Autor según el artículo: 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;
Departamento: Medicina i Cirurgia Ciències Mèdiques Bàsiques
Autor/es de la URV: Fernandez Veledo, Sonia / Jorba Martin, Rosa Maria / Maymo Masip, Elsa / Serena Perelló, Carolina / Terrón Puig, Margarida Maria / Vendrell Ortega, Juan José
Palabras clave: 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
Resumen: 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.
Áreas temáticas: Medicina veterinaria Geriatrics & gerontology Ciências biológicas ii Ciências biológicas i Cell biology Biotecnología Aging
Acceso a la licencia de uso: https://creativecommons.org/licenses/by/3.0/es/
Direcció de correo del autor: 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
Identificador del autor: 0000-0002-9133-3120 0000-0003-2906-3788 0000-0002-6994-6115 0000-0003-3307-4340
Fecha de alta del registro: 2024-09-07
Versión del articulo depositado: info:eu-repo/semantics/publishedVersion
Enlace a la fuente original: https://onlinelibrary.wiley.com/doi/full/10.1111/acel.13667
URL Documento de licencia: https://repositori.urv.cat/ca/proteccio-de-dades/
Referencia al articulo segun fuente origial: Aging Cell. 21 (8):
Referencia de l'ítem segons les normes 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
DOI del artículo: 10.1111/acel.13667
Entidad: Universitat Rovira i Virgili
Año de publicación de la revista: 2022
Tipo de publicación: Journal Publications