Effects Of High-intensity Interval Training On Senescence-related Secretory Phenotypes And MiRNAs Expression In Adipose Tissue Of Aging Rats

Objective:To investigate the effects and mechanism of high-intensive interval training(HIIT)on senescence-associated secretory phenotype(SASP)in adipose tissue of aging rats.Methods:36 female Sprague Dawley rats at 18 months old were selected randomly and divided into three groups:sedentary control(SED),moderate-intensity continuous training(MICT),and high-intensity interval training group(HIIT),12 rats per group.HIIT group started with a speed of 15 m/min and lasted for 4 min.After that,the high-intensity training speed was 25 m/min,and the time was 1 min.Then,9 cycles were successively alternated.The MICT group had a speed of 17 m/min and a time of45 min.The exercise lasted eight months.Expression of p16-INK4a,p53,adiponectin,leptin,interleukin-6(IL-6),interleukin-1?(IL-1?)and monocyte chemoattractant protein-1(MCP-1)in visceral adipose tissue was detected by western blot and RT-PCR Immunohistochemistry was used to examine the morphology of visceral adipocytes,the contents of beta-galactosidase and p16-INK4a.The expressions of miR-29a,miR-34a,miR-15b,miR-23a,miR-146a,miR-146b,miR-155,miR-130b and miR-124 in adipose tissues were detected by RT-PCR.Western blotting was performed to detect the protein and phosphorylation of NF-B,MAPK and AKT in visceral adipose tissue.Results:Compared with the SED and MICT groups,the average adiponectin cross-sectional area(P<0.01),the number of adiponectin cells(P<0.05)and the expression of IL-6,IL-1,leptin,TNF-?,p16^-INK4a protein and mRNA were significantly decreased in the HIIT group(P<0.01),while the expressions of adiponectin protein(P<0.05)and mRNA were significantly increased in the HIIT group(P<0.01).The expressions of p53 protein and mRNA in HIIT and MICT groups were lower than those in SED group(P<0.01).The expressions of miR-15b,miR-23a,miR-146a,miR-155,miR-130b and miR-124 in HIIT group were higher than those in SED and MICT group(P<0.01).The expressions of miR-21 and miR-126a in HIIT group were significantly lower than those in MICT group(P<0.05).KEGG pathway analysis showed that MICT and HIIT enriched NF-B,PI3K-AKT and MAPK pathways,and MICT enriched TNF-?pathway specifically.WB further verified that the ratios of p-NF-?B,p-MAPK,p-NF-?B/NF-?B and p-MAPK/MAPK in HIIT group were lower than those of SED and MICT group(p<0.01),The expression of p-AKT and p-AKT/AKT was higher than that of SED and MICT(p<0.01).The results of correlation analysis showed that miR-124 was negatively correlated with the contents of p16-INK4a(r=-0.96),TNF-?(r=-0.85),IL-6(r=-0.72)and IL-1(r=-0.71)in adipose tissue.Conclusion:HIIT inhibited SASP secretion in visceral adipose tissue more significantly than MICT,and this process may be related to the expression change of inflamm-aging miRNAs,activation of AKT pathway,and inhibition of NF-B and MAPK pathway.