Excess Fat Tissue Leaves Lasting Damage to Stem Cells, Even if Lost


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There is a fair amount of evidence from epidemiological studies to suggest that carrying excess visceral fat tissue will cause lasting damage to bodily systems even after that fat is lost. The longer it is there, and the more it there was, the worse off you are. You might recall a study that found lifetime maximum weight to be a better predictor of later age-related mortality than other measures, for example, implying that some forms of consequence linger even if the weight is lost. The study here identifies one possible mechanism to explain this sort of outcome; the authors find a lasting impact on the stem cell populations responsible for generating the cells of the immune system and other parts of the blood supply.

Obesity continues to weigh on the blood-forming stem cell compartment, altering the balance of the cell types produced there, even after the body sheds excess weight. Under the stress of obesity, hematopoietic stem cells (HSCs) begin to overexpress a regulatory gene that tilts blood production toward myeloid cells, and may even promote preleukemic fates. This shift in gene expression, which worsens over time, results in lasting dysregulation, even if HSCs are transplanted into a normal environment.

Although these findings come from a study that relied on a mouse model of obesity, they raise questions about the use of HSCs 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. 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 research team traced the dysregulation of the HSC compartment to altered expression of Gfi1, a transcription factor. "Mechanistically, we establish that 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. These results demonstrate that obesity produces durable changes in HSC function and phenotype and that elevation of Gfi1 expression in response to the oxidative environment is a key driver of the altered HSC properties observed in obesity."

Although the effects of chronic organismal stresses are still poorly understood, research is showing that age and environmental stresses can lessen the healthy diversity of cells in our blood-making machinery. "There is now an understanding that the blood stem cell compartment is made up of numerous cell subsets, Keeping this compartment healthy is essential to human health. This includes maintaining the diverse pool of blood-making stem cells needed to produce blood cells the body needs to function properly."