Cancer cachexia is the rapid, drastic loss of muscle mass associated with cancer and is not reversible by conventional nutritional means (Brown et al., 2018; Brown et al., 2017). It occurs in ~80% of cancer patients and is responsible for 20-40% of cancer-related deaths (Brown et al., 2018; Brown et al., 2017). This condition leaves patients with fatigue, functional impairment, reduced quality of life, and a decrease in survival rates. Cachexia occurs through an imbalance between protein degradation and protein synthesis (Brown et al., 2018), which is associated with inflammation and altered metabolic processes. Several studies have investigated the effects of leucine on cancer cachexia, as it is known for promoting muscle growth through the stimulation of anabolic signaling cascades while inhibiting catabolism. These studies have all been conducted for a short period of time and have shown promise for leucine as a treatment for cancer cachexia. However, one study found that long-term (6 weeks) leucine supplementation increased epididymal fat mass while decreasing muscle mass in rats fed a high-fat diet (Baum et al., 2016). In addition, Lee et al. (2019) demonstrated exacerbated atrophy in tumor-bearing mice after 28 days of low-dose leucine supplementation. Whether leucine is a viable long-term treatment for cancer cachexia requires further investigation. 10 C57BL/6 (WT) mice and 7 APCMin/+ (APC) mice were used in this study and given either tap water as a control or given 1.5% leucine-enriched water. Tissue harvest was conducted at ~24 weeks of age for genetic and western blot analysis. There was a main effect of genotype for decreased body and plantaris weight in APC mice compared to WT (p < 0.05), and a main effect of leucine for lower plantaris weight/tibia length in APC mice (p < 0.05), which appeared to be driven by the APC Min/+ genotype (p = 0.0841). Cyclin D1 mRNA abundance was ~2-fold greater in APC mice compared to WT, although no difference was found with treatment. No difference was found in MyoD or Myogenin mRNA abundance. Long-term leucine supplementation appears to exacerbate atrophy, which appeared to be independent of protein turnover or myogenesis disruption.

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Skeletal muscle has an exceptional ability to regenerate from damage. Still, regenerative capacity can be exceeded with extreme tissue loss, also known as volumetric muscle loss (VML). Causes of VML include munition explosions and excision of tumors (i.e. sarcomas). Patients suffering from VML do not fully recover force output in the affected limb. Adequate interventions have not been established to fully reverse this loss of function. Recent studies show that replacement tissue (i.e. autograph) into the VML defect site plus external growth stimuli (i.e. physical activity) show promise for optimizing force recovery following VML injury.PURPOSEThe purpose of this study is to evaluate the role of physical activity on force output in rats with autographs following VML injury.METHODSSixteen Sprague‐Dawley rats underwent VML. VML was caused by removing a defect equaling 20% of the left tibialis anterior (LTA) weight from the middle portion of the muscle. The defect was sutured back in to the defect site (autograph) shortly after removal. The right TA (RTA) acted as a contralateral control. For the week following VML surgery, wheels were locked for all rats to allow recovery from injury. At the end of that week (2 weeks post‐injury), wheels were unlocked for eight rats which were given ad libitum access whereas the wheel remained locked for the other eight rats and were allowed only normal cage activity. Within the wheel activity (WA) and cage activity (CA) groups, rats were divided into 2 week and 8 week groups (2WA, 2CA, 8WA, 8CA). At either two or eight weeks post‐VML, TAs were harvested. All animals underwent electrophysiology immediately before harvest. Tenotomy of the distal extensor digitalis longus and extensor halluces longus allowed for isolation of maximal isometric force of the TA. Tissue was processed for histology to analyze cross‐sectional area (CSA). Student's t‐test was conducted on all variables.RESULTSIn the 2WA group, force output in the LTA (1.8 N/kg ± .17 SE) was 67% of the RTA (2.7 N/kg ± .09 SE) (p < 0.05). In the 2CA group, force output in the LTA (1.1 N/kg ± .14 SE) was 41% of the RTA (2.7 N/kg ± .15 SE) (p < 0.05). In the 8WA group, force output of the LTA (2.1 N/kg ± .12 SE) was 69.5% of the RTA (3.0 N/kg ± .30 SE) (p < 0.05). In the 8CA, force output of the LTA (2.2 N/kg ± .13 SE) was 75.6% of the RTA (2.9 N/kg ± .04 SE) (p < 0.05). LTA CSA in the 2WA and 2CA was similar between both groups (1012 μm2 ± 54.1 and 1135 μm2 ± 204.1, respectively). Similarly, LTA CSA in the 8WA and 8CA was similar between both groups (1279 μm2 ± 17.8 and 1266 μm2 ± 58, respectively).CONCLUSIONIncorporation of physical activity increases force output at an earlier stage (2 weeks) than normal cage activity; however, continued physical activity does not promote additional force recovery at a later time point (8 weeks) as force output is similar between WA and CA groups.Support or Funding InformationThis study was funded by NIH R15AR064481This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.