Dietary supplementation with nicotinamide riboside improves fetal growth under hypoglycemia

Nicotinamide riboside (NR) is considered a super-supplement that prevents obesity and diabetes. While NR has been investigated for various effects depending on nutritional conditions, metabolic research on women and pregnant women has rarely been discussed. In this study, we focused on the glycemic control of NR in females and found the protective role of NR in pregnant animals under hypoglycemic conditions. Metabolic-tolerance tests were performed in vivo under progesterone (P4) exposure after ovariectomy (OVX). NR enhanced resistance to energy deprivation and showed a slight increase in gluconeogenesis in naïve control mice. However, NR reduced hyperglycemia and significantly induced gluconeogenesis in OVX mice. While NR reduced hyperglycemia in the P4-treated OVX mice, it reduced insulin response and substantially increased gluconeogenesis. Similar to animal experiments, NR increased gluconeogenesis and mitochondrial respiration in Hep3B cells. The gluconeogenic function of NR is mediated by tricarboxylic acid cycle (TCA) cycle enrichment, as residual pyruvate could induce gluconeogenesis. NR recovered fetal growth by increasing blood glucose levels when hypoglycemia was induced by diet-restriction during pregnancy. Our study revealed the glucose-metabolic function of NR in hypoglycemic pregnant animals, suggesting NR as a dietary supplement to improve fetal growth. Because diabetic women suffer from hypoglycemia due to insulin therapy, NR has therapeutic potential for use as a glycemic control pill.