PMID- 34545810
OWN - NLM
STAT- MEDLINE
DCOM- 20211130
LR  - 20211207
IS  - 2050-084X (Electronic)
IS  - 2050-084X (Linking)
VI  - 10
DP  - 2021 Sep 21
TI  - Impaired mRNA splicing and proteostasis in preadipocytes in obesity-related 
      metabolic disease.
LID - 10.7554/eLife.65996 [doi]
LID - e65996
AB  - 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.
CI  - (c) 2021, Sanchez-Ceinos et al.
FAU - Sanchez-Ceinos, Julia
AU  - Sanchez-Ceinos J
AUID- ORCID: 0000-0002-3131-7057
AD  - Department of Cell Biology, Physiology and Immunology, Instituto Maimonides de 
      Investigacion Biomedica de Cordoba (IMIBIC)/University of Cordoba/Reina Sofia 
      University Hospital, Cordoba, Spain.
AD  - CIBER Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Instituto de Salud 
      Carlos III, Madrid, Spain.
FAU - Guzman-Ruiz, Rocio
AU  - Guzman-Ruiz R
AD  - Department of Cell Biology, Physiology and Immunology, Instituto Maimonides de 
      Investigacion Biomedica de Cordoba (IMIBIC)/University of Cordoba/Reina Sofia 
      University Hospital, Cordoba, Spain.
AD  - CIBER Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Instituto de Salud 
      Carlos III, Madrid, Spain.
FAU - Rangel-Zuniga, Oriol Alberto
AU  - Rangel-Zuniga OA
AD  - CIBER Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Instituto de Salud 
      Carlos III, Madrid, Spain.
AD  - Lipids and Atherosclerosis Unit, Department of Internal Medicine, IMIBIC, 
      Cordoba, Spain.
FAU - Lopez-Alcala, Jaime
AU  - Lopez-Alcala J
AD  - Department of Cell Biology, Physiology and Immunology, Instituto Maimonides de 
      Investigacion Biomedica de Cordoba (IMIBIC)/University of Cordoba/Reina Sofia 
      University Hospital, Cordoba, Spain.
AD  - CIBER Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Instituto de Salud 
      Carlos III, Madrid, Spain.
FAU - Moreno-Cano, Elena
AU  - Moreno-Cano E
AD  - Department of Cell Biology, Physiology and Immunology, Instituto Maimonides de 
      Investigacion Biomedica de Cordoba (IMIBIC)/University of Cordoba/Reina Sofia 
      University Hospital, Cordoba, Spain.
FAU - Del Rio-Moreno, Mercedes
AU  - Del Rio-Moreno M
AD  - CIBER Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Instituto de Salud 
      Carlos III, Madrid, Spain.
AD  - OncObesity and Metabolism Group. Department of Cell Biology, Physiology and 
      Immunology, IMIBIC/University of Cordoba/Reina Sofia University Hospital, 
      Cordoba, Spain.
FAU - Romero-Cabrera, Juan Luis
AU  - Romero-Cabrera JL
AD  - Lipids and Atherosclerosis Unit, Department of Internal Medicine, IMIBIC, 
      Cordoba, Spain.
FAU - Perez-Martinez, Pablo
AU  - Perez-Martinez P
AD  - Lipids and Atherosclerosis Unit, Department of Internal Medicine, IMIBIC, 
      Cordoba, Spain.
FAU - Maymo-Masip, Elsa
AU  - Maymo-Masip E
AD  - CIBER de Diabetes y Enfermedades Metabolicas Asociadas (CIBERdem), Instituto de 
      Salud Carlos III, Madrid, Spain.
AD  - Hospital Universitari de Tarragona Joan XXIII, Institut d Investigacio Sanitaria 
      Pere Virgili Universitat Rovira i Virgil, Tarragona, Spain.
FAU - Vendrell, Joan
AU  - Vendrell J
AD  - CIBER de Diabetes y Enfermedades Metabolicas Asociadas (CIBERdem), Instituto de 
      Salud Carlos III, Madrid, Spain.
AD  - Hospital Universitari de Tarragona Joan XXIII, Institut d Investigacio Sanitaria 
      Pere Virgili Universitat Rovira i Virgil, Tarragona, Spain.
