Impaired mRNA splicing and proteostasis in preadipocytes in obesity-related metabolic disease
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 diffe...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-09-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/65996 |
| _version_ | 1828375501260980224 |
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| author | Julia Sánchez-Ceinos Rocío Guzmán-Ruiz Oriol Alberto Rangel-Zúñiga Jaime López-Alcalá Elena Moreno-Caño Mercedes Del Río-Moreno Juan Luis Romero-Cabrera Pablo Pérez-Martínez Elsa Maymo-Masip Joan Vendrell Sonia Fernández-Veledo José Manuel Fernández-Real Jurga Laurencikiene Mikael Rydén Antonio Membrives Raul M Luque José López-Miranda María M Malagón |
| author_facet | Julia Sánchez-Ceinos Rocío Guzmán-Ruiz Oriol Alberto Rangel-Zúñiga Jaime López-Alcalá Elena Moreno-Caño Mercedes Del Río-Moreno Juan Luis Romero-Cabrera Pablo Pérez-Martínez Elsa Maymo-Masip Joan Vendrell Sonia Fernández-Veledo José Manuel Fernández-Real Jurga Laurencikiene Mikael Rydén Antonio Membrives Raul M Luque José López-Miranda María M Malagón |
| author_sort | Julia Sánchez-Ceinos |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T07:48:11Z |
| format | Article |
| id | doaj.art-af1e565ee14b40e49f3a99c51d6ad84c |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:48:11Z |
| publishDate | 2021-09-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-af1e565ee14b40e49f3a99c51d6ad84c2022-12-22T02:05:17ZengeLife Sciences Publications LtdeLife2050-084X2021-09-011010.7554/eLife.65996Impaired mRNA splicing and proteostasis in preadipocytes in obesity-related metabolic diseaseJulia Sánchez-Ceinos0https://orcid.org/0000-0002-3131-7057Rocío Guzmán-Ruiz1Oriol Alberto Rangel-Zúñiga2Jaime López-Alcalá3Elena Moreno-Caño4Mercedes Del Río-Moreno5Juan Luis Romero-Cabrera6Pablo Pérez-Martínez7Elsa Maymo-Masip8Joan Vendrell9Sonia Fernández-Veledo10José Manuel Fernández-Real11Jurga Laurencikiene12Mikael Rydén13Antonio Membrives14Raul M Luque15José López-Miranda16María M Malagón17https://orcid.org/0000-0002-2419-2727Department of Cell Biology, Physiology and Immunology, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)/University of Córdoba/Reina Sofía University Hospital, Córdoba, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, SpainDepartment of Cell Biology, Physiology and Immunology, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)/University of Córdoba/Reina Sofía University Hospital, Córdoba, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, SpainCIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain; Lipids and Atherosclerosis Unit, Department of Internal Medicine, IMIBIC, Córdoba, SpainDepartment of Cell Biology, Physiology and Immunology, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)/University of Córdoba/Reina Sofía University Hospital, Córdoba, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, SpainDepartment of Cell Biology, Physiology and Immunology, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)/University of Córdoba/Reina Sofía University Hospital, Córdoba, SpainCIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain; OncObesity and Metabolism Group. Department of Cell Biology, Physiology and Immunology, IMIBIC/University of Córdoba/Reina Sofía University Hospital, Córdoba, SpainLipids and Atherosclerosis Unit, Department of Internal Medicine, IMIBIC, Córdoba, SpainLipids and Atherosclerosis Unit, Department of Internal Medicine, IMIBIC, Córdoba, SpainCIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERdem), Instituto de Salud Carlos III, Madrid, Spain; Hospital Universitari de Tarragona Joan XXIII, Institut d´Investigació Sanitària Pere Virgili Universitat Rovira i Virgil, Tarragona, SpainCIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERdem), Instituto de Salud Carlos III, Madrid, Spain; Hospital Universitari de Tarragona Joan XXIII, Institut d´Investigació Sanitària Pere Virgili Universitat Rovira i Virgil, Tarragona, SpainCIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERdem), Instituto de Salud Carlos III, Madrid, Spain; Hospital Universitari de Tarragona Joan XXIII, Institut d´Investigació Sanitària Pere Virgili Universitat Rovira i Virgil, Tarragona, SpainCIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain; Department of Diabetes, Endocrinology and Nutrition, Dr. Josep Trueta University Hospital, and Eumetabolism and Health Group, Girona Biomedical Research Institute (IdibGi), Girona, SpainLipid Laboratory. Department of Medicine Huddinge/Karolinska Institute (KI)/Karolinska University Hospital, Stockholm, SwedenLipid Laboratory. Department of Medicine Huddinge/Karolinska Institute (KI)/Karolinska University Hospital, Stockholm, SwedenUnidad de Gestión Clínica de Cirugía General y Digestivo, Sección de Obesidad, Reina Sofia University Hospital, Córdoba, SpainCIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain; OncObesity and Metabolism Group. Department of Cell Biology, Physiology and Immunology, IMIBIC/University of Córdoba/Reina Sofía University Hospital, Córdoba, SpainCIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain; Lipids and Atherosclerosis Unit, Department of Internal Medicine, IMIBIC, Córdoba, SpainDepartment of Cell Biology, Physiology and Immunology, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)/University of Córdoba/Reina Sofía University Hospital, Córdoba, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, SpainPreadipocytes 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.https://elifesciences.org/articles/65996preadipocytesobesity-related metabolic diseasesRNA splicingER-proteostasisUPRERAD |
| spellingShingle | Julia Sánchez-Ceinos Rocío Guzmán-Ruiz Oriol Alberto Rangel-Zúñiga Jaime López-Alcalá Elena Moreno-Caño Mercedes Del Río-Moreno Juan Luis Romero-Cabrera Pablo Pérez-Martínez Elsa Maymo-Masip Joan Vendrell Sonia Fernández-Veledo José Manuel Fernández-Real Jurga Laurencikiene Mikael Rydén Antonio Membrives Raul M Luque José López-Miranda María M Malagón Impaired mRNA splicing and proteostasis in preadipocytes in obesity-related metabolic disease eLife preadipocytes obesity-related metabolic diseases RNA splicing ER-proteostasis UPR ERAD |
| title | Impaired mRNA splicing and proteostasis in preadipocytes in obesity-related metabolic disease |
| title_full | Impaired mRNA splicing and proteostasis in preadipocytes in obesity-related metabolic disease |
| title_fullStr | Impaired mRNA splicing and proteostasis in preadipocytes in obesity-related metabolic disease |
| title_full_unstemmed | Impaired mRNA splicing and proteostasis in preadipocytes in obesity-related metabolic disease |
| title_short | Impaired mRNA splicing and proteostasis in preadipocytes in obesity-related metabolic disease |
| title_sort | impaired mrna splicing and proteostasis in preadipocytes in obesity related metabolic disease |
| topic | preadipocytes obesity-related metabolic diseases RNA splicing ER-proteostasis UPR ERAD |
| url | https://elifesciences.org/articles/65996 |
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