Exercise Enhanced Cardiac Function in Mice With Radiation-Induced Heart Disease via the FNDC5/Irisin-Dependent Mitochondrial Turnover Pathway

Background: Despite the development of radiation therapy (RT) techniques, concern regarding the serious and irreversible heart injury induced by RT has grown due to the lack of early intervention measures. Although exercise can act as an effective and economic nonpharmacologic strategy to combat fat...

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Autores principales:	Wuyang He, Yinghong Tang, Chunqiu Li, Xiaoyue Zhang, Shunping Huang, Benxu Tan, Zhenzhou Yang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	FNDC5 irisin radiation therapy heart aerobic exercise Physiology QP1-981
Acceso en línea:	https://doaj.org/article/f02171c8c55142ca9b80ab13b2af2265
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spelling	oai:doaj.org-article:f02171c8c55142ca9b80ab13b2af22652021-11-11T09:41:11ZExercise Enhanced Cardiac Function in Mice With Radiation-Induced Heart Disease via the FNDC5/Irisin-Dependent Mitochondrial Turnover Pathway1664-042X10.3389/fphys.2021.739485https://doaj.org/article/f02171c8c55142ca9b80ab13b2af22652021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphys.2021.739485/fullhttps://doaj.org/toc/1664-042XBackground: Despite the development of radiation therapy (RT) techniques, concern regarding the serious and irreversible heart injury induced by RT has grown due to the lack of early intervention measures. Although exercise can act as an effective and economic nonpharmacologic strategy to combat fatigue and improve quality of life for cancer survivors, limited data on its application in radiation-induced heart disease (RIHD) and the underlying molecular mechanism are available.Methods: Fifteen young adult male mice were enrolled in this study and divided into 3 groups (including exercised RIHD group, sedentary RIHD group, and controls; n =5 samples/group). While the mice in the control group were kept in cages without irradiation, those in the exercised RIHD group underwent 3weeks of aerobic exercise on the treadmill after radiotherapy. At the end of the 3rd week following RT, FNDC5/irisin expression, cardiac function, aerobic fitness, cardiomyocyte apoptosis, mitochondrial function, and mitochondrial turnover in the myocardium were assessed to identify the protective role of exercise in RIHD and investigate the potential mechanism.Results: While sedentary RIHD group had impaired cardiac function and aerobic fitness than controls, the exercised RIHD mice had improved cardiac function and aerobic fitness, elevated ATP production and the mitochondrial protein content, decreased mitochondrial length, and increased formation of mitophagosomes compared with sedentary RIHD mice. These changes were accompanied by the elevated expression of FNDC5/irisin, a fission marker (DRP1) and mitophagy markers (PINK1 and LC3B) in exercised RIHD group than that of sedentary RIHD group, but the expression of biogenesis (TFAM) and fusion (MFN2) markers was not significantly changed.Conclusion: Exercise could enhance cardiac function and aerobic fitness in RIHD mice partly through an autocrine mechanism via FNDC5/irisin, in which autophagy was selectively activated, suggesting that FNDC5/irisin may act as an intervening target to prevent the development of RIHD.Wuyang HeYinghong TangChunqiu LiXiaoyue ZhangShunping HuangBenxu TanZhenzhou YangFrontiers Media S.A.articleFNDC5irisinradiation therapyheartaerobic exercisePhysiologyQP1-981ENFrontiers in Physiology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	FNDC5 irisin radiation therapy heart aerobic exercise Physiology QP1-981
spellingShingle	FNDC5 irisin radiation therapy heart aerobic exercise Physiology QP1-981 Wuyang He Yinghong Tang Chunqiu Li Xiaoyue Zhang Shunping Huang Benxu Tan Zhenzhou Yang Exercise Enhanced Cardiac Function in Mice With Radiation-Induced Heart Disease via the FNDC5/Irisin-Dependent Mitochondrial Turnover Pathway
description	Background: Despite the development of radiation therapy (RT) techniques, concern regarding the serious and irreversible heart injury induced by RT has grown due to the lack of early intervention measures. Although exercise can act as an effective and economic nonpharmacologic strategy to combat fatigue and improve quality of life for cancer survivors, limited data on its application in radiation-induced heart disease (RIHD) and the underlying molecular mechanism are available.Methods: Fifteen young adult male mice were enrolled in this study and divided into 3 groups (including exercised RIHD group, sedentary RIHD group, and controls; n =5 samples/group). While the mice in the control group were kept in cages without irradiation, those in the exercised RIHD group underwent 3weeks of aerobic exercise on the treadmill after radiotherapy. At the end of the 3rd week following RT, FNDC5/irisin expression, cardiac function, aerobic fitness, cardiomyocyte apoptosis, mitochondrial function, and mitochondrial turnover in the myocardium were assessed to identify the protective role of exercise in RIHD and investigate the potential mechanism.Results: While sedentary RIHD group had impaired cardiac function and aerobic fitness than controls, the exercised RIHD mice had improved cardiac function and aerobic fitness, elevated ATP production and the mitochondrial protein content, decreased mitochondrial length, and increased formation of mitophagosomes compared with sedentary RIHD mice. These changes were accompanied by the elevated expression of FNDC5/irisin, a fission marker (DRP1) and mitophagy markers (PINK1 and LC3B) in exercised RIHD group than that of sedentary RIHD group, but the expression of biogenesis (TFAM) and fusion (MFN2) markers was not significantly changed.Conclusion: Exercise could enhance cardiac function and aerobic fitness in RIHD mice partly through an autocrine mechanism via FNDC5/irisin, in which autophagy was selectively activated, suggesting that FNDC5/irisin may act as an intervening target to prevent the development of RIHD.
format	article
author	Wuyang He Yinghong Tang Chunqiu Li Xiaoyue Zhang Shunping Huang Benxu Tan Zhenzhou Yang
author_facet	Wuyang He Yinghong Tang Chunqiu Li Xiaoyue Zhang Shunping Huang Benxu Tan Zhenzhou Yang
author_sort	Wuyang He
title	Exercise Enhanced Cardiac Function in Mice With Radiation-Induced Heart Disease via the FNDC5/Irisin-Dependent Mitochondrial Turnover Pathway
title_short	Exercise Enhanced Cardiac Function in Mice With Radiation-Induced Heart Disease via the FNDC5/Irisin-Dependent Mitochondrial Turnover Pathway
title_full	Exercise Enhanced Cardiac Function in Mice With Radiation-Induced Heart Disease via the FNDC5/Irisin-Dependent Mitochondrial Turnover Pathway
title_fullStr	Exercise Enhanced Cardiac Function in Mice With Radiation-Induced Heart Disease via the FNDC5/Irisin-Dependent Mitochondrial Turnover Pathway
title_full_unstemmed	Exercise Enhanced Cardiac Function in Mice With Radiation-Induced Heart Disease via the FNDC5/Irisin-Dependent Mitochondrial Turnover Pathway
title_sort	exercise enhanced cardiac function in mice with radiation-induced heart disease via the fndc5/irisin-dependent mitochondrial turnover pathway
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/f02171c8c55142ca9b80ab13b2af2265
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Exercise Enhanced Cardiac Function in Mice With Radiation-Induced Heart Disease via the FNDC5/Irisin-Dependent Mitochondrial Turnover Pathway

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