(left) Sean J. Morrison, CRI Director and Professor, as well as HHMI Investigator, and Salma Merchant, Ph.D., former Morrison Lab postdoctoral fellow and current research scientist at a biotechnology company.
New research from Children’s Medical Center Research Institute at UT Southwestern (CRI), out today in Cell Stem Cell, shows fatty acid oxidation — the process that breaks down fatty acids to produce energy — occurs in hematopoietic, or blood-forming, stem cells (HSCs) and can promote or inhibit HSCs function, depending age and diet.
Former Morrison Lab postdoctoral fellow Salma Merchant, Ph.D., now a research scientist at a biotechnology company, along with Sean J. Morrison, CRI Director and Professor, as well as HHMI Investigator, and colleagues used 14C-palmitate tracing and metabolomic analysis of hematopoietic stem/progenitor cells (HSPCs) to show that long-chain fatty acid oxidation depends upon CPT1a and HADHA enzymes.
CPT1a or HADHA deficiency had little or no effect on HSPCs or hematopoiesis in young adult mice. Young HSPCs had the plasticity to oxidize other substrates, including glutamine, and appeared to compensate for the loss of fatty acid oxidation by increasing the function of pyruvate dehydrogenase.
This metabolic plasticity declined as mice aged, when CPT1a or HADHA deficiency altered blood cell production and impaired HSC function.
In addition, a high-fat diet increased fatty acid oxidation and reduced HSC function. HSC function was rescued by CPT1a or HADHA deficiency, demonstrating increased fatty acid oxidation can undermine HSC function.
Drs. Merchant and Morrison have discovered, therefore, that long-chain fatty acid oxidation is dispensable in young HSCs but necessary during aging and harmful with a high fat diet.
About CRI
Children’s Medical Center Research Institute at UT Southwestern (CRI) is a joint venture of UT Southwestern Medical Center and Children’s Medical Center Dallas. CRI’s mission is to perform transformative biomedical research to better understand the biological basis of disease. Located in Dallas, Texas, CRI is home to interdisciplinary groups of scientists and physicians pursuing research at the interface of regenerative medicine, cancer biology and metabolism.
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