Scientists from the Cincinnati Children’s Hospital Medical Center, CCHMC, USA, have found a negative obesity effect on the long-term health of hematopoietic stem cells in mice. The results of the study were published on December 27, 2017 in The Journal of Experimental Medicine.
A study, conducted by specialists from the Cincinnati Children’s Institute of Cancer and Blood Diseases, performed on genetic models of mice with obesity, showed long-term durable and damaging changes in hematopoietic stem cells – the blood-making factory in our bodies.
“There is now an understanding that the blood stem cell compartment is made up of numerous cell subsets”, – said Damien Reynaud, PhD, the study’s principal investigator.
“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.”
Studies show that age and problematic ecology can reduce the healthy variety of hematopoietic cells in the body, but the mechanisms of this process are still not fully understood. According to Reynaud and his collaborators , this can cause deviations in the maturation of blood cells, leading to the appearance of myeloid cells and the development of leukemia.
Reynaud and co-authors, including the first author of the article, Jung-Mi Lee, demonstrated that the stresses associated with obesity change the cellular architecture of the compartment of hematopoietic stem cells and reduce its long-term functional fitness.
Tests in obese mice showed that these effects are progressive and some of the negative manifestations persist even after the researchers normalized the weight of the animal with a controlled diet.
Raynaud’s team reports that these alterations of the body’s blood-making system appear to be linked to over-expression of a transcription factor Gfi1, a regulatory gene that controls other genes. Researchers show that oxidative stress in the body caused by obesity leads to overexpression of Gfi1.
In this case, there is a lasting alteration of hematopoietic stem cell compartment and molecular mayhem may ensue. Researchers say their work also provides groundwork to investigate of lifestyle choices, including dieting, that can have a lasting impact on blood formation and may contribute to the development of blood cancer.
Hematopoietic stem cells are an important tool for the treatment of leukemia and other blood diseases. The study raises questions about the use of hematopoietic stem cells isolated from obese people in therapeutic transplant procedures
“Little is known about how obesity in marrow donors could affect the quality of the hematopoietic stem cell compartment”, – Reynaud explains. “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.”