Author, as appears in the article.: Sánchez-Ceinos J; Guzmán-Ruiz R; Rangel-Zúñiga OA; López-Alcalá J; Moreno-Caño E; Del Río-Moreno M; Romero-Cabrera JL; Pérez-Martínez P; Maymo-Masip E; Vendrell J; Fernández-Veledo S; Fernández-Real JM; Laurencikiene J; Rydén M; Membrives A; Luque RM; López-Miranda J; Malagón MM
Department: Medicina i Cirurgia Bioquímica i Biotecnologia
URV's Author/s: Fernandez Veledo, Sonia / Maymo Masip, Elsa / Vendrell Ortega, Juan José
Keywords: Preadipocytes Human adipose-tissue upr tool stress rna splicing obesity-related metabolic diseases insulin-resistance human adipocytes human homeostasis fat erad er-proteostasis differentiation cells adipogenesis
Abstract: Preadipocytes are crucial for healthy adipose tissue expansion. Preadipocyte differentiation is altered in obese individuals, which has been proposed to contribute to obesity-associated metabolic disturbances. Here, we aimed at identifying the pathogenic processes underlying impaired adipocyte differentiation in obese individuals with insulin resistance (IR)/type 2 diabetes (T2D). We report that down-regulation of a key member of the major spliceosome, PRFP8/PRP8, as observed in IR/T2D preadipocytes from subcutaneous (SC) fat, prevented adipogenesis by altering both the expression and splicing patterns of adipogenic transcription factors and lipid droplet-related proteins, while adipocyte differentiation was restored upon recovery of PRFP8/PRP8 normal levels. Adipocyte differentiation was also compromised under conditions of endoplasmic reticulum (ER)-associated protein degradation (ERAD) hyperactivation, as occurs in SC and omental (OM) preadipocytes in IR/T2D obesity. Thus, targeting mRNA splicing and ER proteostasis in preadipocytes could improve adipose tissue function and thus contribute to metabolic health in obese individuals.
Thematic Areas: Saúde coletiva Química Nutrição Neuroscience (miscellaneous) Neuroscience (all) Medicine (miscellaneous) Medicina veterinaria Medicina ii Medicina i Interdisciplinar Immunology and microbiology (miscellaneous) Immunology and microbiology (all) Geografía Geociências General neuroscience General medicine General immunology and microbiology General biochemistry,genetics and molecular biology Farmacia Educação física Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciências agrárias i Biotecnología Biology Biodiversidade Biochemistry, genetics and molecular biology (miscellaneous) Biochemistry, genetics and molecular biology (all) Astronomia / física
licence for use: https://creativecommons.org/licenses/by/3.0/es/
Author's mail: sonia.fernandez@urv.cat elsa.maymo@urv.cat juanjose.vendrell@urv.cat
Author identifier: 0000-0003-2906-3788 0000-0002-9133-3120 0000-0002-6994-6115
Record's date: 2024-07-27
Papper version: info:eu-repo/semantics/publishedVersion
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Papper original source: Elife. 10
APA: Sánchez-Ceinos J; Guzmán-Ruiz R; Rangel-Zúñiga OA; López-Alcalá J; Moreno-Caño E; Del Río-Moreno M; Romero-Cabrera JL; Pérez-Martínez P; Maymo-Masip E (2021). Impaired mRNA splicing and proteostasis in preadipocytes in obesity related metabolic disease. Elife, 10(), -. DOI: 10.7554/eLife.65996
Entity: Universitat Rovira i Virgili
Journal publication year: 2021
Publication Type: Journal Publications
Repositori URV