RT Journal Article
T1 Impaired mRNA splicing and proteostasis in preadipocytes in obesity-related metabolic disease.
A1 Sánchez-Ceinos, Julia
A1 Guzmán-Ruiz, Rocío
A1 Rangel-Zúñiga, Oriol Alberto
A1 López-Alcalá, Jaime
A1 Moreno-Caño, Elena
A1 Del Río-Moreno, Mercedes
A1 Romero-Cabrera, Juan Luis
A1 Pérez-Martínez, Pablo
A1 Maymo-Masip, Elsa
A1 Vendrell, Joan
A1 Fernández-Veledo, Sonia
A1 Fernández-Real, José Manuel
A1 Laurencikiene, Jurga
A1 Rydén, Mikael
A1 Membrives, Antonio
A1 Luque, Raul M
A1 López-Miranda, José
A1 Malagón, María M
K1 ER-proteostasis
K1 ERAD
K1 RNA splicing
K1 UPR
K1 cell biology
K1 human
K1 obesity-related metabolic diseases
K1 preadipocytes
AB 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.
YR 2021
FD 2021-09-21
LK https://hdl.handle.net/10668/27857
UL https://hdl.handle.net/10668/27857
LA en
DS RISalud
RD Apr 4, 2025