Energy metabolism pathways in rat muscle under conditions of simulated microgravity

Abstract

Evidence from rats flown in space suggests that there is a decrease in the ability of the soleus muscle to oxidize long chain fatty acids during space flight. The observation suggests that a shift in the pathways involved in muscle fuel utilization in the absence of load on the muscle has occurred. It is also possible that the reduction is part of a general down-sizing of metabolic capacity since energy needs of inactive muscle are necessarily less. The rodent hind limb suspension model has proved to be a useful ground based model for studying the musculo-skeletal systems changes that occur with space flight. Microarray technology permits the screening of a large number of the enzymes of the relevant pathways thereby permitting a distinction to be made between a shift fuel utilization pattern or a general decrease in metabolic activity. The soleus muscle was isolated from 5 control and 5 hindlimb suspended rats (21 days) and the Affymetrix system for assessing gene expression used to determine the impact of hindlimb unloading on fuel pathways within the muscle of each animal. Results: Suspended rats failed to gain weight at the same rate as the controls (337 ± 5 g vs 318 ± 6 g, p < 0.05) and muscle mass from the soleus was reduced (135 ± 3 mg vs 48 ± 4 mg, p < 0.05). There was a consistent decrease (p < 0.05) in gene expression of proteins involved in fatty acid oxidation in the suspended group whereas glycolytic activity was increased (p < 0.05). Gene expressions of individual key regulatory enzymes reflected these changes. Carnitine palmitoyltransferase I and II were decreased (p < 0.05) whereas expression of hexokinase, phosphofructokinase and pyruvate kinase were increased (p < 0.05). Conclusion: Disuse atrophy is associated with a change in mRNA levels of enzymes involved in fuel metabolism indicative of a shift in substrate utilization away from fat towards glucose.