Obesity has been associated with the onset of disease, and researchers have now found that the health of hematopoietic stem cells, which make blood, is negatively affected by obesity. Reported in the Journal of Experimental Medicine, the study relied primarily on mouse models of genetically-induced obesity to demonstrate the long-term, harmful impact it has on the hematopoietic stem cell compartment. Our bodies rely on that compartment to generate blood.
"There is now an understanding that the blood stem cell compartment is made up of numerous cell subsets," explained the principal investigator of the work, Damien Reynaud, Ph.D. "Keeping this compartment healthy is essential to human health. This includes maintaining the diverse pool of blood-making stem cells (hematopoietic stem cells) needed to produce blood cells the body needs to function properly."
It seems that the stress of age and environmental factors can reduce diversity among the cells that synthesize our blood. Blood cell formation can then skew toward myeloid cells, which may increase the risk that cells can become pre-leukemic, suggested Reynaud and his collaborators.
The research team showed that the architecture of the hematopoietic stem cell compartment is changed by stress related to obesity, and the overall impact is a reduction in the functionality of the compartment. Tests in mice have indicated that these effects are progressive and cause dysfunction that can persist even when the weight of the animal returns to normal by dieting.
The scientists wanted to learn more about the mechanism underlying this phenomenon. They found it may be connected to the increased expression of the Gfi1 gene. The gene is a transcription factor, which regulates the expression of other genes. In the obese state, there are oxidative stresses in the body that drive increased expression of Gfi1. That in turn, results in lasting alterations in the hematopoietic stem cell compartment, and subsequent molecular disorders.
This research may lay the groundwork for showing how choices we make about diet and lifestyle can cause enduring impacts to the formation of blood and the risk of developing blood cancer. Importantly, hematopoietic stem cells are often used in therapeutics for leukemia and other diseases of the blood. This work indicates that obese people may not be the best donors of stem cells for use in these kinds of procedures.
"Little is known about how obesity in marrow donors could affect the quality of the hematopoietic stem cell compartment," Reynaud explained. "We want to better understand the molecular alterations in obesity to predict potential risks associated with the therapeutic use of stem cells isolated from obese donors."