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ATP-binding cassette transporter A1 (ABCA1) expression in adipose tissue and its modulation with insulin resistance in obesity

PURPOSE: Adipose tissue dysfunction is at the center of metabolic dysfunctions associated with obesity. Through studies in isolated adipocytes and mouse models, ATP-binding cassette transporter A1 (ABCA1) expression in the adipose tissue has been shown to regulate high-density lipoprotein (HDL) chol...

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Autores principales: Vincent, Vinnyfred, Thakkar, Himani, Aggarwal, Sandeep, Mridha, Asit Ranjan, Ramakrishnan, Lakshmy, Singh, Archna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6395069/
https://www.ncbi.nlm.nih.gov/pubmed/30881070
http://dx.doi.org/10.2147/DMSO.S186565
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author Vincent, Vinnyfred
Thakkar, Himani
Aggarwal, Sandeep
Mridha, Asit Ranjan
Ramakrishnan, Lakshmy
Singh, Archna
author_facet Vincent, Vinnyfred
Thakkar, Himani
Aggarwal, Sandeep
Mridha, Asit Ranjan
Ramakrishnan, Lakshmy
Singh, Archna
author_sort Vincent, Vinnyfred
collection PubMed
description PURPOSE: Adipose tissue dysfunction is at the center of metabolic dysfunctions associated with obesity. Through studies in isolated adipocytes and mouse models, ATP-binding cassette transporter A1 (ABCA1) expression in the adipose tissue has been shown to regulate high-density lipoprotein (HDL) cholesterol levels in the circulation and insulin sensitivity at both adipose tissue and whole-body levels. We aimed to explore the possible link between ABCA1 expression in the adipose tissue and metabolic derangements associated with obesity in humans. PATIENTS AND METHODS: This exploratory study among individuals who were lean (body mass index [BMI]: 22.3±0.34 kg/m(2), n=28) and obese (BMI: 44.48±5.3 kg/m(2), n=34) compared the expression of ABCA1, adiponectin and GLUT4 (SLC2A4) in visceral and subcutaneous adipose tissue using quantitative real-time PCR and immunohistochemistry. Homeostatic model assessment for insulin resistance (HOMA-IR) and adipose tissue insulin resistance (adipo-IR) were used as insulin resistance markers. RESULTS: Visceral adipose tissue from individuals who were obese had significantly lower ABCA1 (P=0.04 for mRNA and protein) and adiponectin (P=0.001 for mRNA) expression compared to that from lean individuals. Subcutaneous adipose tissue did not show any significant difference in the expression. When individuals were divided into insulin-sensitive (IS) and insulin-resistant (IR) groups based on HOMA-IR, IR individuals had lower ABCA1 (P=0.0001 for mRNA and P=0.009 for protein) expression compared to IS individuals in visceral adipose tissue, but not in subcutaneous adipose tissue. The difference was significant after adjusting for age, gender and BMI. ABCA1 mRNA expression in visceral adipose tissue correlated negatively with both HOMA-IR (r=−0.44, P=0.0003) and adipo-IR (r=−0.35, P=0.005) after adjusting for age, gender and BMI. ABCA1 expression in either visceral or subcutaneous adipose tissue did not have any significant correlation with HDL cholesterol levels or mean adipocyte area. CONCLUSION: Obesity and insulin resistance are associated with lower expression of ABCA1 in visceral adipose tissue in humans.
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spelling pubmed-63950692019-03-15 ATP-binding cassette transporter A1 (ABCA1) expression in adipose tissue and its modulation with insulin resistance in obesity Vincent, Vinnyfred Thakkar, Himani Aggarwal, Sandeep Mridha, Asit Ranjan Ramakrishnan, Lakshmy Singh, Archna Diabetes Metab Syndr Obes Original Research PURPOSE: Adipose tissue dysfunction is at the center of metabolic dysfunctions associated with obesity. Through studies in isolated adipocytes and mouse models, ATP-binding cassette transporter A1 (ABCA1) expression in the adipose tissue has been shown to regulate high-density lipoprotein (HDL) cholesterol levels in the circulation and insulin sensitivity at both adipose tissue and whole-body levels. We aimed to explore the possible link between ABCA1 expression in the adipose tissue and metabolic derangements associated with obesity in humans. PATIENTS AND METHODS: This exploratory study among individuals who were lean (body mass index [BMI]: 22.3±0.34 kg/m(2), n=28) and obese (BMI: 44.48±5.3 kg/m(2), n=34) compared the expression of ABCA1, adiponectin and GLUT4 (SLC2A4) in visceral and subcutaneous adipose tissue using quantitative real-time PCR and immunohistochemistry. Homeostatic model assessment for insulin resistance (HOMA-IR) and adipose tissue insulin resistance (adipo-IR) were used as insulin resistance markers. RESULTS: Visceral adipose tissue from individuals who were obese had significantly lower ABCA1 (P=0.04 for mRNA and protein) and adiponectin (P=0.001 for mRNA) expression compared to that from lean individuals. Subcutaneous adipose tissue did not show any significant difference in the expression. When individuals were divided into insulin-sensitive (IS) and insulin-resistant (IR) groups based on HOMA-IR, IR individuals had lower ABCA1 (P=0.0001 for mRNA and P=0.009 for protein) expression compared to IS individuals in visceral adipose tissue, but not in subcutaneous adipose tissue. The difference was significant after adjusting for age, gender and BMI. ABCA1 mRNA expression in visceral adipose tissue correlated negatively with both HOMA-IR (r=−0.44, P=0.0003) and adipo-IR (r=−0.35, P=0.005) after adjusting for age, gender and BMI. ABCA1 expression in either visceral or subcutaneous adipose tissue did not have any significant correlation with HDL cholesterol levels or mean adipocyte area. CONCLUSION: Obesity and insulin resistance are associated with lower expression of ABCA1 in visceral adipose tissue in humans. Dove Medical Press 2019-02-25 /pmc/articles/PMC6395069/ /pubmed/30881070 http://dx.doi.org/10.2147/DMSO.S186565 Text en © 2019 Vincent et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Vincent, Vinnyfred
Thakkar, Himani
Aggarwal, Sandeep
Mridha, Asit Ranjan
Ramakrishnan, Lakshmy
Singh, Archna
ATP-binding cassette transporter A1 (ABCA1) expression in adipose tissue and its modulation with insulin resistance in obesity
title ATP-binding cassette transporter A1 (ABCA1) expression in adipose tissue and its modulation with insulin resistance in obesity
title_full ATP-binding cassette transporter A1 (ABCA1) expression in adipose tissue and its modulation with insulin resistance in obesity
title_fullStr ATP-binding cassette transporter A1 (ABCA1) expression in adipose tissue and its modulation with insulin resistance in obesity
title_full_unstemmed ATP-binding cassette transporter A1 (ABCA1) expression in adipose tissue and its modulation with insulin resistance in obesity
title_short ATP-binding cassette transporter A1 (ABCA1) expression in adipose tissue and its modulation with insulin resistance in obesity
title_sort atp-binding cassette transporter a1 (abca1) expression in adipose tissue and its modulation with insulin resistance in obesity
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6395069/
https://www.ncbi.nlm.nih.gov/pubmed/30881070
http://dx.doi.org/10.2147/DMSO.S186565
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