Different effects of fatty acid oxidation on hematopoietic stem cells based on age and diet
Year: 2024
Type: article
Abstract: C-palmitate tracing and metabolomic analysis that hematopoietic stem/progenitor cells (HSPCs) engage in long-chain fatty acid oxidation that depends upon carnitine palmitoyltransferase 1a (CPT1a) and hydroxyacyl-CoA dehydrogenase (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 compensated for loss of fatty acid oxidation by decreasing pyruvate dehydrogenase phosphorylation, which should increase function. This metabolic plasticity declined as mice aged, when CPT1a or HADHA deficiency altered hematopoiesis and impaired hematopoietic stem cell (HSC) function upon serial transplantation. A high-fat diet increased fatty acid oxidation and reduced HSC function. This was rescued by CPT1a or HADHA deficiency, demonstrating that increased fatty acid oxidation can undermine HSC function. Long-chain fatty acid oxidation is thus dispensable in young HSCs but necessary during aging and deleterious with a high-fat diet.
Source: Cell stem cell
Authors: Salma Merchant, Animesh Paul, Amanda Reyes, Daniel Cassidy, Ashley Leach, Dohun Kim, Sarah Muh, Gerik Grabowski, Gerta Hoxhaj, Zhiyu Zhao, Sean J. Morrison
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $9,350
Funders: Foundation for the National Institutes of Health, Howard Hughes Medical Institute, Cancer Prevention and Research Institute of Texas, University of Texas Southwestern Medical Center, National Institutes of Health, National Institute on Aging, National Institute of Diabetes and Digestive and Kidney Diseases
OpenAlex ID: W4405638489