Regulation of muscle satellite cells by adipokines

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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.