Unravelling the Impact of Adipokines on Muscle Satellite Cell Regulation

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The role of adipocyte-secreted signaling molecules (adipokines) in altering skeletal muscle metabolism has garnered much interest in the past twenty years with the global rise in obesity. However, the impact of adipokines on muscle's Satellite Cell (MSC) population, the stem cells of muscle, is virtually unknown. Consistent with our long-term objective to uncover novel regulators of MSCs, we propose to investigate the effects of selected adipokines on MSC function and determine if manipulating adipokine levels will impact the ability of mouse skeletal muscle to grow or repair from injury. We hypothesize that altering these adipokine levels will negatively impact MSC function and ultimately attenuate skeletal muscle growth and regeneration.******To address this hypothesis, our 5 year plan will seek to achieve the following goals: ***Goal #1: Define the impact of specific adipokines on MSC function***In vitro studies will be used to investigate the effects of manipulating selected adipokine levels (alone and in combination) on primary MSCs. Initial experiments will test: Lipocalin-2, Retinol binding protein-4, Vaspin and Resistin. Primary MSC cultures and isolated single muscle fibres will be used to assess the capacity for MSC activation, proliferation and differentiation in response to varying adipokine expression. We will also assess the ability of selected adipokines to induce epigenetic changes on MSC. ***Goal #2: Understand the effects of altered adipokine levels on skeletal muscle growth es and I have the demonstrated infrastructure/expertise in the proposed techniques and the support network (colleagues, collaborators) to ensure the successful completion of the proposed studies.******The research proposed herein will uncover novel insight into the basic biology of MSC function as well as provide a foundation for future pharmaceutical and medical research into improving muscle quality in conditions where adipokine levels may be dysregulated (obesity, lipodystrophy). Given the known relationship between skeletal muscle health and longevity, these foundational studies are of immediate and lasting importance. This research will also provide the platform for the training of >10 graduate and undergraduate students in the areas of physiology, cellular/molecular biology and biochemistry; high-demand areas within industry, academia, patent law and education.