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 e...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-08-01
|
| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.123.029415 |
| _version_ | 1797738386916638720 |
|---|---|
| author | Hui Chen Lei Liu Min Li Danjun Zhu Gang Tian |
| author_facet | Hui Chen Lei Liu Min Li Danjun Zhu Gang Tian |
| author_sort | Hui Chen |
| collection | DOAJ |
| 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‐p47phox and gp91phox 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. |
| first_indexed | 2024-03-12T13:43:02Z |
| format | Article |
| id | doaj.art-5aff82878efe45bd9348706355c345b9 |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-03-12T13:43:02Z |
| publishDate | 2023-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-5aff82878efe45bd9348706355c345b92023-08-23T10:41:23ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802023-08-01121510.1161/JAHA.123.029415Epicardial Adipose Tissue–Derived Leptin Promotes Myocardial Injury in Metabolic Syndrome Rats Through PKC/NADPH Oxidase/ROS PathwayHui Chen0Lei Liu1Min Li2Danjun Zhu3Gang Tian4Heart Center of Henan Provincial People’s Hospital, Central China Fuwai Hospital Central China Fuwai Hospital of Zhengzhou University Zhengzhou Henan ChinaDepartment of Cardiology The First Affiliated Hospital of Xi’an Jiao Tong University Xi’an Shaanxi ChinaDepartment of Cardiology The First Affiliated Hospital of Xi’an Jiao Tong University Xi’an Shaanxi ChinaDepartment of Cardiology The First Affiliated Hospital of Xi’an Jiao Tong University Xi’an Shaanxi ChinaDepartment of Cardiology The First Affiliated Hospital of Xi’an Jiao Tong University Xi’an Shaanxi ChinaBackground 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‐p47phox and gp91phox 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.https://www.ahajournals.org/doi/10.1161/JAHA.123.029415epicardial adipose tissueleptinmetabolic syndromemyocardial injury |
| spellingShingle | Hui Chen Lei Liu Min Li Danjun Zhu Gang Tian Epicardial Adipose Tissue–Derived Leptin Promotes Myocardial Injury in Metabolic Syndrome Rats Through PKC/NADPH Oxidase/ROS Pathway Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease epicardial adipose tissue leptin metabolic syndrome myocardial injury |
| 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 | epicardial adipose tissue leptin metabolic syndrome myocardial injury |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.123.029415 |
| work_keys_str_mv | AT huichen epicardialadiposetissuederivedleptinpromotesmyocardialinjuryinmetabolicsyndromeratsthroughpkcnadphoxidaserospathway AT leiliu epicardialadiposetissuederivedleptinpromotesmyocardialinjuryinmetabolicsyndromeratsthroughpkcnadphoxidaserospathway AT minli epicardialadiposetissuederivedleptinpromotesmyocardialinjuryinmetabolicsyndromeratsthroughpkcnadphoxidaserospathway AT danjunzhu epicardialadiposetissuederivedleptinpromotesmyocardialinjuryinmetabolicsyndromeratsthroughpkcnadphoxidaserospathway AT gangtian epicardialadiposetissuederivedleptinpromotesmyocardialinjuryinmetabolicsyndromeratsthroughpkcnadphoxidaserospathway |