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Pericardial Adipose Tissue–Derived Leptin Promotes Myocardial Apoptosis in High‐Fat Diet–Induced Obese Rats Through Janus Kinase 2/Reactive Oxygen Species/Na+/K+‐ATPase Signaling Pathway
BACKGROUND: Pathophysiologic mechanisms underlying cardiac structural and functional changes in obesity are complex and linked to adipocytokines released from pericardial adipose tissue (PAT) and cardiomyocyte apoptosis. Although leptin is involved in various pathological conditions, its role in par...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8649551/ https://www.ncbi.nlm.nih.gov/pubmed/34482701 http://dx.doi.org/10.1161/JAHA.121.021369 |
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author | Wang, Ping Luo, Chaodi Zhu, Danjun Song, Yan Cao, Lifei Luan, Hui Gao, Lan Zheng, Shuping Li, Hao Tian, Gang |
author_facet | Wang, Ping Luo, Chaodi Zhu, Danjun Song, Yan Cao, Lifei Luan, Hui Gao, Lan Zheng, Shuping Li, Hao Tian, Gang |
author_sort | Wang, Ping |
collection | PubMed |
description | BACKGROUND: Pathophysiologic mechanisms underlying cardiac structural and functional changes in obesity are complex and linked to adipocytokines released from pericardial adipose tissue (PAT) and cardiomyocyte apoptosis. Although leptin is involved in various pathological conditions, its role in paracrine action of pericardial adipose tissue on myocardial apoptosis remains unknown. This study was designed to investigate the role of PAT‐derived leptin on myocardial apoptosis in high‐fat diet–induced obese rats. METHODS AND RESULTS: Hearts were isolated from lean or high‐fat diet–induced obese Wistar rats for myocardial remodeling studies. Obese rats had abnormal myocardial structure, diastolic dysfunction, greatly elevated cardiac apoptosis, enhanced cardiac fibrosis, and increased oxidative stress level. ELISA detected significantly higher than circulating leptin level in PAT of obese, but not lean, rats. Western blot and immunohistochemical analyses demonstrated increased leptin receptor density in obese hearts. H9c2 cardiomyoblasts, after being exposed to PAT‐conditioned medium of obese rats, exhibited pronounced reactive oxygen species–mediated apoptosis, which was partially reversed by leptin antagonist. Moreover, leptin derived from PAT of obese rats inhibited Na(+)/K(+)‐ATPase activity of H9c2 cells through stimulating reactive oxygen species, thereby activating calcium‐dependent apoptosis. Pretreatment with specific inhibitors revealed that Janus kinase 2/signal transducer and activator of transcription 3 and phosphoinositide 3‐kinase/protein kinase B signaling pathways were involved in leptin‐induced myocardial apoptosis. CONCLUSIONS: PAT‐derived leptin induces myocardial apoptosis in high‐fat diet–induced obese rats via activating Janus kinase 2/signal transducer and activator of transcription 3/reactive oxygen species signaling pathway and inhibiting its downstream Na(+)/K(+)‐ATPase activity. |
format | Online Article Text |
id | pubmed-8649551 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-86495512021-12-20 Pericardial Adipose Tissue–Derived Leptin Promotes Myocardial Apoptosis in High‐Fat Diet–Induced Obese Rats Through Janus Kinase 2/Reactive Oxygen Species/Na+/K+‐ATPase Signaling Pathway Wang, Ping Luo, Chaodi Zhu, Danjun Song, Yan Cao, Lifei Luan, Hui Gao, Lan Zheng, Shuping Li, Hao Tian, Gang J Am Heart Assoc Original Research BACKGROUND: Pathophysiologic mechanisms underlying cardiac structural and functional changes in obesity are complex and linked to adipocytokines released from pericardial adipose tissue (PAT) and