Importance of fatty acid oxidation in hematopoietic stem cells based on age and diet
The importance of fatty acid oxidation (FAO) in most stem cells is not clearly not understood.
The researchers show long-chain fatty acid oxidation has context dependent effects on hematopoietic stem cells (HSCs).
It is dispensable for HSC function in young mice. It becomes necessary for normal HSC function and hematopoiesis in older mice and depends upon carnitine palmitoyltransferase 1a (CPT1a) and hydroxyacyl-CoA dehydrogenase (HADHA) enzymes.
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 increases fatty acid oxidation, and this impairs HSC function. This was rescued by CPT1a or HADHA deficiency, demonstrating that increased fatty acid oxidation can undermine HSC function.
https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(24)00413-2
