Credit: Georges Seguin
Acetate, the major component of vinegar, can stimulate erythropoiesis in anemic mice, according to research published in Nature Medicine.
The study suggests acetate supplements could eventually be a suitable addition or even an alternative to erythropoietin (EPO) therapy.
“[W]e may be able to treat acutely or chronically anemic patients with acetate supplements and thereby reduce the need for blood transfusions or erythropoietin therapy,” said Joseph Garcia, MD, PhD, of the UT Southwestern Medical Center in Dallas, Texas.
He and his colleagues began this study by identifying a pathway that controls erythropoiesis in conditions of stress, such as hypoxia.
Studying genetically modified mice, the researchers discovered that hypoxia stimulates the production of acetate. Acetate, in turn, activates a molecular pathway that ultimately results in erythropoiesis by triggering EPO production.
EPO is regulated by the stress-responsive transcription factor hypoxia-inducible factor-2 (HIF-2). And the researchers had previously shown that the lysine acetyltransferase CREB-binding protein (CBP) is required for HIF-2a acetylation and efficient HIF-2-dependent EPO induction during hypoxia.
With this study, the team found that these processes require acetate-dependent acetyl CoA synthetase 2 (ACSS2) as well.
Experiments showed that ACSS2 is required for HIF-2a acetylation, CBP-HIF-2a complex formation, CBP-HIF-2a recruitment to the EPO enhancer, and efficient induction of EPO gene expression.
The researchers administered acetate to acutely anemic mice and found the treatment augments stress erythropoiesis in an ACSS2-dependent manner.
When they administered acetate to mice with acquired and inherited chronic anemia, the team observed increases in EPO expression and resting hematocrit.
“Our study shows that acetate functions as a biochemical ‘flare,’” Dr Garcia said, “linking changes in cell metabolism that occur during hypoxia with the activation of a selective stress signaling pathway.”
