Apolipoprotein J protects cardiomyocytes from lipid-mediated inflammation and cytotoxicity induced by the epicardial adipose tissue of diabetic patients

Diabetic patients present increased volume and functional alterations in epicardial adipose tissue (EAT). We aimed to analyze EAT from type 2 diabetic patients and the inflammatory and cytotoxic effects induced on cardiomyocytes. Furthermore, we analyzed the cardioprotective role of apolipoprotein J...

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Authors: Puig Grifol, Núria|||0000-0002-4699-3162; Rives Jimenez, Jose|||0009-0001-5725-9270; Gil-Millan, Pedro; Miñambres, Inka|||0000-0002-0899-3938; Ginel, Antonino|||0000-0002-8820-7545; Tauron, Manel|||0000-0002-5864-519X; Bonaterra-Pastra, Anna|||0000-0002-1480-622X; Hernandez Guillamon, Maria Mar|||0000-0001-8844-0091; Pérez, Antonio|||0000-0001-5528-1143; Sánchez Quesada, José Luis|||0000-0003-0224-591X; Benitez, Sonia|||0000-0003-3565-0743
Format: Article
Publication date:2024
Country:España
Institution:Universitat Autònoma de Barcelona
Repository:Dipòsit Digital de Documents de la UAB
Language:English
OAI Identifier:oai:ddd.uab.cat:306970
Online Access:https://ddd.uab.cat/record/306970
https://dx.doi.org/urn:doi:10.1016/j.biopha.2024.116779
Access Level:Open access
Keyword:Apolipoprotein J
Apoptosis
Ceramides
Coronary artery disease
Epicardial adipose tissue
Fatty acids
Inflammation
Type 2 diabetes
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author Puig Grifol, Núria|||0000-0002-4699-3162
author2 Rives Jimenez, Jose|||0009-0001-5725-9270
Gil-Millan, Pedro
Miñambres, Inka|||0000-0002-0899-3938
Ginel, Antonino|||0000-0002-8820-7545
Tauron, Manel|||0000-0002-5864-519X
Bonaterra-Pastra, Anna|||0000-0002-1480-622X
Hernandez Guillamon, Maria Mar|||0000-0001-8844-0091
Pérez, Antonio|||0000-0001-5528-1143
Sánchez Quesada, José Luis|||0000-0003-0224-591X
Benitez, Sonia|||0000-0003-3565-0743
author2_role author
author
author
author
author
author
author
author
author
author
author_browse Benitez, Sonia|||0000-0003-3565-0743
Bonaterra-Pastra, Anna|||0000-0002-1480-622X
Gil-Millan, Pedro
Ginel, Antonino|||0000-0002-8820-7545
Hernandez Guillamon, Maria Mar|||0000-0001-8844-0091
Miñambres, Inka|||0000-0002-0899-3938
Puig Grifol, Núria|||0000-0002-4699-3162
Pérez, Antonio|||0000-0001-5528-1143
Rives Jimenez, Jose|||0009-0001-5725-9270
Sánchez Quesada, José Luis|||0000-0003-0224-591X
Tauron, Manel|||0000-0002-5864-519X
author_facet Puig Grifol, Núria|||0000-0002-4699-3162
Rives Jimenez, Jose|||0009-0001-5725-9270
Gil-Millan, Pedro
Miñambres, Inka|||0000-0002-0899-3938
Ginel, Antonino|||0000-0002-8820-7545
Tauron, Manel|||0000-0002-5864-519X
Bonaterra-Pastra, Anna|||0000-0002-1480-622X
Hernandez Guillamon, Maria Mar|||0000-0001-8844-0091
Pérez, Antonio|||0000-0001-5528-1143
Sánchez Quesada, José Luis|||0000-0003-0224-591X
Benitez, Sonia|||0000-0003-3565-0743
author_role author
collection Dipòsit Digital de Documents de la UAB
description Diabetic patients present increased volume and functional alterations in epicardial adipose tissue (EAT). We aimed to analyze EAT from type 2 diabetic patients and the inflammatory and cytotoxic effects induced on cardiomyocytes. Furthermore, we analyzed the cardioprotective role of apolipoprotein J (apoJ). EAT explants were obtained from nondiabetic patients (ND), diabetic patients without coronary disease (DM), and DM patients with coronary disease (DM-C) after heart surgery. Morphological characteristics and gene expression were evaluated. Explants were cultured for 24 h and the content of nonesterified fatty acids (NEFA) and sphingolipid species in secretomes was evaluated by lipidomic analysis. Afterwards, secretomes were added to AC16 human cardiomyocytes for 24 h in the presence or absence of cardioprotective molecules (apoJ and HDL). Cytokine release and apoptosis/necrosis were assessed by ELISA and flow cytometry. The EAT from the diabetic samples showed altered expression of genes related to lipid accumulation, insulin resistance, and inflammation. The secretomes from the DM samples presented an increased ratio of pro/antiatherogenic ceramide (Cer) species, while those from DM-C contained the highest concentration of saturated NEFA. DM and DM-C secretomes promoted inflammation and cytotoxicity on AC16 cardiomyocytes. Exogenous Cer16:0, Cer24:1, and palmitic acid reproduced deleterious effects in AC16 cells. These effects were attenuated by exogenous apoJ. Diabetic secretomes promoted inflammation and cytotoxicity in cardiomyocytes. This effect was exacerbated in the secretomes of the DM-C samples. The increased content of specific NEFA and ceramide species seems to play a key role in inducing such deleterious effects, which are attenuated by apoJ.
