Obesity triggers skeletal muscle physio-pathological alterations. However, the crosstalk between adipose tissue and myogenic cells remains poorly understood during obesity. We identified NID-1 among the adipose tissue secreted factors impairing myogenic potential of human myoblasts and murine muscle stem cells in vitro. Mice under High Fat Diet (HFD) displayed increased NID-1 expression in the skeletal muscle endomysium associated with intramuscular fat adipose tissue expansion and compromised muscle stem cell function. We show that NID-1 is highly secreted by skeletal muscle fibro-adipogenic/mesenchymal progenitors (FAPs) during obesity. We demonstrate that increased muscle NID-1 impairs muscle stem cells proliferation and primes the fibrogenic differentiation of FAPs, giving rise to an excessive deposition of extracellular matrix. Finally, we propose a model in which obesity leads to skeletal muscle extracellular matrix remodeling by FAPs, mediating the alteration of myogenic function by adipose tissue and highlighting the key role of NID-1 in the crosstalk between adipose tissue and skeletal muscle.

肥胖会引发骨骼肌生理病理改变。然而，脂肪组织和生肌细胞之间的串扰在肥胖期间仍然知之甚少。我们在体外损害人成肌细胞和小鼠肌肉干细胞的肌原性潜能的脂肪组织分泌因子中鉴定出 NID-1. 高脂肪饮食 (HFD) 下的小鼠在骨骼肌肌内膜中表现出增加的 NID-1 表达，这与肌内脂肪脂肪组织扩张和受损的肌肉干细胞功能有关。我们表明 NID-1 在肥胖期间由骨骼肌纤维脂肪生成/间充质祖细胞 (FAP) 高度分泌。我们证明增加的肌肉 NID-1 会损害肌肉干细胞增殖并引发 FAP 的纤维化分化，从而导致细胞外基质的过度沉积。最后，我们提出了一个模型，其中肥胖通过 FAP 导致骨骼肌细胞外基质重塑，通过脂肪组织调节生肌功能的改变，并强调 NID-1 在脂肪组织和骨骼肌之间的串扰中的关键作用。