Quantification of Physiological Adaptations During Altered Loading States in Rodents

Muscle unloading due to space travel, bed rest, or immobilization leads to many physiological adaptations at the whole‐body, tissue, and cellular levels. Specifically, hindlimb suspension unloading (HSU) has been devised as a highly effective technique to simulate the effects of microgravity that lead to muscle atrophy, as well as metabolic and endocrine changes. To quantify metabolic adaptations at various levels, we administered a single bolus of “doubly‐labeled” water (Bederman et al, 2006) to determine: (a) energy expenditure and body composition (whole‐body level); (b) turnover rates of tissue‐specific lipids and proteins from the labeling patterns of protein‐bound alanine and triglyceride‐bound glycerol, rates of de novo lipogenesis, (tissue and cellular level); and (c) labeling patterns of pathway specific metabolites (cellular level). Here, we present the application of this novel methodology in a model of muscle disuse. After three weeks of HSU, rats demonstrated changes at the whole body level (elevated VO2 and VCO2 (lower RQ) and leaner body composition). We report on the changes in fuel selection and rates of tissue remodeling using biochemical fluxes of proteins and lipids. Our work provides the experimental basis for multiscale modeling of the metabolic adaptations to altered loading states.