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 mRNA
K1 Proteostasis
K1 Adipocytes
K1 Obesity
K1 Metabolic disease
K1 Tissue expansion
K1 ARN mensajero
K1 Adipocitos
K1 Obesidad
K1 Enfermedades metabólicas
K1 Expansión de tejido
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.
PB eLife Sciences Publications
YR 2021
FD 2021-09-21
LK http://hdl.handle.net/10668/4480
UL http://hdl.handle.net/10668/4480
LA en
NO Sánchez-Ceinos J, Guzmán-Ruiz R, Rangel-Zúñiga OA, López-Alcalá J, Moreno-Caño E, Del Río-Moreno M, et al. Impaired mRNA splicing and proteostasis in preadipocytes in obesity-related metabolic disease. Elife. 2021 Sep 21;10:e65996
DS RISalud
RD Apr 18, 2025