Comparable Organ Protein Fractional Synthesis Rate of High and Low-Active Mice

Abstract

Abstract Objectives With the rise in physical inactivity and its related diseases, it is necessary to understand the mechanisms involved in physical activity regulation. Scientists have explored physical activity regulation by investigating various physiological mechanisms involving hormones, neurotransmitters, and genetics; however, little is known about the role of metabolism on physical activity level. We hypothesize that protein turnover in specific organs like the muscle is higher in mice previously exhibiting high physical activity levels, as a mechanism to adapt to the increased demand. Therefore, we studied protein fractional synthesis rate (FSR) in tissues of inherently high and low active mice. Methods In order to study protein FSR of various organs, we assessed 12-week-old male inherently low-active (LA) mice (n = 23, lean body mass: 21.0 ± 1.1 g, C3H/HeJ strain) and high active (HA) mice (n = 20, lean body mass: 22.5 ± 1.3, C57L/J strain). One day before tissue collection, a D2O bolus was administered via intraperitoneal injection, and mice were provided D2O enriched drinking water to enrich the total body water to about 5% D2O. Eleven tissues (kidney, heart, lung, muscle, fat, jejunum, ileum, liver, brain, skin, and bone) were collected and analyzed for enrichment of alanine in the intracellular and protein-bound pool (LC-MS/MS). FSR was calculated as -ln(1-enrichment) as fraction per day. Data are mean ± SE (unpaired t-test: GraphPad Prism 8.2). Results We did not find significant differences between protein FSR of HA and LA mice in any measured organ. Example: Protein FSR (fraction/day): muscle (LA: 0.0326±-0.0026, HA: 0.0331 ± 0.0018, P = 0.8673), liver (0.3568 ± 0.0219, 0.3499 ± 0.0217, P = 0.8263), brain (0.0981 ± 0.0056, 0.1041 ± 0.0063, P = 0.4758). Conclusions The observed lack of significant differences in high and low-active mice suggests that differences in specific organ tissue protein turnover may not be a mechanism regulating inherent physical activity level. Since protein turnover is representative of the ability to adapt through upregulation and downregulation of metabolic processes, these results show that high-active mice are inherently no more equipped for metabolic regulation than the low active mice. Funding Sources Sydney and J.L. Huffines Institute for Sports Medicine, Human Performance Student Research Grant and CTRAL Grant.