%0 Journal Article
%A Sánchez-Ceinos, Julia
%A Guzmán-Ruiz, Rocío
%A Rangel-Zúñiga, Oriol Alberto
%A López-Alcalá, Jaime
%A Moreno-Caño, Elena
%A Del Río-Moreno, Mercedes
%A Romero-Cabrera, Juan Luis
%A Pérez-Martínez, Pablo
%A Maymo-Masip, Elsa
%A Vendrell, Joan
%A Fernández-Veledo, Sonia
%A Fernández-Real, José Manuel
%A Laurencikiene, Jurga
%A Rydén, Mikael
%A Membrives, Antonio
%A Luque, Raul M
%A López-Miranda, José
%A Malagón, María M
%T Impaired mRNA splicing and proteostasis in preadipocytes in obesity-related metabolic disease.
%D 2021
%U https://hdl.handle.net/10668/27857
%X 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.
%K ER-proteostasis
%K ERAD
%K RNA splicing
%K UPR
%K cell biology
%K human
%K obesity-related metabolic diseases
%K preadipocytes
%~