Skeletal muscle growth retardation occurs due to a variety of conditions. Malnutrition, trauma, and inactivity restrict growth and often lead to muscle atrophy. At the present time, little is known about the molecular regulation of muscle growth recovery; and there are no studies defining optimal treatments for long-term recovery. Our preliminary studies suggest that the factor that limits postnatal growth of skeletal muscle is the number of nuclei per muscle fiber. Fiber number is determined by genetic background, while nuclear number is influenced by environmental factors, primarily nutrition and exercise. Further, we have shown that changes in insulin-like growth factors (IGFs) are associated with muscle growth and compensatory hypertrophy. These IGFs may be responsible for mediating the effects of nutrition and exercise on muscle recovery.
The specific aims of this research are: 1) to characterize the relationship of muscle satellite cell activity and DNA synthesis to serum and tissue levels of IGFs during prolonged food restriction and recovery; 2) to determine the effects of an enriched diet during growth recovery on the endocrine and autocrine/paracrine responses of IGFs and on myogenesis; 3) to determine the effects of exercise-induced hypertrophy on expression of muscle IGF mRNA compared with endocrine responses (liver and serum) of IGFs and the IGF binding proteins; and 4) to determine the effects of exogenous growth hormone on liver and muscle expression of IGF mRNA and muscle growth recovery. We have developed an animal model, which produces growth retardation via food restriction, to study the effects of diet and exercise on IGFs during recovery. Rats are used and their food intake restricted to 50% of ad libitum intake from birth to 120 days of age. This restriction results in a 60% growth retardation and a comparable restriction of nuclear proliferation. After 120 days, restricted rats are refed ad libitum. Upon refeeding, animals achieve significant but incomplete growth recovery with muscle weight, fiber cross-sectional area, and total DNA achieving 85% of the levels of age-matched controls. In the proposed studies, we will utilize an enriched diet, exercise and exogenous GH to modify IGFs and enhance muscle recovery.
