Enhanced Mitochondrial Dynamics and Reactive Oxygen Species Levels with Reduced Antioxidant Defenses in Human Epicardial Adipose Tissue

<b>Background/Objectives</b>: Epicardial adipose tissue (EAT) is metabolically active and is in dynamic crosstalk with the surrounding cardiomyocytes, modulating their function and metabolism. Oxidative stress is a key contributor to cell death and cardiac remodeling, is a hallmark of di...

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Main Authors: Ana Burgeiro, Diana Santos, Ana Catarina R. G. Fonseca, Inês Baldeiras, Ermelindo C. Leal, João Moura, João Costa-Nunes, Patrícia Monteiro Seraphim, Aryane Oliveira, António Canotilho, Gonçalo Coutinho, David Prieto, Pedro Antunes, Manuel Antunes, Eugenia Carvalho
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Language:English
Published: MDPI AG 2025-07-01
Series:Metabolites
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Online Access:https://www.mdpi.com/2218-1989/15/7/481
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author Ana Burgeiro
Diana Santos
Ana Catarina R. G. Fonseca
Inês Baldeiras
Ermelindo C. Leal
João Moura
João Costa-Nunes
Patrícia Monteiro Seraphim
Aryane Oliveira
António Canotilho
Gonçalo Coutinho
David Prieto
Pedro Antunes
Manuel Antunes
Eugenia Carvalho
author_facet Ana Burgeiro
Diana Santos
Ana Catarina R. G. Fonseca
Inês Baldeiras
Ermelindo C. Leal
João Moura
João Costa-Nunes
Patrícia Monteiro Seraphim
Aryane Oliveira
António Canotilho
Gonçalo Coutinho
David Prieto
Pedro Antunes
Manuel Antunes
Eugenia Carvalho
author_sort Ana Burgeiro
collection DOAJ
description <b>Background/Objectives</b>: Epicardial adipose tissue (EAT) is metabolically active and is in dynamic crosstalk with the surrounding cardiomyocytes, modulating their function and metabolism. Oxidative stress is a key contributor to cell death and cardiac remodeling, is a hallmark of diabetes (DM) and cardiovascular disease, such as coronary artery disease (CAD). However, little is known about these processes in EAT from patients undergoing cardiac surgery. This study investigates changes in mitochondrial dynamics, reactive oxygen species (ROS) production, and antioxidant defense levels in EAT compared to subcutaneous adipose tissue (SAT) in patients undergoing cardiac surgery, with a focus on the impact of DM and CAD. <b>Methods</b>: Adipose tissue biopsies were collected from 128 patients undergoing surgical cardiac intervention. Mitochondrial dynamics and oxidative stress markers were analyzed. <b>Results</b>: EAT exhibited increased expression of mitochondrial fusion markers [mitofusin 1 (<i>p</i> ≤ 0.001), mitofusin 2 (<i>p</i> = 0.038), and optic atrophy 1 (<i>p</i> ≤ 0.001)], as well as fission markers [fission 1 <i>(p</i> ≤ 0.001) and dynamin-related protein 1 (<i>p</i> ≤ 0.001)] relative to SAT. Additionally, ROS levels (dihydroethidium, <i>p</i> = 0.004) were elevated, while lipid peroxidation (malondialdehyde, <i>p</i> ≤ 0.001) was reduced in EAT compared to SAT. Reduced glutathione (GSH) levels (<i>p</i> ≤ 0.001) and the redox buffer ratio between reduced and oxidized glutathione (GSH/GSSG, <i>p</i> ≤ 0.001) were significantly increased in EAT. Interestingly, glutathione peroxidase activity (<i>p</i> ≤ 0.001) and the antioxidant defense markers catalase (<i>p</i> ≤ 0.001) and superoxide dismutase 2 (<i>p</i> = 0.001) were significantly reduced in EAT compared to SAT. <b>Conclusions</b>: The findings provide a unique molecular insight into the mitochondrial dynamics and oxidative stress profiles of EAT, highlighting potential avenues for a novel diagnostic method and therapeutic strategies for cardiac disease.
