Univ Paris Est Creteil, INSERM, IMRB, F-94010 Creteil, France.
Sorbonne Université, INSERM, UMRS974, Center for Research in Myology, F-75013, Paris, France.
Matrix Biol. 2022 Sep;112:90-115. doi: 10.1016/j.matbio.2022.08.006. Epub 2022 Aug 11.
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.
肥胖会引发骨骼肌的生理病理改变。然而，在肥胖过程中，脂肪组织和肌源性细胞之间的串扰仍知之甚少。我们在体外鉴定出了一种脂肪组织分泌因子 NID-1，它会损害人类成肌细胞和鼠肌肉干细胞的成肌潜能。高脂饮食（HFD）喂养的小鼠，其骨骼肌内膜中的 NID-1 表达增加，与肌内脂肪组织扩张和肌肉干细胞功能受损有关。我们发现，肥胖期间骨骼肌成纤维脂肪形成/间充质祖细胞（FAP）会大量分泌 NID-1。我们证明，肌肉中 NID-1 的增加会抑制肌肉干细胞的增殖，并促使 FAP 向成纤维细胞分化，导致细胞外基质的过度沉积。最后，我们提出了一个模型，即肥胖通过 FAP 导致骨骼肌细胞外基质重塑，介导脂肪组织对成肌功能的改变，并强调了 NID-1 在脂肪组织和骨骼肌串扰中的关键作用。
