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High-fat diet, obesity during pregnancy harms stem cells in developing foetus.

Researchers from the OHSU Doernbecher Children’s Hospital reveal a high-fat diet and obesity during pregnancy compromise the blood-forming, or hematopoietic, stem cell system in the fetal liver responsible for creating and sustaining lifelong blood and immune system function.

The life-long burden of a western-style diet on the heart and circulatory system have long been appreciated. However, prior to this study, no one had considered whether the developing blood stem cells might be similarly vulnerable to prenatal high-fat diet and/or maternal obesity. The opensource study is published in the journal Molecular Metabolism.

The team state that the results offer a model for testing whether the effects of a high-fat diet and obesity can be repaired through dietary intervention, a key question when extrapolating this data to human populations.

Several years ago, the team developed a mouse model that closely mimics the high-fat, high-simple-sugar diet currently consumed by many young women of childbearing age. Their subsequent research demonstrated that maternal overnutrition in mice significantly reduced the size of the fetal liver.

In the current study the team discovered that the complex changes that occur as a result of maternal high-fat diet and obesity put significant constraints on the growth and expansion of blood stem cells in the fetal liver, which ultimately compromises the developing immune system.

In light of the spreading western-style, high-fat diet and accompanying obesity epidemic, the team summise that this study highlights the need to better understand the previous unrecognized susceptibility of the stem and progenitor cell system.  These findings may provide broad context for the rise in immune disease and allergic disposition in children.

Source:  Oregon Health & Science University

Differential expression of transcripts in HFD versus control fetal livers. (A) Heatmap visualization of differentially expressed* (DE) transcripts between high-fat and control diet programmed, male, 15 ± 0.5 dpc fetal liver cells, as analyzed by RNA-seq. Transcripts with significant fold changes, based on both fold change and FDR adjusted P-value threshold, are shown in the heat map. Gene names are indicated to the right of the heat map and cohort is shown at the bottom. Red = upregulation, green = downregulation. Dendrogram indicates sample clustering. *DE genes defined as having an FC >1.5 and FDR <0.05 in both the common and tagwise dispersion estimate analysis. Maternal high-fat diet and obesity compromise fetal hematopoiesis. Marks et al 2014.

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