Abstract Body: Pregnancy induces profound cardiac remodeling. It is often assumed that postpartum reversion follows a uniform trajectory toward the baseline state. However, lactation represents a point of diversion: not all women breastfed, and breastfeeding duration varies. Lactation represents a major systemic metabolic perturbation during the postpartum period. Interestingly, although lactation is associated with reduced long-term cardiovascular risk, its direct impact on maternal postpartum cardiac remodeling has not been defined. I hypothesized that lactation drives unique postpartum cardiac remodeling trajectories and sought to define the systemic and cardiac mechanisms underlying this pivot.
I compared lactating (L), non-lactating postpartum (NL), and age-matched non-pregnant (NP) C57BL/6J mice. L mice nursed for 7 days postpartum; NL controls were separated within 24 hours of delivery to suppress lactation and assessed at day 7. Whole-body metabolism was assessed by indirect calorimetry, and organ phenotyping was performed. Cardiac remodeling was interrogated using bulk RNA-seq, proteomics, and metabolomics.
NL mice rapidly converged toward an NP-like metabolic phenotype following pup separation, whereas L mice exhibited marked systemic reprogramming, including persistently elevated RER (>1). Lactation drove robust organ remodeling, with increased body (28.8%), heart (26%), and liver weight (76.3%) by postpartum day 7. Liver mass normalized by three weeks post-weaning, while cardiac hypertrophy persisted. Multi-omics revealed layered divergence between trajectories: transcriptomic profiles strongly separated L from NL and NP, proteomics indicated NL hearts were most distinct from NP consistent with an active reverse-remodeling phase, and metabolomics showed the greatest divergence in L consistent with sustained energetic demand.
Lactation status defines divergent postpartum cardiac remodeling trajectories, separating rapid reverse remodeling after weaning from sustained remodeling under continued metabolic load. These findings identify lactation as a key determinant of postpartum cardiac biology and provide a framework for dissecting the mechanisms governing adaptive versus persistent maternal cardiac remodeling. Given that lactation duration correlates with reduced long-term cardiovascular risk, defining the metabolic and cellular mechanisms by which lactation alters postpartum cardiovascular remodeling may offer insight into its cardioprotective effects.