人体不同部位白色脂肪细胞衰老的异质性OA

Objective:To delineate depot-specific features of senescence in human subcutaneous mature adipocytes and to compare how adipocytes from different anatomical sites respond to pro-senescent stimuli.Methods:Publicly available transcriptomic datasets were firstly analyzed to compare the gene expression patterns between isolated adipocytes and whole adipose tissue.Subcutaneous fat was collected from human chest,abdomen,and thigh,and mature adipocytes were isolated.Senescence in vivo was evaluated by senescence-associated β-galactosidase(SA-β-gal)staining and quantitative PCR analysis of senescence-associated genes including cyclin-dependent kinase inhibitor 1A(CDKN1A),cyclin D1(CCND1),and tumor protein p53(TP53).For in vitro modeling of obesity-relevant stress,adipocytes were cultured in medium supplemented with 10%fetal bovine serum for 4-7 d;cell-cycle re-entry(EdU incorporation),senescence markers,and senescence-associated secretory phenotype(SASP)factors interleukin-1β(IL-1β)and matrix metalloproteinase 14(MMP14)were then measured.Results:Senescence-associated markers were more prominent in mature adipocytes than in whole adipose tissue.Among non-obese individuals,thigh adipocytes displayed the earliest senescence features,with higher SA-β-gal activity and increased expression of CDKN1A and CCND1.After serum exposure,chest adipocytes exhibited the strongest response,characterized by a higher frequency of cell-cycle re-entry and greater induction of senescence markers and inflammatory/pro-fibrotic factors,including IL-1β and MMP14,than abdominal or thigh adipocytes.Conclusions:Subcutaneous adipocyte senescence displays clear depot specificity.Thigh adipocytes show earlier senescence features,whereas chest adipocytes are more responsive to obesity-related stimulation.This spatiotemporal heterogeneity may play an important role in metabolic regulation and development of obesity-associated diseases,including breast cancer.