The feedback mechanism between the hypothalamus and adipose tissue that maintains hypothalamic NAD+ levels through the secretion of eNAMPT.36 In adipose tissue, iNAMPT is acetylated, and SIRT1 specifically deacetylates lysine 53 and predisposes iNAMPT to secretion in a NAD+-dependent manner. eNAMPT secreted from adipose tissue remotely promotes NAD+ biosynthesis in the hypothalamus likely through the extracellular synthesis of NMN and enhances SIRT1 activity and neural activity. In the DMH, SIRT1 and its binding partner NKX2-1 regulate the transcription of Prdm13 (PR domain-containing protein 13), which controls the quality of sleep and adiposity. This NAD+/SIRT1-mediated eNAMPT-secreting function of adipose tissue positions this tissue to be a modulator/sensor in the system. Adipose tissue might also have another NAD+-sensing mechanism that could affect the functions of other organs and tissues. DMH, dorsomedial hypothalamic nuclei.