NAD+ oscillation and hypothalamic neuronal functions

Abstract

A substantial body of evidence shows the importance of nicotinamide adenine dinucleotide (NAD(+)) biosynthesis and its regulation in a wide range of cellular metabolism. The expression of nicotinamide phosphoribosyltransferase (NAMPT) is regulated in a circadian manner by the core clock mechanism and NAD(+)-dependent sirtuins, producing the circadian oscillation of NAD(+). The hypothalamus is a critical center for the homeostatic regulation of metabolism, circadian rhythm, and age-associated physiology. The dysfunction of systemic NAD(+) biosynthesis over age affects the functions of hypothalamic neurons, causing age-associated metabolic pathophysiologies, including obesity and age-associated diseases. These recent studies suggest that NAD(+) oscillation contributes to the hypothalamic function, and its disruption produces circadian and aging-related metabolic disorders. Furthermore, new studies have demonstrated a novel intertissue NAD(+)-dependent communication as a potential target for preventing and treating such disorders and for extending the health span of humans.