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 para...

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Autores principales:	Ping Wang, Chaodi Luo, Danjun Zhu, Yan Song, Lifei Cao, Hui Luan, Lan Gao, Shuping Zheng, Hao Li, Gang Tian
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	leptin myocardial apoptosis Na+/K+‐ATPase obesity paracrine pericardial adipose tissue Diseases of the circulatory (Cardiovascular) system RC666-701
Acceso en línea:	https://doaj.org/article/08013084feff492f963a9a6cb062a789
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spelling	oai:doaj.org-article:08013084feff492f963a9a6cb062a7892021-11-23T11:36:36ZPericardial 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 Pathway10.1161/JAHA.121.0213692047-9980https://doaj.org/article/08013084feff492f963a9a6cb062a7892021-09-01T00:00:00Zhttps://www.ahajournals.org/doi/10.1161/JAHA.121.021369https://doaj.org/toc/2047-9980Background 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.Ping WangChaodi LuoDanjun ZhuYan SongLifei CaoHui LuanLan GaoShuping ZhengHao LiGang TianWileyarticleleptinmyocardial apoptosisNa+/K+‐ATPaseobesityparacrinepericardial adipose tissueDiseases of the circulatory (Cardiovascular) systemRC666-701ENJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, Vol 10, Iss 18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	leptin myocardial apoptosis Na+/K+‐ATPase obesity paracrine pericardial adipose tissue Diseases of the circulatory (Cardiovascular) system RC666-701
spellingShingle	leptin myocardial apoptosis Na+/K+‐ATPase obesity paracrine pericardial adipose tissue Diseases of the circulatory (Cardiovascular) system RC666-701 Ping Wang Chaodi Luo Danjun Zhu Yan Song Lifei Cao Hui Luan Lan Gao Shuping Zheng Hao Li Gang Tian 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
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	article
author	Ping Wang Chaodi Luo Danjun Zhu Yan Song Lifei Cao Hui Luan Lan Gao Shuping Zheng Hao Li Gang Tian
author_facet	Ping Wang Chaodi Luo Danjun Zhu Yan Song Lifei Cao Hui Luan Lan Gao Shuping Zheng Hao Li Gang Tian
author_sort	Ping Wang
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_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_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_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
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/08013084feff492f963a9a6cb062a789
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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

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