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Impaired mRNA splicing and proteostasis in preadipocytes in obesity-related metabolic disease

by López-Alcalá, Jaime , Moreno-Caño, Elena , Fernández-Real, José Manuel , Malagón, María M , Pérez-Martínez, Pablo , Laurencikiene, Jurga , Luque, Raul M , Rydén, Mikael , Rangel-Zúñiga, Oriol Alberto , Vendrell, Joan , Guzmán-Ruiz, Rocío , Romero-Cabrera, Juan Luis , Fernández-Veledo, Sonia , Del Río-Moreno, Mercedes , Maymo-Masip, Elsa , Membrives, Antonio , Sánchez-Ceinos, Julia , López-Miranda, José

in Adipocytes / Adipogenesis / Adipose tissue / Body fat / Body mass index / Cell Biology / Cholesterol / Diabetes / Diabetes mellitus (non-insulin dependent) / Endoplasmic reticulum / ER-proteostasis / ERAD / Gene expression / Glucose / High density lipoprotein / Homeostasis / Insulin / Insulin resistance / Lipids / Metabolic disorders / Obesity / obesity-related metabolic diseases / Preadipocytes / Proteins / Proteomics / RNA splicing / Splicing / Transcription factors / Triglycerides / UPR

2021

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Impaired mRNA splicing and proteostasis in preadipocytes in obesity-related metabolic disease

2021

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Impaired mRNA splicing and proteostasis in preadipocytes in obesity-related metabolic disease

2021

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Journal Article

Impaired mRNA splicing and proteostasis in preadipocytes in obesity-related metabolic disease

López-Alcalá, Jaime,

Moreno-Caño, Elena,

Fernández-Real, José Manuel,

Malagón, María M,

Pérez-Martínez, Pablo,

Laurencikiene, Jurga,

Luque, Raul M,

Rydén, Mikael,

Rangel-Zúñiga, Oriol Alberto,

Vendrell, Joan,

Guzmán-Ruiz, Rocío,

Romero-Cabrera, Juan Luis,

Fernández-Veledo, Sonia,

Del Río-Moreno, Mercedes,

Maymo-Masip, Elsa,

Membrives, Antonio,

Sánchez-Ceinos, Julia,

López-Miranda, José

2021

Overview

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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eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd

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