Regulation of satellite cells by extrinsic factors during recovery from exercise in horses
Brandt, Amanda Maverick
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The vast majority of horses engage in some form of exercise, whether it be for leisure or competition. Despite almost half of the approximately 7.2 million horses engaging in structured athletic work, very little is known about one of the most critical facets of recovery: satellite cells (SCs). Satellite cells lie adjacent to the myofiber of skeletal muscle, poised to enter the myogenic program and fuse to the nearby muscle after a damaging event. Hepatocyte growth factor (HGF) and insulin-like growth factor-1 (IGF-1) transcript abundance increased after an exhaustive bout of endurance exercise in concert with myogenic regulator factors and preceding increased SC abundance in a previous study. This suggests that SCs may participate in repair of exercise-induced muscle damage. To assess the role of HGF in this process, equine SCs (eqSCs) were isolated from the gluteus medius of mature thoroughbred geldings for activation, proliferation and differentiation assays. Activation was not accelerated by 1, 5, 10, or 25 ng/mL HGF. Instead, 25 ng/mL HGF increased the proliferation rate of eqSC via protein kinase C δ and decreased differentiation. The influence of dietary L-citrulline, an amino acid that has the potential to influence SC activity and nutrient availability by its metabolism to L-arginine, was assessed during recovery from exercise in unfit adult horses. To model submaximal exercise, horses were exercised for 1 h at an average heart rate of 116 bpm, suggested to be typical of a heavy exercise session by the National Research Council. L-citrulline decreased myogenin mRNA abundance compared to controls while exercise increased peroxisome proliferator-activated receptor gamma coactivator 1- α (PGC1α) mRNA abundance, a master regulator of energy metabolism, at 1 d post-exercise. Although SCs were not activated in response to a single bout of submaximal exercise, metabolic regulators increased in the early period of recovery. Through these studies eqSC dynamics during exercise are better defined.
General Audience Abstract
The horse is well-known as an athletic creature and is often used in amateur and professional athletic events. Despite its popularity as a pastime in low and high-stakes competition, certain facets directly related to performance during exercise remain relatively unstudied. One crucial component of recovery from exercise is the intrinsic ability of skeletal muscle to repair exercise-induced muscle damage. This is accomplished largely through the incorporation of new nuclei, which originate from a position orbiting the muscle, hence the name satellite cells. This cell is essential to muscle regeneration from injury as often demonstrated in rodent models, but the role of satellite cells in recovery from exercise remains elusive in all species, but particularly so in horses. For instance, whether satellite cells only contribute nuclei after exercise to stimulate gains in muscle mass or whether they may also play a role in the process of adaptation to exercise is not clearly understood. The purpose of my work was to define the response of satellite cells to hepatocyte growth factor, a factor present in skeletal muscle during exercise that is already well-studied in rodent models. Additionally, to determine whether the addition of the non-essential amino acid, citrulline, would influence satellite cells and nutrient reserves after a session of submaximal exercise. I found that hepatocyte growth factor does not influence satellite cells isolated from horses in the same way it influences those from rodents, nor through the same mechanisms. Additionally, I found that satellite cells were not stimulated after a session of submaximal exercise, but a factor involved in regulation of genetic expression that is associated with satellite cells and skeletal muscle was downregulated with the addition of citrulline. Together, these results suggest that satellite cells may behave like other species in some ways, such as some responses to hepatocyte growth factor and the lack of response to a submaximal bout of exercise, but that there is still much to be learned in order to begin to influence management and training decisions as regards skeletal muscle recovery.
- Doctoral Dissertations