HIF-1α Negatively Regulates Irisin Expression Which Involves in Muscle Atrophy Induced by Hypoxia

Exposure to high altitude environment leads to skeletal muscle atrophy. As a hormone secreted by skeletal muscles after exercise, irisin contributes to promoting muscle regeneration and ameliorating skeletal muscle atrophy, but its role in hypoxia-induced skeletal muscle atrophy is still unclear. Ou...

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Main Authors: Shiqiang Liu, Pengyu Fu, Kaiting Ning, Rui Wang, Baoqiang Yang, Jiahui Chen, Huiyun Xu
Format: Article
Language:English
Published: MDPI AG 2022-01-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/2/887
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author Shiqiang Liu
Pengyu Fu
Kaiting Ning
Rui Wang
Baoqiang Yang
Jiahui Chen
Huiyun Xu
author_facet Shiqiang Liu
Pengyu Fu
Kaiting Ning
Rui Wang
Baoqiang Yang
Jiahui Chen
Huiyun Xu
author_sort Shiqiang Liu
collection DOAJ
description Exposure to high altitude environment leads to skeletal muscle atrophy. As a hormone secreted by skeletal muscles after exercise, irisin contributes to promoting muscle regeneration and ameliorating skeletal muscle atrophy, but its role in hypoxia-induced skeletal muscle atrophy is still unclear. Our results showed that 4 w of hypoxia exposure significantly reduced body weight and gastrocnemius muscle mass of mice, as well as grip strength and the duration time of treadmill exercise. Hypoxic treatment increased HIF-1α expression and decreased both the circulation level of irisin and its precursor protein FNDC5 expression in skeletal muscle. In in vitro, CoCl<sub>2</sub>-induced chemical hypoxia and 1% O<sub>2</sub> ambient hypoxia both reduced FNDC5, along with the increase in HIF-1α. Moreover, the decline in the area and diameter of myotubes caused by hypoxia were rescued by inhibiting HIF-1α via YC-1. Collectively, our research indicated that FNDC5/irisin was negatively regulated by HIF-1α and could participate in the regulation of muscle atrophy caused by hypoxia.
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spelling doaj.art-0d4e6c6034bb41eb8f76a63161df886c2023-11-23T14:06:02ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-01-0123288710.3390/ijms23020887HIF-1α Negatively Regulates Irisin Expression Which Involves in Muscle Atrophy Induced by HypoxiaShiqiang Liu0Pengyu Fu1Kaiting Ning2Rui Wang3Baoqiang Yang4Jiahui Chen5Huiyun Xu6Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi’an 710072, ChinaDepartment of Physical Education, Northwestern Polytechnical University, Xi’an 710072, ChinaKey Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi’an 710072, ChinaKey Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi’an 710072, ChinaKey Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi’an 710072, ChinaKey Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi’an 710072, ChinaKey Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi’an 710072, ChinaExposure to high altitude environment leads to skeletal muscle atrophy. As a hormone secreted by skeletal muscles after exercise, irisin contributes to promoting muscle regeneration and ameliorating skeletal muscle atrophy, but its role in hypoxia-induced skeletal muscle atrophy is still unclear. Our results showed that 4 w of hypoxia exposure significantly reduced body weight and gastrocnemius muscle mass of mice, as well as grip strength and the duration time of treadmill exercise. Hypoxic treatment increased HIF-1α expression and decreased both the circulation level of irisin and its precursor protein FNDC5 expression in skeletal muscle. In in vitro, CoCl<sub>2</sub>-induced chemical hypoxia and 1% O<sub>2</sub> ambient hypoxia both reduced FNDC5, along with the increase in HIF-1α. Moreover, the decline in the area and diameter of myotubes caused by hypoxia were rescued by inhibiting HIF-1α via YC-1. Collectively, our research indicated that FNDC5/irisin was negatively regulated by HIF-1α and could participate in the regulation of muscle atrophy caused by hypoxia.https://www.mdpi.com/1422-0067/23/2/887hypoxiamuscle atrophyHIF-1αirisinFNDC5
spellingShingle Shiqiang Liu
Pengyu Fu
Kaiting Ning
Rui Wang
Baoqiang Yang
Jiahui Chen
Huiyun Xu
HIF-1α Negatively Regulates Irisin Expression Which Involves in Muscle Atrophy Induced by Hypoxia
International Journal of Molecular Sciences
hypoxia
muscle atrophy
HIF-1α
irisin
FNDC5
title HIF-1α Negatively Regulates Irisin Expression Which Involves in Muscle Atrophy Induced by Hypoxia
title_full HIF-1α Negatively Regulates Irisin Expression Which Involves in Muscle Atrophy Induced by Hypoxia
title_fullStr HIF-1α Negatively Regulates Irisin Expression Which Involves in Muscle Atrophy Induced by Hypoxia
title_full_unstemmed HIF-1α Negatively Regulates Irisin Expression Which Involves in Muscle Atrophy Induced by Hypoxia
title_short HIF-1α Negatively Regulates Irisin Expression Which Involves in Muscle Atrophy Induced by Hypoxia
title_sort hif 1α negatively regulates irisin expression which involves in muscle atrophy induced by hypoxia
topic hypoxia
muscle atrophy
HIF-1α
irisin
FNDC5
url https://www.mdpi.com/1422-0067/23/2/887
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