The glucose-to-acetate metabolic flux that drives endothelial-to-mesenchymal transition via TGF-β signaling

The metabolic mechanisms supporting the process of endothelial-to-mesenchymal transition (EndMT) remain largely unknown. Here, Zhu et al. describe a novel role for acetate and ACC2 in regulating EndMT and atherosclerosis via modulation of the TGF-β signaling. This study sheds light on the role of glucose-derived metabolites that drive endothelial pathophysiology. The metabolic mechanisms supporting the process of endothelial-to-mesenchymal transition (EndMT) remain largely unknown. Here, Zhu et al. describe a novel role for acetate and ACC2 in regulating EndMT and atherosclerosis via modulation of the TGF-β signaling. This study sheds light on the role of glucose-derived metabolites that drive endothelial pathophysiology. Acetate controls endothelial-to-mesenchymal transitionZhu et al.Cell MetabolismJune 15, 2023In BriefEndothelial-to-mesenchymal transition (EndMT) is initiated by activation of endothelial TGF-β signaling. Induction of EndMT results in increased ACSS2-dependent Ac-CoA synthesis from pyruvate-derived acetate. Increased Ac-CoA production leads to acetylation of the TGF-β receptor ALK5 and SMADs 2 and 4, resulting in the activation and long-term stabilization of TGF-β signaling. Full-Text PDF