Key result
Nicotinamide riboside and pterostilbene improve postpartum survival and cardiac metabolites in mitochondrial cardiomyopathy mice.
Why the study?
Peripartum/postpartum cardiomyopathy increases the risk of major cardiac events following pregnancy, but its underlying molecular mechanisms remain poorly understood.
Does dietary supplementation with nicotinamide riboside and pterostilbene improve postpartum survival and preserve cardiac energy metabolites in a mouse model of CHCHD10 mitochondrial cardiomyopathy?
Does dietary supplementation with nicotinamide riboside and pterostilbene improve postpartum survival and preserve cardiac energy metabolites in a mouse model of CHCHD10 mitochondrial cardiomyopathy?
In a mouse model of CHCHD10 mitochondrial cardiomyopathy, the high energy demands of pregnancy and labor precipitate fatal metabolic failure, which can be mitigated by dietary NAD(H) supplementation.
Extends NAD+ precursor evidence to a postpartum mitochondrial cardiomyopathy model; hypothesis-generating and should not change clinical practice.
During pregnancy, the heart undergoes major physiological and metabolic changes to increase cardiac workload and the demand for energy production is especially elevated during the trial of labor. Normally, cardiac structure and metabolism revert to the pre-pregnancy state shortly after delivery. However, in some cases peripartum/postpartum cardiomyopathy (PPCM) occurs, which increases a person’s risk of major cardiac events following pregnancy. The molecular mechanisms underlying PPCM remain poorly understood. In this study, we investigate the transcriptional, metabolic, and bioenergetic profiles of postpartum (PP) hearts in a mouse model of cardiomyopathy caused by the pathogenic p.S55L mutation in the mitochondrial protein coiled-coil-helix-coiled-coil-helix domain containing 10 (CHCHD10). Heterozygote p.S55L mutant CHCHD10 mice develop acute heart failure during the immediate PP period. We observe cardiac remodeling, mitochondrial stress, and profound metabolic rewiring in PP mutant CHCHD10 hearts. Metabolic rewiring results decreased levels of heme and the depletion of key cofactors of energy metabolism, including NAD(H) and ADP. These findings suggest that mutant CHCHD10 hearts fail to meet the increased energy demands associated with the trial of labor due to the insufficient turnover rate of NAD+/NADH and ADP/ATP. We propose that this metabolic insufficiency drives PP mortality in mutant CHCHD10 mice. In support of this hypothesis, dietary supplementation with nicotinamide riboside and pterostilbene, a naturally derived polyphenol, increased PP survival and cardiac energy metabolites in mutant CHCHD10 mice. Our work provides novel insights into the molecular mechanisms of PP cardiomyopathy associated with mitochondrial stress and suggests potential beneficiary effects of dietary NAD(H) supplementation. • p.S55L CHCHD10 mutation causes postpartum mortality in female mice • Mitochondrial integrated stress response favors antioxidant over energy metabolites • Pregnancy induces a depletion of key energy metabolites in D10 S55L hearts • High energy demands during labor precipitate metabolic failure in D10 S55L hearts • Nicotinamide riboside and pterostilbene improve PP survival in D10 S55L mice
No takes yet. Share an insight, caveat, or question.
Sayles et al. (2026) studied Peripartum/postpartum cardiomyopathy (PPCM) in a mitochondrial cardiomyopathy model. Nicotinamide riboside and pterostilbene vs. Unsupplemented diet was evaluated on Postpartum survival and cardiac energy metabolites. Dietary supplementation with nicotinamide riboside and pterostilbene increased postpartum survival and cardiac energy metabolites in a mouse model of mitochondrial cardiomyopathy.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: