Maternal Nicotinamide Riboside Enhances Postpartum Weight Loss, Juvenile Offspring Development, and Neurogenesis of Adult Offspring

Conditions of metabolic stress dysregulate the NAD metabolome. By restoring NAD, nicotinamide riboside (NR) provides resistance to such conditions. We tested the hypotheses that postpartum might dysregulate maternal NAD and that increasing systemic NAD with NR might benefit mothers and offspring. In...

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Published in:	Cell reports (Cambridge) Vol. 26; no. 4; pp. 969 - 983.e4
Main Authors:	Ear, Po Hien, Chadda, Ankita, Gumusoglu, Serena B., Schmidt, Mark S., Vogeler, Sophia, Malicoat, Johnny, Kadel, Jacob, Moore, Michelle M., Migaud, Marie E., Stevens, Hanna E., Brenner, Charles
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 22-01-2019
Subjects:	adult hippocampal neurogenesis Animals BDNF caudate-putamen Female homeorhesis lactation Lactation - drug effects Lactation - metabolism Liver - metabolism Liver - pathology Maternal Exposure - adverse effects metabolic stress Mice NAD NAD - metabolism Neurogenesis - drug effects Niacinamide - adverse effects Niacinamide - analogs & derivatives Niacinamide - pharmacology nicotinamide riboside postpartum Postpartum Period - metabolism Pregnancy Prenatal Exposure Delayed Effects - chemically induced Prenatal Exposure Delayed Effects - metabolism Prenatal Exposure Delayed Effects - pathology prolactin Weight Loss - drug effects NAD homeorhesis prolactin caudate-putamen adult hippocampal neurogenesis BDNF lactation postpartum metabolic stress nicotinamide riboside
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Summary:	Conditions of metabolic stress dysregulate the NAD metabolome. By restoring NAD, nicotinamide riboside (NR) provides resistance to such conditions. We tested the hypotheses that postpartum might dysregulate maternal NAD and that increasing systemic NAD with NR might benefit mothers and offspring. In postpartum mothers, the liver NAD metabolome is depressed while blood increases circulation of NAD metabolites to enable a >20-fold increase in mammary NAD+ and NADP+. Lactation and NR synergize in stimulating prolactin synthesis and mammary biosynthetic programs. NR supplementation of new mothers increases lactation and nursing behaviors and stimulates maternal transmission of macronutrients, micronutrients, and BDNF into milk. Pups of NR-supplemented mothers are advantaged in glycemic control, size at weaning, and synaptic pruning. Adult offspring of mothers supplemented during nursing retain advantages in physical performance, anti-anxiety, spatial memory, delayed onset of behavioral immobility, and promotion of adult hippocampal neurogenesis. Thus, postgestational maternal micronutrition confers lasting advantages to offspring. [Display omitted] •Postpartum liver circulates NAD metabolites to increase mammary NAD+ and NADP+ >20-fold•NR supplementation superinduces prolactin, mammary biosynthetic programs, and lactation•Weanlings of NR-fed mothers are hypoglycemia resistant and advanced in motor learning•Adult offspring of NR-fed mothers retain striking physical and behavioral advantages Postpartum constitutes a profound episode of metabolic stress. Ear et al. show that nicotinamide riboside supplementation of rodent mothers relieves postpartum metabolic stress and increases lactation, nursing behavior, and transmission of brain-derived neurotrophic factor into milk, resulting in improved physical and neurobehavioral development of offspring, whose advantages persist into adulthood.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2211-1247 2211-1247
DOI:	10.1016/j.celrep.2019.01.007