Article: NAD+ Restores Heart Function in Heart Failure via Ketone Production: Preclinical Findings

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Metabolic Health Preclinical

NAD+ Restores Heart Function in Heart Failure via Ketone Production: Preclinical Findings

Synopsis

Heart failure with preserved ejection fraction (HFpEF) is a common form of heart failure with few treatment options. This study found that the heart can make ketones using the enzyme HMGCS2, but its activity is reduced when the enzyme is overly acetylated. Replenishing oxidized NAD+ restored HMGCS2 activity, improved fat metabolism, and rescued heart function in HFpEF. However, in mice lacking HMGCS2 specifically in heart cells, NAD+ restoration could not improve heart function. These results show that HMGCS2 is essential for the benefits of NAD+ therapy in HFpEF, linking ketone production, fat metabolism, and mitochondrial health to heart recovery.

Journal

Circulation Research

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