Endocrine Abstracts

NAD+, as well as its phosphorylated form NADP+, are best known as electron carriers and co-substrates of various redox reactions essential to the cellular processes of energy metabolism and biosynthesis. Dynamic changes in NAD+ availability can trigger sensors, such as the protein deacetylase sirtuin enzymes, to adjust cellular and tissue physiology in response to changes in nutrient availability and energy demand. These signalling processes consume NAD+ and release nicotinamide (Nam), necessitating constant replenishment via enzyme mediated recycling of Nam to NAD+. Importantly Vitamin B3, comprising a family of preformed NAD+ precursors, can be salvaged by cells to also augment intracellular NAD+ availability. The combined pathways contributing to dynamic changes in NAD+ homeostasis can also be regulated by multiple systems such as circadian clock, hormones and nutritional status. Given that NAD+ homeostasis is vulnerable to ageing and metabolic disease, we are aiming to delineate the pathways that determine tissue-specific regulation of NAD+ availability. To this end we are identifying how NAD+ metabolism can impact steroid metabolism and muscle energy sensing, and are revealing the role of the nicotinamide riboside kinases in modulating the ability of various Vitamin B3 molecules to augment NAD+ availability, and rewire cellular energy metabolism. Our human clinical studies are investigating how replenishment or augmentation of cellular and tissue NAD+, using Vitamin B3 supplementation, impact systemic and muscle-specific energy metabolism and mitochondrial function. These studies will be help to understand possible ameliorative effects Vitamin B3 may have on ageing or disease phenotypes. Thus, uncovering the range of tissue-specific pathways of NAD+ metabolism could provide key biomarkers and parameters for assessing and modulating organism health.