eLife | |
Impaired mRNA splicing and proteostasis in preadipocytes in obesity-related metabolic disease | |
Jaime López-Alcalá1  Pablo Pérez-Martínez1  Rocío Guzmán-Ruiz1  Antonio Membrives2  José López-Miranda2  Mercedes Del Río-Moreno3  Sonia Fernández-Veledo4  Elena Moreno-Caño5  Joan Vendrell5  Raul M Luque6  Mikael Rydén6  María M Malagón6  Juan Luis Romero-Cabrera7  Elsa Maymo-Masip7  Oriol Alberto Rangel-Zúñiga7  Julia Sánchez-Ceinos7  Jurga Laurencikiene8  José Manuel Fernández-Real8  | |
[1] CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain;Hospital Universitari de Tarragona Joan XXIII, Institut d´Investigació Sanitària Pere Virgili Universitat Rovira i Virgil, Tarragona, Spain;Lipids and Atherosclerosis Unit, Department of Internal Medicine, IMIBIC, Córdoba, Spain;OncObesity and Metabolism Group. Department of Cell Biology, Physiology and Immunology, IMIBIC/University of Córdoba/Reina Sofía University Hospital, Córdoba, Spain;CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain;CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERdem), Instituto de Salud Carlos III, Madrid, Spain;Department of Cell Biology, Physiology and Immunology, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)/University of Córdoba/Reina Sofía University Hospital, Córdoba, Spain;Lipids and Atherosclerosis Unit, Department of Internal Medicine, IMIBIC, Córdoba, Spain; | |
关键词: preadipocytes; obesity-related metabolic diseases; RNA splicing; ER-proteostasis; UPR; ERAD; | |
DOI : 10.7554/eLife.65996 | |
来源: DOAJ |
【 摘 要 】
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.
【 授权许可】
Unknown