Nuclear Myosin 1 links genomic architecture to adipose tissue remodeling, metabolic inflammation and obesity in mice

During adipogenesis, a metabolic shift from oxidative phosphorylation (OXPHOS) to aerobic glycolysis enables preadipocytes to meet the biosynthetic and energetic demands of differentiation. Nuclear myosin 1 (NM1), a chromatin-associated actomyosin motor that regulates transcription and chromatin accessibility, is essential for maintaining OXPHOS. Here, we identify NM1 as a key regulator of adipocyte differentiation and adipose tissue homeostasis. Integration of ATAC-seq and RNA-seq in NM1-deficient mouse embryonic fibroblasts revealed coordinated dysregulation of adipogenic genes ( Insig1, Lipg, Fat1 ) and altered enhancer accessibility near Klf6, Foxo3, Smad5 , and Gata4 . NM1 knockout mesenchymal stem cells showed impaired adipogenic differentiation despite adipocyte hypertrophy. In vivo, NM1-deficient mice developed age-dependent visceral obesity with transcriptional reprogramming in white adipose tissue (WAT), including downregulation of adipogenesis and mitochondrial pathways, and activation of IFNG-, IL33-, and TNF-driven inflammation. Cross-species analysis revealed overlap with MYO1C -centered regulatory modules in human adipose tissue, implicating NM1/ MYO1C in conserved chromatin-based control of adipose biology