Author, as appears in the article.: Sanchez-Ceinos, Julia; Guzman-Ruiz, Rocio; Alberto Rangel-Zuniga, Oriol; Lopez-Alcala, Jaime; Moreno-Cano, Elena; Del Rio-Moreno, Mercedes; Luis Romero-Cabrera, Juan; Perez-Martinez, Pablo; Maymo-Masip, Elsa; Vendrell, Joan; Fernandez-Veledo, Sonia; Manuel Fernandez-Real, Jose; Laurencikiene, Jurga; Ryden, Mikael; Membrives, Antonio; Luque, Raul M; Lopez-Miranda, Jose; Malagon, Maria M
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: elsa.maymo@urv.cat; sonia.fernandez@urv.cat; jvortega@iispv.cat
Record's date: 2025-02-01
Paper version: info:eu-repo/semantics/publishedVersion
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Paper original source: Elife. 10 e65996-
APA: Sanchez-Ceinos, Julia; Guzman-Ruiz, Rocio; Alberto Rangel-Zuniga, Oriol; Lopez-Alcala, Jaime; Moreno-Cano, Elena; Del Rio-Moreno, Mercedes; Luis Romer (2021). Impaired mRNA splicing and proteostasis in preadipocytes in obesity related metabolic disease. Elife, 10(), e65996-. DOI: 10.7554/eLife.65996
Article's DOI: 10.7554/eLife.65996
Entity: Universitat Rovira i Virgili
Journal publication year: 2021
Publication Type: Journal Publications
Repositori URV