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...
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eLife Sciences Publications Ltd
2021
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oai:doaj.org-article:af1e565ee14b40e49f3a99c51d6ad84c2021-12-03T16:01:56ZImpaired mRNA splicing and proteostasis in preadipocytes in obesity-related metabolic disease10.7554/eLife.659962050-084Xe65996https://doaj.org/article/af1e565ee14b40e49f3a99c51d6ad84c2021-09-01T00:00:00Zhttps://elifesciences.org/articles/65996https://doaj.org/toc/2050-084XPreadipocytes 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.Julia Sánchez-CeinosRocío Guzmán-RuizOriol Alberto Rangel-ZúñigaJaime López-AlcaláElena Moreno-CañoMercedes Del Río-MorenoJuan Luis Romero-CabreraPablo Pérez-MartínezElsa Maymo-MasipJoan VendrellSonia Fernández-VeledoJosé Manuel Fernández-RealJurga LaurencikieneMikael RydénAntonio MembrivesRaul M LuqueJosé López-MirandaMaría M MalagóneLife Sciences Publications Ltdarticlepreadipocytesobesity-related metabolic diseasesRNA splicingER-proteostasisUPRERADMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
preadipocytes obesity-related metabolic diseases RNA splicing ER-proteostasis UPR ERAD Medicine R Science Q Biology (General) QH301-705.5 |
| spellingShingle |
preadipocytes obesity-related metabolic diseases RNA splicing ER-proteostasis UPR ERAD Medicine R Science Q Biology (General) QH301-705.5 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 |
| 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. |
| format |
article |
| 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 |
| title |
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_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_sort |
impaired mrna splicing and proteostasis in preadipocytes in obesity-related metabolic disease |
| publisher |
eLife Sciences Publications Ltd |
| publishDate |
2021 |
| url |
https://doaj.org/article/af1e565ee14b40e49f3a99c51d6ad84c |
| work_keys_str_mv |
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