in the bone marrow
Hematopoietic stem cells
Obesity can affect the long-term health of hematopoietic stem cells (HSCs), according to research published in the Journal of Experimental Medicine.
Conducted largely in models of obese mice, the research showed that obesity causes durable and harmful changes to the HSC compartment.
“Keeping this compartment healthy is essential to human health,” said study author Damien Reynaud, PhD, of Cincinnati Children’s Hospital Medical Center in Ohio.
“This includes maintaining the diverse pool of [HSCs] needed to produce blood cells the body needs to function properly.”
Although still poorly understood, research is showing that age and environmental stresses can lessen the healthy diversity of cells in the hematopoietic system.
This can include skewing blood cell formation toward myeloid cells and possibly promoting pre-leukemic fates, according to Dr Reynaud and his colleagues.
With the current study, the team found that obesity-related stresses alter the cellular architecture of the HSC compartment and reduce its long-term functional fitness.
Tests in obese mice showed these effects were progressive. And some of the harmful manifestations persisted even after the researchers normalized the animals’ weight through dietary controls.
These alterations of the hematopoietic system appear to be linked to overexpression of the transcription factor Gfi1.
The researchers found that oxidative stresses in the body caused by obesity drive overexpression of Gfi1. When this happens, it produces a lasting alteration of the HSC compartment.
The researchers said their study provides groundwork to investigate how lifestyle choices, such as diet, can durably impact blood formation and may contribute to the development of blood cancers.
The study also raises questions about the use of HSCs isolated from obese transplant donors.
“Little is known about how obesity in marrow donors could affect the quality of the hematopoietic stem cell compartment,” Dr 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.”
