Protein fractional synthesis rates within tissues of high- and low-active mice

Abstract

With the rise in physical inactivity and its related diseases, it is necessary to understand the mechanisms involved in physical activity regulation. Biological factors regulating physical activity are studied to establish a possible target for improving the physical activity level. However, little is known about the role metabolism plays in physical activity regulation. Therefore, we studied protein fractional synthesis rate (FSR) of multiple organ tissues of 12-week-old male mice that were previously established as inherently low-active (n = 15, C3H/HeJ strain) and high-active (n = 15, C57L/J strain). Total body water of each mouse was enriched to 5% deuterium oxide (D2O) via intraperitoneal injection and maintained with D2O enriched drinking water for about 24 h. Blood samples from the jugular vein and tissues (kidney, heart, lung, muscle, fat, jejunum, ileum, liver, brain, skin, and bone) were collected for enrichment analysis of alanine by LC-MS/MS. Protein FSR was calculated as -ln(1-enrichment). Data are mean±SE as fraction/day (unpaired t-test). Kidney protein FSR in the low-active mice was 7.82% higher than in high-active mice (low-active: 0.1863±0.0018, high-active: 0.1754±0.0028, p = 0.0030). No differences were found in any of the other measured organ tissues. However, all tissues resulted in a generally higher protein FSR in the low-activity mice compared to the high-activity mice (e.g. lung LA: 0.0711±0.0015, HA: 0.0643±0.0020, heart LA: 0.0649± 0.0013 HA: 0.0712±0.0073). Our observations suggest that high-active mice in most organ tissues are no more inherently equipped for metabolic adaptation than low-active mice, but there may be a connection between protein metabolism of kidney tissue and physical activity level. In addition, low-active mice have higher organ-specific baseline protein FSR possibly contributing to the inability to achieve higher physical activity levels.

Protein turnover in pigs: A review of interacting factors

“…Gentry et al (2002) showed no differences in the percentage of muscle fibre types when pigs were reared in long pens with 10 times more space allowance, even though they noticed higher physical activity than those reared in conventional dimensions. Similarly, neither Cross et al (2020) found differences between inherently low‐active and high‐active inbred strain mice; while low‐active mice had a higher kidney FSR. In addition to increased physical activity, access to the outdoors may lead to greater exposure to temperature fluctuations.…”

“…The mechanisms responsible for protein turnover vary for each type of protein, resulting in differences among organs and tissues. There is wide evidence that skeletal musculature has a relatively slow turnover rate in comparison with several visceral organs (Bregendahl et al, 2008; Cross et al, 2020; Garlick et al, 1976; Ten Have et al, 2019). According to Garlick et al (1976), protein FSR of skeletal muscle are 77–86% lower than those of spleen, kidney, liver and lungs, and 47% lower than those of the brain.…”

“…Similarly, skeletal muscle FSR is 76–93% lower than liver and 79–97% than upper gut sections (duodenum and jejunum), taking in consideration the references collected in Table 1 of the present review. In general, jejunum has the highest FSR, followed by liver, ileum, heart and skeletal muscle (Cross et al, 2020). Nevertheless, skeletal muscle is the major contributor to whole‐body protein synthesis in the pig (50%; Huber, Rudar, et al, 2018; Huber, Squires, et al, 2018) as it is the main reservoir of total body mass protein, while the liver contributes about 10% (Garlick et al, 1976).…”

Comparative Analysis of miRNA Expression after Whole-Body Irradiation Across Three Strains of Mice

“…Future murine studies should expand this number to include both males and females of inbred (e.g., CD2F1), and outbred strains (e.g., CD-1), due to their reported differences in radiation sensitivity (75). Additionally, while C3H/HeJ, BALB/c, and C57BL/6 have been reported to exhibit differences in their DNA repair pathways, immune response, protein synthesis rates, and hemostatic conditions (76)(77)(78)(79), studying the effect of each of these factors individually on the miRNA expression could greatly improve our understanding of the RNA response to radiation. Furthermore, although they are beneficial for initial studies, mouse models are inherently limited by their limited translatability to humans.…”

Early Life Androgen Administration Attenuates Aging Related Declines in Muscle Protein Synthesis

“…Calculations. Based on previous work (22), we chose to analyze the true precursor of the incorporation into protein alanine rather than an indirect measurement. We calculated the labeled to unlabeled ratio (tracer-tracee ratio (TTR)) of alanine of each organ tissue and corrected the value with the natural abundance of the tracer.…”