Author(s): YAN, Y., DONGGUAN, J., Institution: BEIJING SPORT UNIVERSITY, Country: CHINA, Abstract-ID: 2793

INTRODUCTION:
Adipose tissue fibrosis is a crucial pathological feature of age-related functional decline in adipose tissue, which can exacerbate metabolic disorders and promote systemic aging. Using the senescence-accelerated mouse model SAMP8, this study first aimed to identify the critical time points for adipose tissue aging and fibrosis development and screen for underlying molecular mechanisms at the transcriptomic level. Furthermore, it investigated the interventional effects of moderate-intensity aerobic exercise on subcutaneous adipose tissue fibrosis during aging and the potential signaling pathways involved, providing experimental evidence for exercise in delaying adipose tissue aging and associated fibrosis.
METHODS:
During the aging process of SAMP8 male mice, the senescence score, body weight and relative weight of subcutaneous adipose tissue were measured at 2, 4, 6, 8, 10 and 12 months of age. Subcutaneous adipose tissues pf each age were collected for aging, fibrosis phenotype detected. Transcriptome sequencing, time-series clustering, and KEGG pathway enrichment analysis were conducted on subcutaneous adipose tissue from 2-, 8-, and 12-month-old mice. Then 2, 7-month-old male SAMP8 mice were randomly assigned to a sedentary control group (Con) or an aerobic exercise group (Ex), undergoing 8 weeks of moderate-intensity treadmill training(MICT). Differences between groups were compared regarding body weight, relative subcutaneous adipose tissue weight, senescence and fibrosis phenotypes, and the mRNA and protein expression of Neu1/ALK5-Smad2/3 pathway components.
RESULTS:
Compared to the 2-month group, 8-month groups showed significantly increased senescence scores (P<0.01), higher positive rates of p16 and p21 in subcutaneous adipose tissue (P<0.01), aggravated collagen fiber deposition (P<0.01), upregulated mRNA expression of Sma, Col6α1, and Timp1 (P<0.05) , downregulated Mmp9 expression (P<0.05). Transcriptome sequencing and time-series clustering analysis showed that the C4 gene cluster expression continuously increased with age, with the sialidase-encoding gene Neu1 significantly highly expressed at 8 and 12 months. After 8-weeks MICT, the relative weight of subcutaneous adipose tissue, the positive expression rates of p16 and p21, and the area of collagen deposition in the mice of the exercise group were significantly reduced (P < 0.05). The expressions of fibrosis-related genes Sma and Col6α1 were significantly downregulated (P < 0.05), the expression of Mmp9 was significantly upregulated (P < 0.05), and the mRNA expressions of Neu1, Tgfbr1, and the protein expressions of NEU1, ALK5, and p-Smad2 were all significantly decreased (P < 0.05).
CONCLUSION:
8-months is the key time point for the occurrence and development of age-related fibrosis in adipose tissue. 8-weeks MICT can effectively delay the process of fat aging by down-regulating the expression level of the NEU1/ALK5-Smad2/3 pathway in subcutaneous adipose tissue.