Regulation of muscle satellite cells by adipokines

在过去的十年里，随着全球肥胖症的增加，骨骼肌和脂肪组织之间的相互作用引起了人们的极大兴趣。然而，虽然脂肪细胞分泌的因子（脂肪因子）及其在介导骨骼肌代谢变化中的作用一直备受关注，但这些脂肪因子对肌肉干细胞群的基本生物学的影响几乎是未知的。这些肌肉干细胞，也称为肌肉卫星细胞（MSC），对于维持骨骼肌的代谢和物理能力至关重要，因此，了解脂肪因子-MSC关系的基本生物学具有直接和持久的重要性。在这个提议中，我们将研究选定的脂肪因子对MSC功能的影响。然后，我们将进行生理学研究，以调查是否操纵靶向脂肪因子将影响小鼠骨骼肌的生长和再生能力。我们目前的假设是，脂肪因子的表达模式，与健康动物一致，是维持天然MSC功能所必需的。这种脂肪因子表达模式的改变将促进MSC活化，但对增殖和分化产生负面影响，导致细胞死亡（凋亡）增加。最终，这些损伤将对骨骼肌的生长和再生能力产生负面影响。总之，这些拟议的研究将揭示有关肌肉卫星细胞功能的基础生物学的新信息，并将为未来研究提供基础，以改善脂肪因子谱可能失调的疾病状态下的肌肉健康。

The interplay between skeletal muscle and adipose tissue has garnered much interest in the past decade with the global rise in obesity. However, while much focus has been on adipocyte-secreted factors (adipokines) and their role in mediating metabolic changes to skeletal muscle, the impact these adipokines have on the basic biology of the muscle stem cell population is virtually unknown. These muscle stem cells, also termed muscle satellite cells (MSCs) are vital to maintaining skeletal muscle's metabolic and physical capacities, thus, understanding the basic biology of the adipokine-MSC relationship is of immediate and lasting importance. In this proposal, we will investigate the effects of selected adipokines on MSC function. We will then undertake physiological studies to investigate if manipulation of targeted adipokines will impact the growth and regenerative capacity of mouse skeletal muscle. Our current hypothesis is that adipokine expression patterns, consistent with a healthy animal, are necessary to maintain natural MSC function. Alterations in this adipokine expression pattern will promote MSC activation, but negatively impact proliferation and differentiation, resulting in an increase in cell death (apoptosis). Ultimately, these impairments will negatively impact the growth and regenerative capacities of skeletal muscle. Together, these proposed studies will uncover novel information regarding the basic biology of muscle satellite cell function and will provide a foundation for future research into improving muscle health in disease states where adipokine profiles may be dysregulated.