De Coppi P, Milan G, Scarda A, Boldrin L, Centobene C, Piccoli M, Pozzobon M, Pilon C, Pagano C, Gamba P, Vettor R
Paediatric Oncohaematology, Stem Cell Transplantation Unit, University of Padua, via Ospedale 105, 35128 Padua, Italy.
Diabetologia. 2006 Aug;49(8):1962-73. doi: 10.1007/s00125-006-0304-6. Epub 2006 Jun 24.
AIMS/HYPOTHESIS: Satellite cells are responsible for postnatal skeletal muscle regeneration. It has been demonstrated that mouse satellite cells behave as multipotent stem cells. We studied the differentiation capacities of human satellite cells and evaluated the effect of the insulin sensitiser rosiglitazone, a well known peroxisome proliferative activated receptor gamma (PPARG) agonist, on their adipogenic conversion.
SUBJECTS, MATERIALS AND METHODS: We obtained human satellite cells from human muscle biopsies of healthy subjects by single-fibre isolation and cultured them under myogenic, osteogenic and adipogenic conditions. Moreover, we compared the morphological features and the adipose-specific gene expression profiling, as assessed by quantitative PCR, between adipocytes differentiated from human satellite cells and those obtained from the stromal vascular fraction of human visceral fat.
We proved by morphological analysis, mRNA expression and immunohistochemistry that human satellite cells are able to differentiate into myotubes, adipocytes and osteocytes. The addition of rosiglitazone to the adipogenic medium strongly activated PPARG expression and enhanced adipogenesis in human satellite cells, but did not in itself trigger the complete adipogenic programme. Moreover, we observed a decrease in wingless-type MMTV integration site family member 10B and an upregulation of growth differentiation factor 8 expression, both being independent of PPARG activation.
CONCLUSIONS/INTERPRETATION: Human satellite cells possess a clear adipogenic potential that could explain the presence of mature adipocytes within skeletal muscle in pathological conditions such as obesity, type 2 diabetes and ageing-related sarcopenia. Rosiglitazone treatment, while enhancing adipogenesis, induces a more favourable pattern of adipocytokine expression in satellite-derived fat cells. This could partially counteract the worsening effect of intermuscular adipose tissue depots on muscle insulin sensitivity.
目的/假设：卫星细胞负责出生后骨骼肌的再生。已证明小鼠卫星细胞具有多能干细胞的特性。我们研究了人类卫星细胞的分化能力，并评估了胰岛素增敏剂罗格列酮（一种著名的过氧化物酶体增殖物激活受体γ（PPARG）激动剂）对其成脂转化的影响。
对象、材料与方法：我们通过单纤维分离从健康受试者的肌肉活检组织中获取人类卫星细胞，并在成肌、成骨和成脂条件下进行培养。此外，我们比较了从人类卫星细胞分化而来的脂肪细胞与从人类内脏脂肪的基质血管部分获得的脂肪细胞在形态特征和通过定量PCR评估的脂肪特异性基因表达谱方面的差异。
我们通过形态分析、mRNA表达和免疫组织化学证明，人类卫星细胞能够分化为肌管、脂肪细胞和骨细胞。在成脂培养基中添加罗格列酮可强烈激活PPARG表达并增强人类卫星细胞的成脂作用，但本身不会触发完整的成脂程序。此外，我们观察到无翅型MMTV整合位点家族成员10B的表达降低以及生长分化因子8的表达上调，两者均与PPARG激活无关。
结论/解读：人类卫星细胞具有明显的成脂潜力，这可以解释在肥胖、2型糖尿病和与衰老相关的肌肉减少症等病理状况下骨骼肌中成熟脂肪细胞的存在。罗格列酮治疗在增强成脂作用的同时，可诱导卫星细胞来源的脂肪细胞产生更有利的脂肪因子表达模式。这可能部分抵消肌肉间脂肪组织库对肌肉胰岛素敏感性的恶化作用。
