GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE334nnn/GSE334551/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE334551GEOGSEfalseNAD+ Deficiency Drives Metabolic Dysfunction-Associated Atrial FibrillationAtrial fibrillation (AF) is a cardiometabolic disease with obesity and diabetes as major risk factors. The cellular and molecular mechanisms by which obesity and metabolic stressors drive AF are poorly understood. Here we establish a new mouse model of spontaneous, obesity-induced AF. This two-hit model relies on genetic susceptibility coupled with an environmental factor of diet-induced obesity. Unbiased multi-omics analyses reveal cardiac conduction pathways, inflammation, and metabolic perturbations in AF. We demonstrate atrial NAD+ deficiency as a central pathological mediator in AF. Pharmacological replenishment of atrial NAD+ levels mitigates AF, protects against cardiac remodeling and fibrosis, reduces inflammation, and improves atrial metabolism. These results highlight the role of a metabolic pathway that could be therapeutically targeted for AF.2026/06/24GSE334551GSM9790743GSM9790721GSM9790744GSM9790722GSM9790723GSM9790745GSM9790746GSM9790724GSM9790747GSM9790725GSM9790726GSM9790727GSM9790728GSM9790729GSM9790730GSM9790731GSM9790732GSM9790733GSM9790734GSM9790735GSM9790736GSM9790737GSM9790738GSM9790739GSM9790719GSM9790740GSM9790741GSM9790720GSM97907422424734290334551Mus musculus