Scientists at the Cincinnati Children’s Cancer and Blood Diseases Institute have been researching the effect of obesity on hematopoietic stem cells – stem cells that differentiate into red and white blood cells.
The researchers have shown obesity can have a major negative effect on the hematopoietic stem cell compartment, the part of the body where blood cells are formed. Those changes can seriously affect long term health and could raise the risk of developing blood cancer.
The study, performed on genetic models of obese mice, showed that stresses related to obesity alter the architecture of the hematopoietic stem cell compartment, dramatically reducing long term functional fitness. Further, those changes were shown to be irreversible in many cases. When the mice were returned to normal weight levels, the harmful effect of obesity on hematopoietic stem cells persisted.
The researchers showed obesity results in changes to a gene called Gfi1, which regulates expression of other genes. The over expression of this gene causes lasting changes that persist even when weight is brought back to normal, healthy levels.
In the paper, the researchers explain “The oxidative stress induced by obesity dysregulates the expression of the transcription factor Gfi1 and that increased Gfi1 expression is required for the abnormal HSC function induced by obesity.”
The study suggests that lifestyle choices can have a major impact on blood formation, and could potentially increase the risk of patients suffering from leukemia. Further, since hematopoietic stem cells are used in the treatment of leukemia and other blood diseases, the study raises important questions about where hematopoietic stem cells are harvested, suggesting hematopoietic stem cells should not be extracted from obese donors.
The researchers explain that this is an important area for further research. Principal investigator for the study, Damien Reynaud, PhD, said “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.”
The paper – Obesity alters the long-term fitness of the hematopoietic stem cell compartment through modulation of Gfi1 expression – was recently published in the Journal of Experimental Medicine.