Maternal adaptations in mouse lactation are vulnerable to diet-induced excess adiposity

Abstract Lifetime maternal risk of obesity is increased by excess gestational weight gain, which alters maternal metabolic adaptations in pregnancy, but the effects of excess weight retention/adiposity in the early postpartum period have not been extensively studied. The pathophysiology of excess adiposity and its accompanying immunometabolic dysregulation are associated with impaired intestinal barrier function in both non-pregnant and pregnant contexts. Using a mouse model, we investigated effects of diet-induced excess adiposity on maternal physiological adaptations during lactation. We report that in lactation, excess adiposity altered maternal intestinal morphology, influenced local immune cell composition and phenotype, increased intestinal permeability, and altered whole-body glucose metabolism as well as peripheral inflammation and immune cell composition. Many of these effects persisted two months post-lactation in mice with excess adiposity. Our findings have important implications for the development of interventions for periconceptual/perinatal excess adiposity and emphasize that further studies are needed to better understand effects of excess adiposity on maternal postpartum health.