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spelling doaj-art-d1848cbbcfc147dbb50fe07cde8933f72025-08-20T02:47:10ZengMDPI AGMetabolites2218-19892025-07-0115748110.3390/metabo15070481Enhanced Mitochondrial Dynamics and Reactive Oxygen Species Levels with Reduced Antioxidant Defenses in Human Epicardial Adipose TissueAna Burgeiro0Diana Santos1Ana Catarina R. G. Fonseca2Inês Baldeiras3Ermelindo C. Leal4João Moura5João Costa-Nunes6Patrícia Monteiro Seraphim7Aryane Oliveira8António Canotilho9Gonçalo Coutinho10David Prieto11Pedro Antunes12Manuel Antunes13Eugenia Carvalho14CNC—Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, PortugalCNC—Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, PortugalCNC—Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, PortugalCNC—Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, PortugalCNC—Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, PortugalCNC—Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, PortugalCNC—Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, PortugalCNC—Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, PortugalCNC—Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, PortugalCardiothoracic Surgery Unit, University Hospital of Coimbra, 3000-075 Coimbra, PortugalCardiothoracic Surgery Unit, University Hospital of Coimbra, 3000-075 Coimbra, PortugalCardiothoracic Surgery Unit, University Hospital of Coimbra, 3000-075 Coimbra, PortugalCardiothoracic Surgery Unit, University Hospital of Coimbra, 3000-075 Coimbra, PortugalUniversity Clinic for Cardiothoracic Surgery, Faculty of Medicine, University Hospital of Coimbra, 3000-548 Coimbra, PortugalCNC—Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal<b>Background/Objectives</b>: Epicardial adipose tissue (EAT) is metabolically active and is in dynamic crosstalk with the surrounding cardiomyocytes, modulating their function and metabolism. Oxidative stress is a key contributor to cell death and cardiac remodeling, is a hallmark of diabetes (DM) and cardiovascular disease, such as coronary artery disease (CAD). However, little is known about these processes in EAT from patients undergoing cardiac surgery. This study investigates changes in mitochondrial dynamics, reactive oxygen species (ROS) production, and antioxidant defense levels in EAT compared to subcutaneous adipose tissue (SAT) in patients undergoing cardiac surgery, with a focus on the impact of DM and CAD. <b>Methods</b>: Adipose tissue biopsies were collected from 128 patients undergoing surgical cardiac intervention. Mitochondrial dynamics and oxidative stress markers were analyzed. <b>Results</b>: EAT exhibited increased expression of mitochondrial fusion markers [mitofusin 1 (<i>p</i> ≤ 0.001), mitofusin 2 (<i>p</i> = 0.038), and optic atrophy 1 (<i>p</i> ≤ 0.001)], as well as fission markers [fission 1 <i>(p</i> ≤ 0.001) and dynamin-related protein 1 (<i>p</i> ≤ 0.001)] relative to SAT. Additionally, ROS levels (dihydroethidium, <i>p</i> = 0.004) were elevated, while lipid peroxidation (malondialdehyde, <i>p</i> ≤ 0.001) was reduced in EAT compared to SAT. Reduced glutathione (GSH) levels (<i>p</i> ≤ 0.001) and the redox buffer ratio between reduced and oxidized glutathione (GSH/GSSG, <i>p</i> ≤ 0.001) were significantly increased in EAT. Interestingly, glutathione peroxidase activity (<i>p</i> ≤ 0.001) and the antioxidant defense markers catalase (<i>p</i> ≤ 0.001) and superoxide dismutase 2 (<i>p</i> = 0.001) were significantly reduced in EAT compared to SAT. <b>Conclusions</b>: The findings provide a unique molecular insight into the mitochondrial dynamics and oxidative stress profiles of EAT, highlighting potential avenues for a novel diagnostic method and therapeutic strategies for cardiac disease.https://www.mdpi.com/2218-1989/15/7/481epicardial adipose tissuesubcutaneous adipose tissuemitochondrial dynamicsoxidative stressantioxidant defensediabetes mellitus
spellingShingle Ana Burgeiro
Diana Santos
Ana Catarina R. G. Fonseca
Inês Baldeiras
Ermelindo C. Leal
João Moura
João Costa-Nunes
Patrícia Monteiro Seraphim
Aryane Oliveira
António Canotilho
Gonçalo Coutinho
David Prieto
Pedro Antunes
Manuel Antunes
Eugenia Carvalho
Enhanced Mitochondrial Dynamics and Reactive Oxygen Species Levels with Reduced Antioxidant Defenses in Human Epicardial Adipose Tissue
Metabolites
epicardial adipose tissue
subcutaneous adipose tissue
mitochondrial dynamics
oxidative stress
antioxidant defense
diabetes mellitus
title Enhanced Mitochondrial Dynamics and Reactive Oxygen Species Levels with Reduced Antioxidant Defenses in Human Epicardial Adipose Tissue
title_full Enhanced Mitochondrial Dynamics and Reactive Oxygen Species Levels with Reduced Antioxidant Defenses in Human Epicardial Adipose Tissue
title_fullStr Enhanced Mitochondrial Dynamics and Reactive Oxygen Species Levels with Reduced Antioxidant Defenses in Human Epicardial Adipose Tissue
title_full_unstemmed Enhanced Mitochondrial Dynamics and Reactive Oxygen Species Levels with Reduced Antioxidant Defenses in Human Epicardial Adipose Tissue
title_short Enhanced Mitochondrial Dynamics and Reactive Oxygen Species Levels with Reduced Antioxidant Defenses in Human Epicardial Adipose Tissue
title_sort enhanced mitochondrial dynamics and reactive oxygen species levels with reduced antioxidant defenses in human epicardial adipose tissue
topic epicardial adipose tissue
subcutaneous adipose tissue
mitochondrial dynamics
oxidative stress
antioxidant defense
diabetes mellitus
url https://www.mdpi.com/2218-1989/15/7/481
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