Nicotinamide Phosphoribosyltransferase (Nampt)/Nicotinamide Adenine Dinucleotide (NAD) Axis Suppresses Atrial Fibrillation by Modulating the Calcium Handling Pathway

Int J Mol Sci. 2020 Jun 30;21(13):4655. doi: 10.3390/ijms21134655.


Aging and obesity are the most prominent risk factors for onset of atrial fibrillation (AF). Nicotinamide phosphoribosyltransferase (Nampt) is the rate-limiting enzyme that catalyzes nicotinamide adenine dinucleotide (NAD) activity. Nampt and NAD are essential for maintenance of cellular redox homeostasis and modulation of cellular metabolism, and their expression levels decrease with aging and obesity. However, a role for Nampt in AF is unknown. The present study aims to test whether there is a role of Nampt/NAD axis in the pathogenesis of obesity-induced AF. Male C57BL/6J (WT) mice and heterozygous Nampt knockout (NKO) mice were fed with a normal chow diet (ND) or a high-fat diet (HFD). Electrophysiological study showed that AF inducibility was significantly increased in WT+HFD, NKO+ND, and NKO+HFD mice compared with WT+ND mice. AF duration was significantly longer in WT+HFD and NKO+ND mice and further prolonged in NKO+HFD mice compared with WT+ND mice and the calcium handling pathway was altered on molecular level. Also, treatment with nicotinamide riboside, a NAD precursor, partially restored the HFD-induced AF perpetuation. Overall, this work demonstrates that partially deletion of Nampt facilitated HFD-induced AF through increased diastolic calcium leaks. The Nampt/NAD axis may be a potent therapeutic target for AF.

Keywords: AF; CaMKII; NAD; Nampt; ROS; RyR2; Sirt1; calcium handling; cardiac myocytes.

MeSH terms

  • Animals
  • Atrial Fibrillation / enzymology*
  • Atrial Fibrillation / etiology
  • Calcium / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Diet, High-Fat / adverse effects
  • Heart Atria / enzymology
  • Male
  • Mice, Knockout
  • NAD / metabolism*
  • Nicotinamide Phosphoribosyltransferase / metabolism*
  • Obesity / complications
  • Ryanodine Receptor Calcium Release Channel / metabolism


  • Ryanodine Receptor Calcium Release Channel
  • NAD
  • Nicotinamide Phosphoribosyltransferase
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium