Impaired mRNA splicing and proteostasis in preadipocytes in obesity-related metabolic disease
| Autor: | Antonio Membrives, Elsa Maymó-Masip, Jurga Laurencikiene, Elena Moreno-Caño, Oriol A. Rangel-Zuñiga, Mikael Rydén, Joan Vendrell, José Manuel Fernández-Real, Rocío Guzmán-Ruiz, Julia Sánchez-Ceinos, Sonia Fernández-Veledo, Juan Luis Romero-Cabrera, Raúl M. Luque, María M. Malagón, Jose Lopez-Miranda, Jaime López-Alcalá, Pablo Perez-Martinez, Mercedes del Rio-Moreno |
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| Přispěvatelé: | [Sánchez-Ceinos,J, Guzmán-Ruiz,R, López-Alcalá,J, Moreno-Caño,E, Malagón,MM] Department of Cell Biology, Physiology and Immunology, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)/University of Córdoba/Reina Sofía University Hospital, Córdoba, Spain. [Sánchez-Ceinos,J, Rangel-Zúñiga,OA, Del Río-Moreno,M, Fernández-Real,JM, Luque,RM, López-Miranda,J, Malagón,MM] CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain. [Rangel-Zúñiga,OA, Romero-Cabrera,JL, Pérez-Martínez,P, López-Miranda,J] Lipids and Atherosclerosis Unit, Department of Internal Medicine, IMIBIC, Córdoba, Spain. [Del Río-Moreno,M, Luque,RM] OncObesity and Metabolism Group. Department of Cell Biology, Physiology and Immunology, IMIBIC/University of Córdoba/Reina Sofía University Hospital, Córdoba, Spain. [Maymo-Masip,E, Vendrell,J, Fernández-Veledo,S] CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERdem), Instituto de Salud Carlos III, Madrid, Spain. [Maymo-Masip,E, Fernández-Veledo,S] Hospital Universitari de Tarragona Joan XXIII, Institut d´Investigació Sanitària Pere Virgili Universitat Rovira i Virgil, Tarragona, Spain. [Fernández-Real,JM] Department of Diabetes, Endocrinology and Nutrition, Dr. Josep Trueta University Hospital, and Eumetabolism and Health Group, Girona Biomedical Research Institute (IdibGi), Girona, Spain. [Laurencikiene,J, Rydén,M] Lipid Laboratory. Department of Medicine Huddinge/Karolinska Institute (KI)/Karolinska University Hospital, Stockholm, Sweden. [Membrives,A] Unidad de Gestión Clínica de Cirugía General y Digestivo, Sección de Obesidad, Reina Sofia University Hospital, Córdoba, Spain., Ministerio de Ciencia, Innovación y Universidades/FEDER (BFU2013-44229‐R, BFU2016‐76711‐R, BFU2017‐90578‐REDT to MMM, RTI2018-093919-B-I00 to SF-V), Consejería de Salud y Bienestar Social/Junta de Andalucía/FEDER (PI‐0200/2013 to MMM, PI‐0159‐2016 to RG‐R), Instituto de Salud Carlos III (ISCIII)/FEDER (PIE14/00005 to JL‐M and MMM, PI16/00264 to RML, PI17/0153 to JV), Fondo de Investigación Sanitaria/ISCIII/FEDER Miguel Servet tenure-track program (CP10 /00438, CPII16/00008 to SF-V), Research Plan of University of Córdoba (Mod 2.5, 2019 to RG-R), Co-funded by European Regional Development Fund/European Social Fund 'Investing in your future', and Consejería de Economía, Conocimiento, Empresas y universidad/Junta de Andalucía/FEDER (BIO-0139). CIBEROBN is an initiative of the ISCIII, Spain. |
| Rok vydání: | 2021 |
| Předmět: |
Male
Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Differentiation [Medical Subject Headings] Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Proteostasis Deficiencies [Medical Subject Headings] obesity-related metabolic diseases RNA splicing Expansión de tejido Obesidad Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Differentiation::Adipogenesis [Medical Subject Headings] Metabolic disease Adipose tissue UPR ER-proteostasis Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] chemistry.chemical_compound Anatomy::Cells::Cells Cultured::Cell Line [Medical Subject Headings] Adipocyte Adipocytes Biology (General) Adipogenesis General Neuroscience Cell Differentiation General Medicine Middle Aged Analytical Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures Operative::Reconstructive Surgical Procedures::Tissue Expansion [Medical Subject Headings] Enfermedades metabólicas Anatomy::Cells::Connective Tissue Cells::Adipocytes [Medical Subject Headings] Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Diabetes Mellitus::Diabetes Mellitus Type 2 [Medical Subject Headings] Medicine Female Research Article Human Adult preadipocytes medicine.medical_specialty Spliceosome QH301-705.5 mRNA Science Biology Protein degradation General Biochemistry Genetics and Molecular Biology Cell Line Insulin resistance Internal medicine Adipocitos medicine Humans RNA Messenger Obesity Persons::Persons::Age Groups::Adult [Medical Subject Headings] General Immunology and Microbiology ARN mensajero Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings] Cell Biology Chemicals and Drugs::Nucleic Acids Nucleotides and Nucleosides::Nucleic Acids::RNA::RNA Messenger [Medical Subject Headings] Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases [Medical Subject Headings] ERAD medicine.disease Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::Obesity [Medical Subject Headings] Proteostasis Endocrinology Diabetes Mellitus Type 2 chemistry Tissue expansion |
| Zdroj: | eLife, Vol 10 (2021) eLife |
| ISSN: | 2050-084X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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