The Antagonist Effect of Arachidonic Acid on <i>GLUT4</i> Gene Expression by Nuclear Receptor Type II Regulation
Objectives: Obesity is a complex disease that has a strong association with diet and lifestyle. Dietary factors can influence the expression of key genes connected to insulin resistance, lipid metabolism, and adipose tissue composition. In this study, our objective was to determine gene expression a...
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doaj-03e5daf3ccda4c379a897c21895ab0ac2020-11-25T00:02:55ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-02-0120496310.3390/ijms20040963ijms20040963The Antagonist Effect of Arachidonic Acid on <i>GLUT4</i> Gene Expression by Nuclear Receptor Type II RegulationInmaculada Moreno-Santos0Sara Garcia-Serrano1Hatim Boughanem2Lourdes Garrido-Sanchez3Francisco José Tinahones4Eduardo Garcia-Fuentes5Manuel Macias-Gonzalez6Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, University of Malaga (IBIMA), 29010 Malaga, SpainCIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Unidad de Gestión Clínica de Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario, 29010 Málaga, SpainInstituto de Investigación Biomédica de Málaga (IBIMA), Facultad de Ciencias, Universidad de Málaga, 29010 Málaga, SpainDepartment of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, University of Malaga (IBIMA), 29010 Malaga, SpainDepartment of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, University of Malaga (IBIMA), 29010 Malaga, SpainCIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Unidad de Gestión Clínica de Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario, 29010 Málaga, SpainDepartment of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, University of Malaga (IBIMA), 29010 Malaga, SpainObjectives: Obesity is a complex disease that has a strong association with diet and lifestyle. Dietary factors can influence the expression of key genes connected to insulin resistance, lipid metabolism, and adipose tissue composition. In this study, our objective was to determine gene expression and fatty acid (FA) profiles in visceral adipose tissue (VAT) from lean and morbidly obese individuals. We also aimed to study the agonist effect of dietary factors on glucose metabolism. Design and methods: Lean and low and high insulin resistance morbidly obese subjects (LIR-MO and HIR-MO) were included in this study. The gene expression of liver X receptor type alpha (LXR-α) and glucose transporter type 4 (GLUT4) and the FA profiles in VAT were determined. Additionally, the in vivo and in vitro agonist effects of oleic acid (OA), linoleic acid (LA), and arachidonic acid (AA) by peroxisome proliferator-activated receptor type gamma 2 (PPAR-γ2) on the activity of GLUT4 were studied. Results: Our results showed a dysregulation of GLUT4 and LXR-α in VAT of morbidly obese subjects. In addition, a specific FA profile for morbidly obese individuals was found. Finally, AA was an PPAR-γ2 agonist that activates the expression of GLUT4. Conclusions: Our study suggests a dysregulation of LXR-α and GLUT4 expression in VAT of morbidly obese individuals. FA profiles in VAT could elucidate their possible role in lipolysis and adipogenesis. Finally, AA binds to PPAR-γ2 to activate the expression of GLUT4 in the HepG2 cell line, showing an alternative insulin-independent activation of GLUT4.https://www.mdpi.com/1422-0067/20/4/963obesityinsulin resistanceLXR-αGLUT4fatty acidsPPAR-γ2arachidonic acid |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Inmaculada Moreno-Santos Sara Garcia-Serrano Hatim Boughanem Lourdes Garrido-Sanchez Francisco José Tinahones Eduardo Garcia-Fuentes Manuel Macias-Gonzalez |
spellingShingle |
Inmaculada Moreno-Santos Sara Garcia-Serrano Hatim Boughanem Lourdes Garrido-Sanchez Francisco José Tinahones Eduardo Garcia-Fuentes Manuel Macias-Gonzalez The Antagonist Effect of Arachidonic Acid on <i>GLUT4</i> Gene Expression by Nuclear Receptor Type II Regulation International Journal of Molecular Sciences obesity insulin resistance LXR-α GLUT4 fatty acids PPAR-γ2 arachidonic acid |
author_facet |
Inmaculada Moreno-Santos Sara Garcia-Serrano Hatim Boughanem Lourdes Garrido-Sanchez Francisco José Tinahones Eduardo Garcia-Fuentes Manuel Macias-Gonzalez |
author_sort |
Inmaculada Moreno-Santos |
title |
The Antagonist Effect of Arachidonic Acid on <i>GLUT4</i> Gene Expression by Nuclear Receptor Type II Regulation |
title_short |
The Antagonist Effect of Arachidonic Acid on <i>GLUT4</i> Gene Expression by Nuclear Receptor Type II Regulation |
title_full |
The Antagonist Effect of Arachidonic Acid on <i>GLUT4</i> Gene Expression by Nuclear Receptor Type II Regulation |
title_fullStr |
The Antagonist Effect of Arachidonic Acid on <i>GLUT4</i> Gene Expression by Nuclear Receptor Type II Regulation |
title_full_unstemmed |
The Antagonist Effect of Arachidonic Acid on <i>GLUT4</i> Gene Expression by Nuclear Receptor Type II Regulation |
title_sort |
antagonist effect of arachidonic acid on <i>glut4</i> gene expression by nuclear receptor type ii regulation |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2019-02-01 |
description |
Objectives: Obesity is a complex disease that has a strong association with diet and lifestyle. Dietary factors can influence the expression of key genes connected to insulin resistance, lipid metabolism, and adipose tissue composition. In this study, our objective was to determine gene expression and fatty acid (FA) profiles in visceral adipose tissue (VAT) from lean and morbidly obese individuals. We also aimed to study the agonist effect of dietary factors on glucose metabolism. Design and methods: Lean and low and high insulin resistance morbidly obese subjects (LIR-MO and HIR-MO) were included in this study. The gene expression of liver X receptor type alpha (LXR-α) and glucose transporter type 4 (GLUT4) and the FA profiles in VAT were determined. Additionally, the in vivo and in vitro agonist effects of oleic acid (OA), linoleic acid (LA), and arachidonic acid (AA) by peroxisome proliferator-activated receptor type gamma 2 (PPAR-γ2) on the activity of GLUT4 were studied. Results: Our results showed a dysregulation of GLUT4 and LXR-α in VAT of morbidly obese subjects. In addition, a specific FA profile for morbidly obese individuals was found. Finally, AA was an PPAR-γ2 agonist that activates the expression of GLUT4. Conclusions: Our study suggests a dysregulation of LXR-α and GLUT4 expression in VAT of morbidly obese individuals. FA profiles in VAT could elucidate their possible role in lipolysis and adipogenesis. Finally, AA binds to PPAR-γ2 to activate the expression of GLUT4 in the HepG2 cell line, showing an alternative insulin-independent activation of GLUT4. |
topic |
obesity insulin resistance LXR-α GLUT4 fatty acids PPAR-γ2 arachidonic acid |
url |
https://www.mdpi.com/1422-0067/20/4/963 |
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