| First Author | Yoon MJ | Year | 2015 |
| Journal | Cell Metab | Volume | 21 |
| Issue | 5 | Pages | 706-17 |
| PubMed ID | 25921090 | Mgi Jnum | J:269580 |
| Mgi Id | MGI:6273590 | Doi | 10.1016/j.cmet.2015.04.002 |
| Citation | Yoon MJ, et al. (2015) SIRT1-Mediated eNAMPT Secretion from Adipose Tissue Regulates Hypothalamic NAD+ and Function in Mice. Cell Metab 21(5):706-17 |
| abstractText | Nicotinamide phosphoribosyltransferase (NAMPT), the key NAD(+) biosynthetic enzyme, has two different forms, intra- and extracellular (iNAMPT and eNAMPT), in mammals. However, the significance of eNAMPT secretion remains unclear. Here we demonstrate that deacetylation of iNAMPT by the mammalian NAD(+)-dependent deacetylase SIRT1 predisposes the protein to secretion in adipocytes. NAMPT mutants reveal that SIRT1 deacetylates lysine 53 (K53) and enhances eNAMPT activity and secretion. Adipose tissue-specific Nampt knockout and knockin (ANKO and ANKI) mice show reciprocal changes in circulating eNAMPT, affecting hypothalamic NAD(+)/SIRT1 signaling and physical activity accordingly. The defect in physical activity observed in ANKO mice is ameliorated by nicotinamide mononucleotide (NMN). Furthermore, administration of a NAMPT-neutralizing antibody decreases hypothalamic NAD(+) production, and treating ex vivo hypothalamic explants with purified eNAMPT enhances NAD(+), SIRT1 activity, and neural activation. Thus, our findings indicate a critical role of adipose tissue as a modulator for the regulation of NAD(+) biosynthesis at a systemic level. |
