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

## TL;DR

Nuclear Myosin 1 is essential for proper fat cell development and metabolic health in mice, and its absence leads to obesity and inflammation.

## Contribution

This study identifies NM1 as a chromatin-level regulator linking genomic architecture to adipose tissue remodeling and metabolic inflammation.

## Key findings

- NM1 deficiency disrupts adipocyte differentiation and lipid droplet formation in mouse cells.
- NM1 KO mice develop visceral obesity and show metabolic and inflammatory changes in white adipose tissue.
- MYO1C is highlighted as a conserved regulator of adipose tissue remodeling across species.

## Abstract

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.