FAU - Fernandez-Veledo, Sonia
AU  - Fernandez-Veledo S
AD  - CIBER de Diabetes y Enfermedades Metabolicas Asociadas (CIBERdem), Instituto de 
      Salud Carlos III, Madrid, Spain.
AD  - Hospital Universitari de Tarragona Joan XXIII, Institut d Investigacio Sanitaria 
      Pere Virgili Universitat Rovira i Virgil, Tarragona, Spain.
FAU - Fernandez-Real, Jose Manuel
AU  - Fernandez-Real JM
AD  - CIBER Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Instituto de Salud 
      Carlos III, Madrid, Spain.
AD  - Department of Diabetes, Endocrinology and Nutrition, Dr. Josep Trueta University 
      Hospital, and Eumetabolism and Health Group, Girona Biomedical Research Institute 
      (IdibGi), Girona, Spain.
FAU - Laurencikiene, Jurga
AU  - Laurencikiene J
AD  - Lipid Laboratory. Department of Medicine Huddinge/Karolinska Institute 
      (KI)/Karolinska University Hospital, Stockholm, Sweden.
FAU - Ryden, Mikael
AU  - Ryden M
AD  - Lipid Laboratory. Department of Medicine Huddinge/Karolinska Institute 
      (KI)/Karolinska University Hospital, Stockholm, Sweden.
FAU - Membrives, Antonio
AU  - Membrives A
AD  - Unidad de Gestion Clinica de Cirugia General y Digestivo, Seccion de Obesidad, 
      Reina Sofia University Hospital, Cordoba, Spain.
FAU - Luque, Raul M
AU  - Luque RM
AD  - CIBER Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Instituto de Salud 
      Carlos III, Madrid, Spain.
AD  - OncObesity and Metabolism Group. Department of Cell Biology, Physiology and 
      Immunology, IMIBIC/University of Cordoba/Reina Sofia University Hospital, 
      Cordoba, Spain.
FAU - Lopez-Miranda, Jose
AU  - Lopez-Miranda J
AD  - CIBER Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Instituto de Salud 
      Carlos III, Madrid, Spain.
AD  - Lipids and Atherosclerosis Unit, Department of Internal Medicine, IMIBIC, 
      Cordoba, Spain.
FAU - Malagon, Maria M
AU  - Malagon MM
AUID- ORCID: 0000-0002-2419-2727
AD  - Department of Cell Biology, Physiology and Immunology, Instituto Maimonides de 
      Investigacion Biomedica de Cordoba (IMIBIC)/University of Cordoba/Reina Sofia 
      University Hospital, Cordoba, Spain.
AD  - CIBER Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Instituto de Salud 
      Carlos III, Madrid, Spain.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210921
PL  - England
TA  - Elife
JT  - eLife
JID - 101579614
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Adipocytes/cytology/metabolism/*physiology
MH  - Adipogenesis
MH  - Adult
MH  - Cell Differentiation
MH  - Cell Line
MH  - Diabetes Mellitus, Type 2/*complications/genetics/metabolism
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Obesity/*complications/genetics/metabolism
MH  - *Proteostasis
MH  - RNA, Messenger/*genetics
PMC - PMC8545398
OTO - NOTNLM
OT  - ER-proteostasis
OT  - ERAD
OT  - RNA splicing
OT  - UPR
OT  - cell biology
OT  - human
OT  - obesity-related metabolic diseases
OT  - preadipocytes
COIS- JS, RG, OR, JL, EM, MD, JR, PP, EM, JV, SF, JF, JL, MR, AM, RL, JL, MM No 
      competing interests declared
EDAT- 2021/09/22 06:00
MHDA- 2021/12/01 06:00
PMCR- 2021/09/21
CRDT- 2021/09/21 08:40
PHST- 2020/12/21 00:00 [received]
PHST- 2021/09/20 00:00 [accepted]
PHST- 2021/09/22 06:00 [pubmed]
PHST- 2021/12/01 06:00 [medline]
PHST- 2021/09/21 08:40 [entrez]
PHST- 2021/09/21 00:00 [pmc-release]
AID - 65996 [pii]
AID - 10.7554/eLife.65996 [doi]
PST - epublish
SO  - Elife. 2021 Sep 21;10:e65996. doi: 10.7554/eLife.65996.