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Epicardial Adipose Tissue–Derived Leptin Promotes Myocardial Injury in Metabolic Syndrome Rats Through PKC/NADPH Oxidase/ROS Pathway

BACKGROUND: The epicardial adipose tissue (EAT) of metabolic syndrome (MetS) is abnormally accumulated with dysfunctional secretion of adipokines, closely relating to cardiac dysfunction. The current study was designed to identify the effects of EAT‐derived leptin on the myocardium of MetS rats and...

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Autores principales: Chen, Hui, Liu, Lei, Li, Min, Zhu, Danjun, Tian, Gang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10492984/
https://www.ncbi.nlm.nih.gov/pubmed/37489731
http://dx.doi.org/10.1161/JAHA.123.029415
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author Chen, Hui
Liu, Lei
Li, Min
Zhu, Danjun
Tian, Gang
author_facet Chen, Hui
Liu, Lei
Li, Min
Zhu, Danjun
Tian, Gang
author_sort Chen, Hui
collection PubMed
description BACKGROUND: The epicardial adipose tissue (EAT) of metabolic syndrome (MetS) is abnormally accumulated with dysfunctional secretion of adipokines, closely relating to cardiac dysfunction. The current study was designed to identify the effects of EAT‐derived leptin on the myocardium of MetS rats and explore the potential molecular mechanisms. METHODS AND RESULTS: A MetS rat model was established in 8‐week‐old Wistar rats by a 12‐week high‐fat diet. MetS rats exhibited increased leptin secretion from EAT, cardiac hypertrophy, and diastolic dysfunction with preserved systolic function. The myocardium of MetS rats had abnormal structure, increased oxidative stress injury, and higher inflammatory factor levels, especially the subepicardial myocardium, which was correlated with the EAT‐derived leptin level but not the serum leptin. The EAT was separated from each group of rats to prepare EAT‐conditioned medium. H9C2 rat cardiomyoblasts were treated with EAT‐conditioned medium or leptin, plus various inhibitors. EAT‐derived leptin from MetS rats promoted mitochondrial oxidative stress and dysfunction, induced mitochondrial pathway apoptosis, and inhibited cell viability in H9C2 cardiomyoblasts via the protein kinase C/reduced nicotinamide adenine dinucleotide phosphate oxidase/reactive oxygen species (PKC/NADPH oxidase/ROS) pathway. EAT‐derived leptin from MetS rats stimulated inflammation in H9C2 cardiomyocytes by promoting activator protein 1 nuclear translocation via the PKC/NADPH oxidase/ROS pathway. Leptin promoted the interaction between p‐p47(phox) and gp91(phox) in H9C2 cardiomyocytes via protein kinase C, activating nicotinamide adenine dinucleotide phosphate oxidase, increasing reactive oxygen species generation, and inhibiting cell viability. CONCLUSIONS: EAT‐derived leptin induces MetS‐related myocardial injury through the following 2 cooperative ways via PKC/NADPH oxidase/ROS pathway: (1) inducing mitochondrial pathway apoptosis by promoting mitochondrial oxidative stress and dysfunction; and (2) stimulating inflammation by promoting activator protein 1 nuclear translocation.
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spelling pubmed-104929842023-09-11 Epicardial Adipose Tissue–Derived Leptin Promotes Myocardial Injury in Metabolic Syndrome Rats Through PKC/NADPH Oxidase/ROS Pathway Chen, Hui Liu, Lei Li, Min Zhu, Danjun Tian, Gang J Am Heart Assoc Original Research BACKGROUND: The epicardial adipose tissue (EAT) of metabolic syndrome (MetS) is abnormally accumulated with dysfunctional secretion of adipokines, closely relating to cardiac dysfunction. The current study was designed to identify the effects of EAT‐derived leptin on the myocardium of MetS rats and explore the potential molecular mechanisms. METHODS AND RESULTS: A MetS rat model was established in 8‐week‐old Wistar rats by a 12‐week high‐fat diet. MetS rats exhibited increased leptin secretion from EAT, cardiac hypertrophy, and diastolic dysfunction with preserved systolic function. The myocardium of MetS rats had abnormal structure, increased oxidative stress injury, and higher inflammatory factor levels, especially the subepicardial myocardium, which was correlated with the EAT‐derived leptin level but not the serum leptin. The EAT was separated from each group of rats to prepare EAT‐conditioned medium. H9C2 rat cardiomyoblasts were treated with EAT‐conditioned medium or leptin, plus various inhibitors. EAT‐derived leptin from MetS rats promoted mitochondrial oxidative stress and dysfunction, induced mitochondrial pathway apoptosis, and inhibited cell viability in H9C2 cardiomyoblasts via the protein kinase C/reduced nicotinamide adenine dinucleotide phosphate oxidase/reactive oxygen species (PKC/NADPH oxidase/ROS) pathway. EAT‐derived leptin from MetS rats stimulated inflammation in H9C2 cardiomyocytes by promoting activator protein 1 nuclear translocation via the PKC/NADPH oxidase/ROS pathway. Leptin promoted the interaction between p‐p47(phox) and gp91(phox) in H9C2 cardiomyocytes via protein kinase C, activating nicotinamide adenine dinucleotide phosphate oxidase, increasing reactive oxygen species generation, and inhibiting cell viability. CONCLUSIONS: EAT‐derived leptin induces MetS‐related myocardial injury through the following 2 cooperative ways via PKC/NADPH oxidase/ROS pathway: (1) inducing mitochondrial pathway apoptosis by promoting mitochondrial oxidative stress and dysfunction; and (2) stimulating inflammation by promoting activator protein 1 nuclear translocation. John Wiley and Sons Inc. 2023-07-25 /pmc/articles/PMC10492984/ /pubmed/37489731 http://dx.doi.org/10.1161/JAHA.123.029415 Text en © 2023 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Research
Chen, Hui
Liu, Lei
Li, Min
Zhu, Danjun
Tian, Gang
Epicardial Adipose Tissue–Derived Leptin Promotes Myocardial Injury in Metabolic Syndrome Rats Through PKC/NADPH Oxidase/ROS Pathway
title Epicardial Adipose Tissue–Derived Leptin Promotes Myocardial Injury in Metabolic Syndrome Rats Through PKC/NADPH Oxidase/ROS Pathway
title_full Epicardial Adipose Tissue–Derived Leptin Promotes Myocardial Injury in Metabolic Syndrome Rats Through PKC/NADPH Oxidase/ROS Pathway
title_fullStr Epicardial Adipose Tissue–Derived Leptin Promotes Myocardial Injury in Metabolic Syndrome Rats Through PKC/NADPH Oxidase/ROS Pathway
title_full_unstemmed Epicardial Adipose Tissue–Derived Leptin Promotes Myocardial Injury in Metabolic Syndrome Rats Through PKC/NADPH Oxidase/ROS Pathway
title_short Epicardial Adipose Tissue–Derived Leptin Promotes Myocardial Injury in Metabolic Syndrome Rats Through PKC/NADPH Oxidase/ROS Pathway
title_sort epicardial adipose tissue–derived leptin promotes myocardial injury in metabolic syndrome rats through pkc/nadph oxidase/ros pathway
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10492984/
https://www.ncbi.nlm.nih.gov/pubmed/37489731
http://dx.doi.org/10.1161/JAHA.123.029415
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