cardiomyocyte apoptosis. Although leptin is involved in various pathological conditions, its role in paracrine action of pericardial adipose tissue on myocardial apoptosis remains unknown. This study was designed to investigate the role of PAT‐derived leptin on myocardial apoptosis in high‐fat diet–induced obese rats. METHODS AND RESULTS: Hearts were isolated from lean or high‐fat diet–induced obese Wistar rats for myocardial remodeling studies. Obese rats had abnormal myocardial structure, diastolic dysfunction, greatly elevated cardiac apoptosis, enhanced cardiac fibrosis, and increased oxidative stress level. ELISA detected significantly higher than circulating leptin level in PAT of obese, but not lean, rats. Western blot and immunohistochemical analyses demonstrated increased leptin receptor density in obese hearts. H9c2 cardiomyoblasts, after being exposed to PAT‐conditioned medium of obese rats, exhibited pronounced reactive oxygen species–mediated apoptosis, which was partially reversed by leptin antagonist. Moreover, leptin derived from PAT of obese rats inhibited Na(+)/K(+)‐ATPase activity of H9c2 cells through stimulating reactive oxygen species, thereby activating calcium‐dependent apoptosis. Pretreatment with specific inhibitors revealed that Janus kinase 2/signal transducer and activator of transcription 3 and phosphoinositide 3‐kinase/protein kinase B signaling pathways were involved in leptin‐induced myocardial apoptosis. CONCLUSIONS: PAT‐derived leptin induces myocardial apoptosis in high‐fat diet–induced obese rats via activating Janus kinase 2/signal transducer and activator of transcription 3/reactive oxygen species signaling pathway and inhibiting its downstream Na(+)/K(+)‐ATPase activity. John Wiley and Sons Inc. 2021-09-06 /pmc/articles/PMC8649551/ /pubmed/34482701 http://dx.doi.org/10.1161/JAHA.121.021369 Text en © 2021 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 Wang, Ping Luo, Chaodi Zhu, Danjun Song, Yan Cao, Lifei Luan, Hui Gao, Lan Zheng, Shuping Li, Hao Tian, Gang Pericardial Adipose Tissue–Derived Leptin Promotes Myocardial Apoptosis in High‐Fat Diet–Induced Obese Rats Through Janus Kinase 2/Reactive Oxygen Species/Na+/K+‐ATPase Signaling Pathway |
title | Pericardial Adipose Tissue–Derived Leptin Promotes Myocardial Apoptosis in High‐Fat Diet–Induced Obese Rats Through Janus Kinase 2/Reactive Oxygen Species/Na+/K+‐ATPase Signaling Pathway |
title_full | Pericardial Adipose Tissue–Derived Leptin Promotes Myocardial Apoptosis in High‐Fat Diet–Induced Obese Rats Through Janus Kinase 2/Reactive Oxygen Species/Na+/K+‐ATPase Signaling Pathway |
title_fullStr | Pericardial Adipose Tissue–Derived Leptin Promotes Myocardial Apoptosis in High‐Fat Diet–Induced Obese Rats Through Janus Kinase 2/Reactive Oxygen Species/Na+/K+‐ATPase Signaling Pathway |
title_full_unstemmed | Pericardial Adipose Tissue–Derived Leptin Promotes Myocardial Apoptosis in High‐Fat Diet–Induced Obese Rats Through Janus Kinase 2/Reactive Oxygen Species/Na+/K+‐ATPase Signaling Pathway |
title_short | Pericardial Adipose Tissue–Derived Leptin Promotes Myocardial Apoptosis in High‐Fat Diet–Induced Obese Rats Through Janus Kinase 2/Reactive Oxygen Species/Na+/K+‐ATPase Signaling Pathway |
title_sort | pericardial adipose tissue–derived leptin promotes myocardial apoptosis in high‐fat diet–induced obese rats through janus kinase 2/reactive oxygen species/na+/k+‐atpase signaling pathway |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8649551/ https://www.ncbi.nlm.nih.gov/pubmed/34482701 http://dx.doi.org/10.1161/JAHA.121.021369 |
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