ATAC-seq）分析表明，HSPCs 从宫内开始就将促炎记忆传递给髓系细胞。这些发现表明，母体饮食会改变 HSPC 中免疫细胞的长期发育编程，这可能导致终生存在免疫/炎症激活改变的慢性疾病。
