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CABLES1 expression is reduced in human subcutaneous adipose tissue in obesity and type 2 diabetes but may not directly impact adipocyte glucose and lipid metabolism

Cdk5 and Abl enzyme substrate 1 (CABLES1) is a cell cycle regulator that has previously been identified as a candidate gene for obesity-related phenotypes, but little is known about its role in adipose tissue metabolism. In this study, we explore the role of CABLES1 in obesity and type 2 diabetes (T...

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Autores principales: Hetty, Susanne, Vranic, Milica, Kamble, Prasad G, Lundqvist, Martin H, Pereira, Maria J, Eriksson, Jan W
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10413912/
https://www.ncbi.nlm.nih.gov/pubmed/37555665
http://dx.doi.org/10.1080/21623945.2023.2242997
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author Hetty, Susanne
Vranic, Milica
Kamble, Prasad G
Lundqvist, Martin H
Pereira, Maria J
Eriksson, Jan W
author_facet Hetty, Susanne
Vranic, Milica
Kamble, Prasad G
Lundqvist, Martin H
Pereira, Maria J
Eriksson, Jan W
author_sort Hetty, Susanne
collection PubMed
description Cdk5 and Abl enzyme substrate 1 (CABLES1) is a cell cycle regulator that has previously been identified as a candidate gene for obesity-related phenotypes, but little is known about its role in adipose tissue metabolism. In this study, we explore the role of CABLES1 in obesity and type 2 diabetes (T2D) in human subcutaneous adipose tissue (SAT). We performed gene expression analysis of SAT obtained from subjects with and without T2D, and from a second validation cohort consisting of subjects without T2D. We used CRISPR/Cas9 genome editing to perform CABLES1 loss-of-function studies in human primary preadipocytes and assessed them functionally after differentiation. CABLES1 gene expression in SAT was decreased in T2D by almost 25%, and inversely associated with insulin resistance markers and hyperglycaemia. mRNA levels were reduced with increasing BMI and negatively correlated with obesity markers. We found that adipocytes are likely the main CABLES1-expressing cell type in SAT, but CABLES1 depletion in adipocytes caused no phenotypical changes in regards to differentiation, glucose uptake, or expression of key genes of adipocyte function. These findings suggest that CABLES1 gene expression in SAT might be altered in obesity and T2D as a consequence of metabolic dysregulation rather than being a causal factor.
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spelling pubmed-104139122023-08-11 CABLES1 expression is reduced in human subcutaneous adipose tissue in obesity and type 2 diabetes but may not directly impact adipocyte glucose and lipid metabolism Hetty, Susanne Vranic, Milica Kamble, Prasad G Lundqvist, Martin H Pereira, Maria J Eriksson, Jan W Adipocyte Research Paper Cdk5 and Abl enzyme substrate 1 (CABLES1) is a cell cycle regulator that has previously been identified as a candidate gene for obesity-related phenotypes, but little is known about its role in adipose tissue metabolism. In this study, we explore the role of CABLES1 in obesity and type 2 diabetes (T2D) in human subcutaneous adipose tissue (SAT). We performed gene expression analysis of SAT obtained from subjects with and without T2D, and from a second validation cohort consisting of subjects without T2D. We used CRISPR/Cas9 genome editing to perform CABLES1 loss-of-function studies in human primary preadipocytes and assessed them functionally after differentiation. CABLES1 gene expression in SAT was decreased in T2D by almost 25%, and inversely associated with insulin resistance markers and hyperglycaemia. mRNA levels were reduced with increasing BMI and negatively correlated with obesity markers. We found that adipocytes are likely the main CABLES1-expressing cell type in SAT, but CABLES1 depletion in adipocytes caused no phenotypical changes in regards to differentiation, glucose uptake, or expression of key genes of adipocyte function. These findings suggest that CABLES1 gene expression in SAT might be altered in obesity and T2D as a consequence of metabolic dysregulation rather than being a causal factor. Taylor & Francis 2023-08-09 /pmc/articles/PMC10413912/ /pubmed/37555665 http://dx.doi.org/10.1080/21623945.2023.2242997 Text en © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.
spellingShingle Research Paper
Hetty, Susanne
Vranic, Milica
Kamble, Prasad G
Lundqvist, Martin H
Pereira, Maria J
Eriksson, Jan W
CABLES1 expression is reduced in human subcutaneous adipose tissue in obesity and type 2 diabetes but may not directly impact adipocyte glucose and lipid metabolism
title CABLES1 expression is reduced in human subcutaneous adipose tissue in obesity and type 2 diabetes but may not directly impact adipocyte glucose and lipid metabolism
title_full CABLES1 expression is reduced in human subcutaneous adipose tissue in obesity and type 2 diabetes but may not directly impact adipocyte glucose and lipid metabolism
title_fullStr CABLES1 expression is reduced in human subcutaneous adipose tissue in obesity and type 2 diabetes but may not directly impact adipocyte glucose and lipid metabolism
title_full_unstemmed CABLES1 expression is reduced in human subcutaneous adipose tissue in obesity and type 2 diabetes but may not directly impact adipocyte glucose and lipid metabolism
title_short CABLES1 expression is reduced in human subcutaneous adipose tissue in obesity and type 2 diabetes but may not directly impact adipocyte glucose and lipid metabolism
title_sort cables1 expression is reduced in human subcutaneous adipose tissue in obesity and type 2 diabetes but may not directly impact adipocyte glucose and lipid metabolism
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10413912/
https://www.ncbi.nlm.nih.gov/pubmed/37555665
http://dx.doi.org/10.1080/21623945.2023.2242997
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