27 Sep 2023
Inhibition of fatty acid oxidation enables heart regeneration in adult mice
https://www.nature.com/articles/s41586-023-06585-5
Put simply: after birth, cardiomyocytes undergo maturation, shifting from glycolysis to fatty acid oxidation, which limits heart regeneration. By disabling fatty acid oxidation, the researchers observed increased resistance to hypoxia and stimulated cardiomyocyte (cardiac muscle) proliferation following heart injury. Metabolic changes, including elevated alpha-ketoglutarate (αKG) levels, activated KDM5, which demethylated genes involved in cardiomyocyte maturation, promoting proliferation and suggesting a pathway for heart repair through metabolic and epigenetic regulation.
According to another article [0], FTO has been shown to inhibit the expression of PPARα which is a key regulator of fatty acid oxidation. So logically, inhibit FTO ==> promote PPARα ==> decrease fatty acid oxidation ==> regenerate heart cells?
I think this adds weight to @Davisite's hypothesis that bisantrene not only protects but also regenerates heart muscle [1] and also supports @Boffin99's hypothesis re. ferroptosis. Any thoughts?
[0] https://lipidworld.biomedcentral.com/articles/10.1186/s12944-022-01640-y
[1] See RAC announcement 08 Dec 2021 "Expanded heart protection discovery for Zantrene"
27 Sep 2023Inhibition of fatty acid oxidation enables heart...
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