Altered behavioral and metabolic circadian rhythms in mice with disrupted NAD+ oscillation

Saurabh Sahar, Veronica Nin, Maria Thereza Barbosa, Eduardo Nunes Chini, Paolo Sassone-Corsi

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

The Intracellular levels of nicotinamide adenine dinucleotide (NAD+) are rhythmic and controlled by the circadian clock. However, whether NAD+ oscillation in turn contributes to circadian physiology is not fully understood. To address this question we analyzed mice mutated for the NAD+ hydrolase CD38. We found that rhythmicity of NAD+ was altered in the CD38-deficient mice. The high, chronic levels of NAD+ results in several anomalies in circadian behavior and metabolism. CD38-null mice display a shortened period length of locomotor activity and alteration in the rest-activity rhythm. Several clock genes and, interestingly, genes involved in amino acid metabolism were deregulated in CD38-null livers. Metabolomic analysis identified alterations in the circadian levels of several amino acids, specifically tryptophan levels were reduced in the CD38-null mice at a circadian time paralleling with elevated NAD+ levels. Thus, CD38 contributes to behavioral and metabolic circadian rhythms and altered NAD+ levels influence the circadian clock.

Original languageEnglish (US)
Pages (from-to)794-802
Number of pages9
JournalAging
Volume3
Issue number8
DOIs
StatePublished - Aug 2011

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Keywords

  • Amino acid metabolism
  • CD38
  • Circadian rhythm
  • Clock

ASJC Scopus subject areas

  • Aging
  • Cell Biology

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