LAUSR

Objectives We tested the hypothesis that postpartum constitutes a metabolic stress to the nicotinamide adenine dinucleotide (NAD) system and that supplementation of mothers during postpartum with nicotinamide riboside (NR) might improve health outcomes to mothers and offspring. Methods Males impregnated female C57BL6 mice and Fisher 344 rats, who were fed a normal chow (NC) diet until they produced litters. At parturition, females were sorted into cages with pups, where they were either fed NC or NC supplemented with 3 grams of NR/kg of the diet. Lactation was measured at days 7, 14 & 21. Maternal weight change was measured from the day of parturition to the day of weaning. At weaning, offspring were moved to cages with NC. Some mothers and pups were sacrificed at day 14. Pups were analyzed at various times into adulthood for physiological, physical, neurodevelopmental and neurobehavioral phenotypes. Results We discovered that postpartum rewires the maternal NAD system such that the liver NAD metabolome is depressed to circulate higher levels of NAD metabolites in blood. The mammary in a lactating dam is increased by > 20-fold in levels of NAD and NADP. When postpartum female rodents are supplemented with NR, they maintain their liver NAD metabolome and superinduce blood and mammary NAD while also circulating more prolactin. This superinduces mammary biosynthetic programs. NR-supplemented mothers produce more milk, are advantaged in post-gestational weight loss and produce larger weanlings than NC-fed mothers. Offspring of NR-supplemented mothers have striking advantages in glycemic control, motor activity and motor learning as juveniles. Adult offspring of NR-supplemented mothers retained greater physical capabilities, were less anxious, had less depressive-like behavior and greater spatial memory than offspring of NC-fed mothers. NR-supplemented mothers produce more BDNF in their milk and offspring of NR-supplemented mothers have an advantage in adult hippocampal neurogenesis. Conclusions The data show that NAD limits multiple maternal functions including lactation and expression of BDNF into milk and that improved maternal micronutrition has lasting neurodevelopmental, physical and neurobehavioral benefits to offspring. Funding Sources ChromaDex & Roy J Carver Trust. Supporting Tables Images and/or Graphs