Research

A computational model of skeletal muscle metabolism linking cellular adaptations induced by altered loading states to metabolic responses during exercise

Ranjan K Dash^3,4,5* , John A DiBella II^1* and Marco E Cabrera^1,2,3,4

¹  Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA

²  Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, USA

³  Department of Pediatrics, Case Western Reserve University, Cleveland, OH, USA

⁴  Center for Modeling Integrated Metabolic Systems, Case Western Reserve University, Cleveland, OH, USA

⁵  Biotechnology and Bioengineering Center, Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA

author email corresponding author email* Contributed equally

BioMedical Engineering OnLine 2007, 6:14doi:10.1186/1475-925X-6-14

Published:	20 April 2007

Abstract

Background

The alterations in skeletal muscle structure and function after prolonged periods of unloading are initiated by the chronic lack of mechanical stimulus of sufficient intensity, which is the result of a series of biochemical and metabolic interactions spanning from cellular to tissue/organ level. Reduced activation of skeletal muscle alters the gene expression of myosin heavy chain isoforms to meet the functional demands of reduced mechanical load, which results in muscle atrophy and reduced capacity to process fatty acids. In contrast, chronic loading results in the opposite pattern of adaptations.

Methods

To quantify interactions among cellular and skeletal muscle metabolic adaptations, and to predict metabolic responses to exercise after periods of altered loading states, we develop a computational model of skeletal muscle metabolism. The governing model equations – with parameters characterizing chronic loading/unloading states- were solved numerically to simulate metabolic responses to moderate intensity exercise (WR ≤ 40% VO_{2 max}).

Results

Model simulations showed that carbohydrate oxidation was 8.5% greater in chronically unloaded muscle compared with the loaded muscle (0.69 vs. 0.63 mmol/min), while fat oxidation was 7% higher in chronically loaded muscle (0.14 vs. 0.13 mmol/min), during exercise. Muscle oxygen uptake (VO₂) and blood flow (Q) response times were 29% and 44% shorter in chronically loaded muscle (0.4 vs. 0.56 min for VO₂ and 0.25 vs. 0.45 min for Q).

Conclusion

The present model can be applied to test complex hypotheses during exercise involving the integration and control of metabolic processes at various organizational levels (cellular to tissue) in individuals who have undergone periods of chronic loading or unloading.