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. 2021 Feb 4;11:570170. doi: 10.3389/fphys.2020.570170

TABLE 1.

Studies published in the last 10 years with experimental rat and mouse models.

Author Animal/culture
Cachexia markers Exercise training protocol
Main results
Species/lineage Induction method Type Protocol Volume/intensity
Ballaro et al. (2019) Female BALB/c mice 5 × 105, C26 tumor cells ↓ Total body mass ↓ Muscle mass ↓ Adipose tissue mass Aerobic training Moderate exercise on treadmill Running speed by 11 m/min for 45 min • Exercise-induced a decrease in muscle autophagy markers
• Exercise improves mitochondrial mass and activity in skeletal muscle
• Exercise reduces muscle gene expression of MuRF1 and Atrogin-1
Ranjbar et al. (2019) Balb/c mice 5 × 105 C26 carcinoma cells ↓Body weight ↓Muscle weight ↓Functional capacity Combined training 1° Resistance Training (ladder protocol) and; 2° aerobic training (motorized Wheel), on the same day 4 days/week, 4 weeks before and 11 days after tumor implantation RT - 3 sets of 2 repetitions at 50% of animal body weight AT - 25 min. 5–9 m/min speed • Exercise does not restore body weight loss
• Exercise does not prevent gastrocnemius loss but increase tibialis anterior weight
• Training was able to reduce autophagy markers in muscle
• Exercise does not decrease atrophy markers
Alves et al. (2018) C57BL/6 106 LLC cells No control group was presented to indicate presence of cachexia High-intensity interval training (HIIT) Treadmill running Each session consisted of 5 intervals of 3 min running at 18 m min–1 followed by 4 min running at 25 m min–1 • Decrease on tumor size in tumor trained group
• Increase on PDL1 and VEGF expression in tumor
• Increase of survival
Das Neves et al. (2016) Wistar rats 106, Walker 256 tumor cells injected in the bone marrow Muscle atrophy, inflammatory markers (TNFα) Resistance training (RT) Hind limb (i.e., “squat-like” movement). Started after tumor injection with daily sessions for 15 days 1–3 sets; 10–15 rep; 65% 1RM • Cancer-induced not effect on total body mass
• Muscle atrophy with no changes in RT group
• No difference in atrophy markers
• Loss of strength associated with decrease on survival
Khamoui et al. (2016) Female Balb/c mice 5.0 × 105, C26 tumor cells ↓ Total body mass, muscle and fat mass ↓ Physical function Resistance and aerobic training Training started 8 weeks before tumor injection and during 3 weeks after tumor injection RT was performed on a climb ladder AT in a motorized wheels • RT—3 days per week, 5 sets of 3 repetitions with progressive loads
• AT—60 min, 5 days per week. Speed between 5–6.5 m/min
• RT and AT not restore total and lean or fat mass in C26 group •↑ In IGF-1 gene expression in muscle of RT-C26 and AT-C26 •↑ In Myogenin gene expression in muscle of RT-C26 group
• No differences in physical function in trained groups
Pigna et al. (2016) Female BALB/c mice Grafting of 0.5 mm3 fragment of colon carcinoma (C26) ↓ Total body mass ↓ Muscle mass Aerobic training Wheel-running activity Running for 20:59 ± 4:30 (h min) a day at Speed by 2.1 ± 0.1 (km/h) • Increase in life span in wheel running C26-bearing mice
• Exercise-induced muscle hypertrophy in C26-bearing mice
• Exercise-induced a decrease in muscle autophagy markers
• Exercise reduces muscle gene expression of MuRF1 and Atrogin-1
Pedersen et al. (2016) Female C57BL/6 and NMRI-Foxn1nu mice 2 × 105 B16F10 melanoma cells 2 × 105 LLC tumor cells ↓Body weight ↑Inflammation Running wheels Voluntary running, started 4 weeks prior to tumor cell inoculation Only total running distance was evaluated • Running decrease tumor growth
• Upregulation of pathways associated with immune function
• Levels of epinephrine and IL-6 are related to tumor growth through mobilization of NK cells
Pin et al. (2015) Balb/C or C57BL/6 5 × 105 Colon26 or LLC cells ↓ Muscle mass ↓ Physical function ↓Hematocrit content Aerobic training Treadmill Running, 5 days/week, 14 or 28 days after C26 or LLC implantation, respectively Mice ran for 45 min at the speed of 14 m/min • In the C26 hosts, acute exercise does not prevent muscle wasting
• LLC hosts are responsive to exercise and their treatment with the EX-EPO combination prevents the loss of muscle strength
• LLC EX-EPO group increases muscle oxidative capacity
Donatto et al. (2013) Wistar rats Walker 256, 3 × 107 tumor cells ↓ Total body mass ↓ Muscle mass inflammatory markers Resistance training 8 weeks of resistance training, with climbing sessions Training sessions were 3–5 ladder climbs with 75, 90, and 100% of the rat’s previous maximal carrying capacity • RT increased by 9% body weight gain in TB group
• LDL-c levels were decreased with RT in TB group
• HDL-c levels were increased with RT in TB group
• IL-10/TNFα ratio was higher with RT in TB group
• RT attenuate the protein content of IL-6
Lira et al. (2012) Wistar rats Walker-256 carcinosarcoma (2 × 107 cells/rat) ↓Body weight Aerobic training 8 weeks of treadmill running 15–60 min at 10 m/min. Intensity maintained between 60 and 65% VO2 max • Training groups showed decrease on adipose tissue content;
• Decrease on tumor size in tumor trained group
• Exercise tumor group showed decrease of IL-6 MEAT content
• Exercise tumor group showed decrease on IL-10/TNFα ratio in MEAT group
• Decrease of macrophages infiltration on adipose tissue with training
Penna et al. (2011) C57BL/6 mice 5 × 105 LLC cells ↓ Muscle mass ↓ Adipose tissue mass Aerobic training Treadmill running 14 m/min, 45 min, 5 days/week • Exercise + EPA treatment attenuate muscle wasting
• Exercise + EPA improve muscle strength
• Exercise + EPA reduce tumor weight

TNFα, Tumor Necrosis Factor-Alpha; RM, Maximal Repetition; RT, Resistance Training; AT, Aerobic Training; IGF-1, Insulin-Like Growth Factor-1; C26, Colon-26 Adenocarcinoma; MURF-1, Muscle RING-Finger Protein-1 (Murf1); ATROGIN-1, Muscle-Specific Ubiquitin Ligase; EPA, Eicosatetraenoic Acid; LLC, Lewis Lung Carcinoma; TB, Tumor Bearing Group; LDL, Low Density Lipoproteins; HDL, Hight Density Lipoproteins; IL-6, Interleukin Type 6; NK, Natural Killer Cells; PDL-1, Programmed Death-Ligand 1; VEGF, Vascular Endothelial Growth Factor.