Dataset Information


SIRT1-Mediated eNAMPT Secretion from Adipose Tissue Regulates Hypothalamic NAD+ and Function in Mice.

ABSTRACT: 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.


PROVIDER: S-EPMC4426056 | BioStudies | 2015-01-01

REPOSITORIES: biostudies

Similar Datasets

1000-01-01 | S-EPMC4629142 | BioStudies
2007-01-01 | S-EPMC2098698 | BioStudies
2012-01-01 | S-EPMC3469563 | BioStudies
2019-01-01 | S-EPMC6687560 | BioStudies
1000-01-01 | S-EPMC5644507 | BioStudies
2020-01-01 | S-EPMC7559260 | BioStudies
1000-01-01 | S-EPMC5922372 | BioStudies
2013-01-01 | S-EPMC3877362 | BioStudies
1000-01-01 | S-EPMC5579510 | BioStudies
2017-01-01 | S-EPMC6021762 | BioStudies