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instname_str Universitat Autònoma de Barcelona
language eng
network_acronym_str ES
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oai_identifier_str oai:ddd.uab.cat:306970
publishDate 2024
publishDateSort 2024
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spelling Apolipoprotein J protects cardiomyocytes from lipid-mediated inflammation and cytotoxicity induced by the epicardial adipose tissue of diabetic patients Puig Grifol, Núria|||0000-0002-4699-3162 Rives Jimenez, Jose|||0009-0001-5725-9270 Gil-Millan, Pedro Miñambres, Inka|||0000-0002-0899-3938 Ginel, Antonino|||0000-0002-8820-7545 Tauron, Manel|||0000-0002-5864-519X Bonaterra-Pastra, Anna|||0000-0002-1480-622X Hernandez Guillamon, Maria Mar|||0000-0001-8844-0091 Pérez, Antonio|||0000-0001-5528-1143 Sánchez Quesada, José Luis|||0000-0003-0224-591X Benitez, Sonia|||0000-0003-3565-0743 Apolipoprotein J Apoptosis Ceramides Coronary artery disease Epicardial adipose tissue Fatty acids Inflammation Type 2 diabetes Diabetic patients present increased volume and functional alterations in epicardial adipose tissue (EAT). We aimed to analyze EAT from type 2 diabetic patients and the inflammatory and cytotoxic effects induced on cardiomyocytes. Furthermore, we analyzed the cardioprotective role of apolipoprotein J (apoJ). EAT explants were obtained from nondiabetic patients (ND), diabetic patients without coronary disease (DM), and DM patients with coronary disease (DM-C) after heart surgery. Morphological characteristics and gene expression were evaluated. Explants were cultured for 24 h and the content of nonesterified fatty acids (NEFA) and sphingolipid species in secretomes was evaluated by lipidomic analysis. Afterwards, secretomes were added to AC16 human cardiomyocytes for 24 h in the presence or absence of cardioprotective molecules (apoJ and HDL). Cytokine release and apoptosis/necrosis were assessed by ELISA and flow cytometry. The EAT from the diabetic samples showed altered expression of genes related to lipid accumulation, insulin resistance, and inflammation. The secretomes from the DM samples presented an increased ratio of pro/antiatherogenic ceramide (Cer) species, while those from DM-C contained the highest concentration of saturated NEFA. DM and DM-C secretomes promoted inflammation and cytotoxicity on AC16 cardiomyocytes. Exogenous Cer16:0, Cer24:1, and palmitic acid reproduced deleterious effects in AC16 cells. These effects were attenuated by exogenous apoJ. Diabetic secretomes promoted inflammation and cytotoxicity in cardiomyocytes. This effect was exacerbated in the secretomes of the DM-C samples. The increased content of specific NEFA and ceramide species seems to play a key role in inducing such deleterious effects, which are attenuated by apoJ. https://ddd.uab.cat/record/306970 https://dx.doi.org/urn:doi:10.1016/j.biopha.2024.116779
spellingShingle Apolipoprotein J protects cardiomyocytes from lipid-mediated inflammation and cytotoxicity induced by the epicardial adipose tissue of diabetic patients
Puig Grifol, Núria|||0000-0002-4699-3162
Apolipoprotein J
Apoptosis
Ceramides
Coronary artery disease
Epicardial adipose tissue
Fatty acids
Inflammation
Type 2 diabetes
title Apolipoprotein J protects cardiomyocytes from lipid-mediated inflammation and cytotoxicity induced by the epicardial adipose tissue of diabetic patients
title_full Apolipoprotein J protects cardiomyocytes from lipid-mediated inflammation and cytotoxicity induced by the epicardial adipose tissue of diabetic patients
title_fullStr Apolipoprotein J protects cardiomyocytes from lipid-mediated inflammation and cytotoxicity induced by the epicardial adipose tissue of diabetic patients
title_full_unstemmed Apolipoprotein J protects cardiomyocytes from lipid-mediated inflammation and cytotoxicity induced by the epicardial adipose tissue of diabetic patients
title_short Apolipoprotein J protects cardiomyocytes from lipid-mediated inflammation and cytotoxicity induced by the epicardial adipose tissue of diabetic patients
title_sort Apolipoprotein J protects cardiomyocytes from lipid-mediated inflammation and cytotoxicity induced by the epicardial adipose tissue of diabetic patients
topic Apolipoprotein J
Apoptosis
Ceramides
Coronary artery disease
Epicardial adipose tissue
Fatty acids
Inflammation
Type 2 diabetes
topic_facet Apolipoprotein J
Apoptosis
Ceramides
Coronary artery disease
Epicardial adipose tissue
Fatty acids
Inflammation
Type 2 diabetes
url https://ddd.uab.cat/record/306970
https://dx.doi.org/urn:doi:10.1016/j.biopha.2024.116779