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

Adipocyte differentiation involves a metabolic transition from oxidative phosphorylation (OXPHOS) to aerobic glycolysis, allowing preadipocytes to meet the biosynthetic and energetic demands of maturation. Here, we show that nuclear myosin 1 (NM1), a chromatin-associated actomyosin motor, known to control transcription and chromatin accessibility, is required for metabolic homeostasis during adipocyte differentiation. Integrated ATAC-seq and RNA-seq profiling of NM1-deficient mouse embryonic fibroblasts (MEFs) revealed coordinated downregulation of key adipogenic and lipid-droplet machinery genes like Cebpa, Plin2, Abhd5, Agpat2, Pink1, and altered enhancer accessibility near adipogenesis-linked transcription factors (TFs) such as Klf6, Foxo3, Smad5, and Gata4. NM1 knockout (KO) mesenchymal stem cells (MSCs) exhibited impaired differentiation potential despite enlarged adipocyte morphology. In vivo, NM1-deficient mice developed progressive visceral obesity, accompanied by transcriptional reprogramming in epididymal white adipose tissue (eWAT), including repression of mitochondrial and adipogenic pathways and activation of inflammatory networks driven by IFNG, IL33, and TNF. Cross-species network analysis highlighted conserved regulatory architecture centered on MYO1C, implicating NM1/MYO1C as key chromatin-level regulators of adipose remodeling.