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Sánchez-Ceinos, Julia; Guzmán-Ruiz, Rocío; Rangel-Zúñiga, Oriol Alberto; López-Alcalá, Jaime; Moreno-Caño, Elena; Del Río-Moreno, Mercedes; Romero-Cabrera, Juan Luis; Pérez-Martínez, Pablo; Maymo-Masip, Elsa; Vendrell, Joan; Fernández-Veledo, Sonia; Fernández-Real, José Manuel; Laurencikiene, Jurga; Rydén, Mikael; Membrives, Antonio; Luque, Raul M; López-Miranda, José; Malagón, María M
eLife, 09/2021, Letnik: 10Journal Article
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.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Vir: Osebne bibliografije
in: SICRIS
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