Author, as appears in the article.: Terron-Puig, Margarida; Huber-Ruano, Isabel; Sabadell-Basallote, Joan; Ejarque, Miriam; Nunez-Roa, Catalina; Maymo-Masip, Elsa; Jorba, Rosa; Serena, Carolina; Vendrell, Joan; Fernandez-Veledo, Sonia;
Department: Medicina i Cirurgia Ciències Mèdiques Bàsiques
URV's Author/s: Fernandez Veledo, Sonia / Jorba Martin, Rosa Maria / Maymo Masip, Elsa / Serena Perelló, Carolina / Terrón Puig, Margarida Maria / Vendrell Ortega, Juan José
Keywords: Targeting subunits Sirt6 Sirt1 Senescence Pathways Obesity Metabolism Mesenchymal stem-cells Insulin-resistance Inflammation Glycolysis Glycogen Expression Differentiation Aging Adipose-tissue Adipose-derived mesenchymal stromal cells
Abstract: Dysfunctional adipocyte precursors have emerged as key determinants for obesity- and aging-related inflammation, but the mechanistic basis remains poorly understood. Here, we explored the dysfunctional adipose tissue of elderly and obese individuals focusing on the metabolic and inflammatory state of human adipose-derived mesenchymal stromal cells (hASCs), and on sirtuins, which link metabolism and inflammation. Both obesity and aging impaired the differentiation potential of hASCs but had a different impact on their proliferative capacity. hASCs from elderly individuals (>= 65 years) showed an upregulation of glycolysis-related genes, which was accompanied by increased lactate secretion and glycogen storage, a phenotype that was exaggerated by obesity. Multiplex protein profiling revealed that the metabolic switch to glycogenesis was associated with a pro-inflammatory secretome concomitant with a decrease in the protein expression of SIRT1 and SIRT6. siRNA-mediated knockdown of SIRT1 and SIRT6 in hASCs from lean adults increased the expression of pro-inflammatory and glycolysis-related markers, and enforced glycogen deposition by overexpression of protein targeting to glycogen (PTG) led to a downregulation of SIRT1/6 protein levels, mimicking the inflammatory state of hASCs from elderly subjects. Overall, our data point to a glycogen-SIRT1/6 signaling axis as a driver of age-related inflammation in adipocyte precursors.
Thematic Areas: Medicina veterinaria Geriatrics & gerontology Ciências biológicas ii Ciências biológicas i Cell biology Biotecnología Aging
licence for use: https://creativecommons.org/licenses/by/3.0/es/
Author's mail: carolina.serena@urv.cat elsa.maymo@urv.cat margaridamaria.terron@estudiants.urv.cat sonia.fernandez@urv.cat juanjose.vendrell@urv.cat rosamaria.jorba@urv.cat
Author identifier: 0000-0002-9133-3120 0000-0003-2906-3788 0000-0002-6994-6115 0000-0003-3307-4340
Record's date: 2024-09-07
Papper version: info:eu-repo/semantics/publishedVersion
Link to the original source: https://onlinelibrary.wiley.com/doi/full/10.1111/acel.13667
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Papper original source: Aging Cell. 21 (8):
APA: Terron-Puig, Margarida; Huber-Ruano, Isabel; Sabadell-Basallote, Joan; Ejarque, Miriam; Nunez-Roa, Catalina; Maymo-Masip, Elsa; Jorba, Rosa; Serena, C (2022). Glycogen accumulation in adipocyte precursors from elderly and obese subjects triggers inflammation via SIRT1/6 signaling. Aging Cell, 21(8), -. DOI: 10.1111/acel.13667
Article's DOI: 10.1111/acel.13667
Entity: Universitat Rovira i Virgili
Journal publication year: 2022
Publication Type: Journal Publications
Repositori URV