Recipient Organization
VIRGINIA POLYTECHNIC INSTITUTE
(N/A)
BLACKSBURG,VA 24061
Performing Department
(N/A)
Non Technical Summary
The horse industry is a vital cog in the US economy generating nearly $120-billion annually. The athletic prowess of the horse demands large energy expenditures during muscle movement which often leads to damage. Repair of skeletal muscle, and tissue growth, necessitates the activities of muscle stem cells (satellite cells, SCs). These cells, however, are a mix of multiple subtypes with each likely playing distinct roles. To facilitate muscle growth and repair, an improved understanding of how these cells differ from one another, how their actions are initiated following metabolic challenges and how nutrition can regulate the timing of their activation is required. Using molecular and biochemical tools, we expect to find rapid-fusing SC that lay the foundation for early repair and growth and a second population responsible for generating SC precursors. Supplementing butyrate-products to horses will alter the fiber metabolism and initiate SC activity. Completion of the proposed experiments will assist with muscle recovery from exercise thus, improving the health and welfare of the horse. Equally important, filling the knowledge voids surrounding SC bioactivities can translate directly to livestock production leading to an improved efficiency of lean muscle deposition and contributing to a sustainable food supply.
Animal Health Component
20%
Research Effort Categories
Basic
80%
Applied
20%
Developmental
(N/A)
Goals / Objectives
The requirement for satellite cells (SCs) for muscle growth is unequivocal thus, supporting the need for an improved understanding of their regulatory control in the postnatal animal. While a vast amount of literature details the importance of the fiber niche to SC function, a gap in knowledge exists in how modification of said niche can alter bioactivity of the heterogeneous population.The grant hypothesis is that multiple subsets of SC exist whose bioactivities can be augmented through dietary modification of the systemic milieu, muscle fiber metabolome and its lamin associated niche. Specifically the goals of the project are to 1) identify distinct fusogenic and self-renewing SCs subclasses and 2) examine the functional outcomes of oxidative and glycolytic fiber metabolism on the adjacent SC and its supporting niche.
Project Methods
The experiments will define the heterogeneity within the SC population using molecular and cellular methods. Specifically, SC will be isolated from muscle biopsies as a function of time post-exercise and individual transcriptomes sequenced. Bioinformatics will be used to establish the numbers of subclasses and the genetic signatures unique to each. A second set of SCs will be cultured in vitro with chemical agonists and antagonists to identify growth factor-mediated signaling pathways that control self-renewal and fusion. Butyrate-based nutraceuticals will be fed to horses and muscle biopsies obtained pre and post-exercise for the measurement of fiber metabolism (glycolysis, fatty acid oxidation), niche composition of growth factors and cytokines and activities of the newly identified subclasses of SCs. Experimental results in all instances are analyzed using conventional statistical software. The efforts will be evaluated through the peer-review process for publication in established journals (2/yr), abstract submissions to professional society meetings (2/yr), and presentations at scientific meetings by students and PD (2/yr). The change in knowledge from these efforts will be quantified by numbers of paper citations, numbers of student interns involved in the research, numbers of graduate students participating in the work and graduating, and numbers of stakeholder attendees at public forums.