Characterization of Adipose Mesenchymal Stromal Cells (ASC) in Aging and Obesity

Identifier:  TDX:4379

Handle: https://hdl.handle.net/20.500.11797/TDX4379

Authors:  Terrón Puig, Margarida Maria

Abstract:
Dysfunctional adipocyte precursors are increasingly recognized as significant contributors to the inflammation associated with aging and obesity, yet the underlying mechanisms remain unclear. Here, we explored the dysfunctional adipose tissue of elderly subjects and individuals with obesity, concentrating on the metabolic alterations in human adipose-derived mesenchymal stromal cells (hASC). These alterations may modify hASC's differentiation potential and immunomodulatory properties. We particularly examined the role of sirtuins as potential mediators bridging metabolism and inflammation. Our findings revealed that while both obesity and aging impaired the differentiation potential of hASC, their effects on proliferative capacity differed. We observed upregulated glycolysis-related genes in hASC from elderly individuals ( 65 years), a phenotype accentuated by obesity. This upregulation corresponded with increased lactate secretion and glycogen storage. Through multiplex protein profiling, we associated the metabolic switch towards glycolysis and glycogenesis with a transformation in the secretome pattern, which implied an elevated secretion of inflammatory-chemotactic and immunosuppressive cytokines. Furthermore, hASC isolated from obese and elderly settings, characterized by increased glycolytic flux and glycogen deposition, demonstrated an increased capacity to suppress T-cell proliferation and promote lymphocyte and monocyte migration. Additionally, these cells could polarize macrophages towards a mixed-M2 phenotype.