Circulating blood eNAMPT drives the circadian rhythms in locomotor activity and energy expenditure.

ABSTRACT: Nicotinamide adenine dinucleotide (NAD⁺) is an essential cofactor of critical enzymes including protein deacetylase sirtuins/SIRTs and its levels in mammalian cells rely on the nicotinamide phosphoribosyltransferase (NAMPT)-mediated salvage pathway. Intracellular NAMPT (iNAMPT) is secreted and found in the blood as extracellular NAMPT (eNAMPT). In the liver, the iNAMPT-NAD⁺ axis oscillates in a circadian manner and regulates the cellular clockwork. Here we show that the hypothalamic NAD⁺ levels show a distinct circadian fluctuation with a nocturnal rise in lean mice. This rhythm is in phase with that of plasma eNAMPT levels but not with that of hypothalamic iNAMPT levels. Chemical and genetic blockade of eNAMPT profoundly inhibit the nighttime elevations in

SUBMITTER: Park JW 

PROVIDER: S-EPMC10082796 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature