Effects of aerobic exercise via Gut-Muscle Axis on sarcopenia and inflammation in CT26 tumor mice
10.3969/j.issn.1000-6710.2025.06.005
- VernacularTitle:有氧运动经肠-肌轴对CT26肿瘤小鼠肌少症及其炎症反应的影响研究
- Author:
Shuling ZHANG
1
;
Junwei WANG
;
Yu QIAN
;
Shiliang HU
;
Junzhi SUN
;
Chun WANG
Author Information
1. 成都体育学院(四川 成都 610041)
- Publication Type:Journal Article
- Keywords:
Gut-Muscle Axis;
aerobic exercise;
CT26 tumor;
sarcopenia;
inflammation
- From:
Chinese Journal of Sports Medicine
2025;44(6):466-482
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effect of aerobic exercise on sarcopenia in CT26 tumor mice through the gut microbiota-skeletal muscle axis and its potential mechanism.Methods Forty-eight SPF BALB/c male mice aged 8 weeks were randomly divided into a normal control group(group NC,n=12),a normal control+aerobic exercise group(group NA,n=12),a CT26 tumor-associated sarco-penia group(group TS,n=12)and a CT26 tumor-associated sarcopenia+aerobic exercise group(group TSA,n=12).After a 2-week adaptive exercise period,CT26 cell suspension(0.2 mL,1×107 cells/mL)was subcutaneously injected into the dorsal region of mice in group TS and group TSA,while group NC and group NA were inoculated with 0.2 mL normal saline.One day later,group NA and group TSA underwent a 4-week aerobic treadmill running intervention(14 m/min,60 min/day,6 days/week).If a mouse failed to complete the target intensity on a given day,its running speed was reduced by 20%the following day.Moreover,group NA and group TSA received no exercise interven-tion.General health status of all groups was monitored throughout the study.The forelimb gripping force,rotarod walking time and the cross-sectional area of gastrocnemius muscle fibers were measured.Moreover,the ultrastructural changes of gastrocnemius were observed by transmission electron micro-scope,while the cecum contents were observed by 16S rRNA sequencing.Meanwhile,the pathological morphological changes of small intestine wall were observed using HE,while the contents of tumor ne-crosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-1β(IL-1β)and lipopoly saccharide(LPS)of serum and gastrocnemius muscle were determined by using ELISA.Moreover,small intestine zonula occludens-1(ZO-1),Occludin and muscle ring finger 1(MuRF1),muscle atrophy F-box(MAF-bx),Toll-like receptor 4(TLR4)/myeloid differentiation factor 8(MyD88)/nuclear transcription factor-κB(NF-κB)signal pathway related proteins expression levels of gastrocnemius muscle,as well as muscle ring finger 1(MuRF1)and muscle atrophy F-box(MAF-bx)were detected using Western blot.Results(1)Subcutaneous tumors were prominent in group TS.The forelimb gripforce,wet weight and cross-sectional area of gastrocnemius,and rotarod walking time in group TS at the 5th and 6th weekends were significantly lower than group NC(P<0.01),while the relative expression levels of MuRF1 and MAF-bx proteins in the gastrocnemius muscle in group TS were significantly higher than the latter group(P<0.05,P<0.01).Moreover,transmission electron microscopy revealed sparse and dis-organized muscle fiber arrangement in group TS,with visible Z-lines but indistinct M-lines,as well as shortened,poorly defined,and thin sarcomeres.(2)The group TSA exhibited significantly higher α-diversity indices(Shannon,Chao1,and Observed species)in gut microbiota compared to group TS(P<0.05,P<0.01,P<0.05),while the β-diversity differed to some extent between the two groups.At phylum level,the F/B ratio was lower in group NA than that group NC,with that of group TSA low-er than group TS.At genus level,the relative abundances of Muribaculaceae,Bacteroides,Roseburia,and Alistipes in group NA were higher than group NC,and those of Alloprevotellaand Helicobacter were significantly lower,while those of Muribaculaceae,Lachnospiraceae_NK4A136_group,Roseburia,Bacteroides,Lachnospiraceae_UCG-001 of group TSA were significantly higher than group TS.Nota-bly,Roseburia and Alistipes were the most significantly enriched genera in group TSA and group TS(LDA score>4 for both).(3)The inflammatory cells of the small intestine wall in group TSA signifi-cantly reduced than those in group TS(P<0.05).Moreover,the expression level of ZO-1 proteins in the small intestine wall were significantly higher in group NA than group NC,and that of ZO-1 and Occludin proteins in the small intestine wall was significantly higher in group TSA than those in group TS(P<0.05).(4)The group NA exhibited significantly lower LPS concentrations in the gastrocne-mius muscle compared to group NC(P<0.05).Similarly,the group TSA showed reduced LPS levels in both serum and gastrocnemius compared to group TS(P<0.05).The relative protein expression of p-IκBα and p-NF-κB p65 significantly decreased in group TSA compared to group TS(P<0.05).The group TS displayed elevated concentrations of pro-inflammatory cytokines(TNF-α,IL-1β)in serum and gastrocnemius compared to group NC(P<0.01,P<0.05).The group TSA demonstrated significantly lower levels of TNF-α and IL-6 in these tissues in comparison with group TS(P<0.05,P<0.01).Conclusion Aerobic exercise can improve gut microbiota α diversity,adjusting its composition,improv-ing intestinal mucosal barrier function,reducing the LPS-induced pro-inflammatory response,and delay-ing skeletal muscle atrophy.The underlying mechanism may involve down regulation of TLR4/MyD88/NF-κB signaling in skeletal muscle,which has a positive effect on Gut-Muscle Axis.
