IRF4 in Skeletal Muscle Regulates Exercise Capacity via PTG/Glycogen Pathway
Abstract Exercise‐induced fatigue and exhaustion are interesting areas for many researchers. Muscle glycogen is critical for physical performance. However, how glycogen metabolism is manipulated during exercise is not very clear. The aim here is to assess the impact of interferon regulatory factor 4...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020-10-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202001502 |
| _version_ | 1818554261178417152 |
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| author | Xiaopeng Zhu Ting Yao Ru Wang Shanshan Guo Xin Wang Zhenqi Zhou Yan Zhang Xiaozhen Zhuo Ruitao Wang John Zhong Li Tiemin Liu Xingxing Kong |
| author_facet | Xiaopeng Zhu Ting Yao Ru Wang Shanshan Guo Xin Wang Zhenqi Zhou Yan Zhang Xiaozhen Zhuo Ruitao Wang John Zhong Li Tiemin Liu Xingxing Kong |
| author_sort | Xiaopeng Zhu |
| collection | DOAJ |
| description | Abstract Exercise‐induced fatigue and exhaustion are interesting areas for many researchers. Muscle glycogen is critical for physical performance. However, how glycogen metabolism is manipulated during exercise is not very clear. The aim here is to assess the impact of interferon regulatory factor 4 (IRF4) on skeletal muscle glycogen and subsequent regulation of exercise capacity. Skeletal muscle‐specific IRF4 knockout mice show normal body weight and insulin sensitivity, but better exercise capacity and increased glycogen content with unaltered triglyceride levels compared to control mice on chow diet. In contrast, mice overexpression of IRF4 displays decreased exercise capacity and lower glycogen content. Mechanistically, IRF4 regulates glycogen‐associated regulatory subunit protein targeting to glycogen (PTG) to manipulate glucose metabolism in skeletal muscle. Knockdown of PTG can reverse the effects imposed by the absence of IRF4 in vivo. These studies reveal a regulatory pathway including IRF4/PTG/glycogen synthesis on controlling exercise capacity. |
| first_indexed | 2024-12-12T09:37:02Z |
| format | Article |
| id | doaj.art-8bfa57e294984a20a29587a587a95ba9 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-12-12T09:37:02Z |
| publishDate | 2020-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-8bfa57e294984a20a29587a587a95ba92022-12-22T00:28:42ZengWileyAdvanced Science2198-38442020-10-01719n/an/a10.1002/advs.202001502IRF4 in Skeletal Muscle Regulates Exercise Capacity via PTG/Glycogen PathwayXiaopeng Zhu0Ting Yao1Ru Wang2Shanshan Guo3Xin Wang4Zhenqi Zhou5Yan Zhang6Xiaozhen Zhuo7Ruitao Wang8John Zhong Li9Tiemin Liu10Xingxing Kong11Division of Pediatric Endocrinology Department of Pediatrics UCLA Children's Discovery and Innovation Institute David Geffen School of Medicine at UCLA Los Angeles CA 90095 USADivision of Pediatric Endocrinology Department of Pediatrics UCLA Children's Discovery and Innovation Institute David Geffen School of Medicine at UCLA Los Angeles CA 90095 USASchool of Kinesiology Key Laboratory of Exercise and Health Sciences of Ministry of Education Shanghai University of Sport Shanghai 200438 P. R. ChinaSchool of Kinesiology Key Laboratory of Exercise and Health Sciences of Ministry of Education Shanghai University of Sport Shanghai 200438 P. R. ChinaDivision of Pediatric Endocrinology Department of Pediatrics UCLA Children's Discovery and Innovation Institute David Geffen School of Medicine at UCLA Los Angeles CA 90095 USADepartment of Medicine Division of Endocrinology, Diabetes and Hypertension David Geffen School of Medicine University of California Los Angeles CA 90095 USASchool of Life Sciences Fudan University Shanghai 200032 P. R. ChinaDepartment of Cardiology The First Affiliated Hospital Xi'an Jiaotong University Xi'an Shanxi 710061 P. R. ChinaDepartment of Internal Medicine Harbin Medical University Cancer Hospital Harbin Medical University No. 150 Haping ST, Nangang District Harbin Heilongjiang 150081 P. R. ChinaThe Key Laboratory of Rare Metabolic Disease Department of Biochemistry and Molecular Biology The Key Laboratory of Human Functional Genomics of Jiangsu Province Nanjing Medical University Nanjing Jiangsu 211166 P. R. ChinaState Key Laboratory of Genetic Engineering Department of Endocrinology and Metabolism and School of Life Sciences Zhongshan Hospital Fudan University Shanghai 200032 P. R. ChinaDivision of Pediatric Endocrinology Department of Pediatrics UCLA Children's Discovery and Innovation Institute David Geffen School of Medicine at UCLA Los Angeles CA 90095 USAAbstract Exercise‐induced fatigue and exhaustion are interesting areas for many researchers. Muscle glycogen is critical for physical performance. However, how glycogen metabolism is manipulated during exercise is not very clear. The aim here is to assess the impact of interferon regulatory factor 4 (IRF4) on skeletal muscle glycogen and subsequent regulation of exercise capacity. Skeletal muscle‐specific IRF4 knockout mice show normal body weight and insulin sensitivity, but better exercise capacity and increased glycogen content with unaltered triglyceride levels compared to control mice on chow diet. In contrast, mice overexpression of IRF4 displays decreased exercise capacity and lower glycogen content. Mechanistically, IRF4 regulates glycogen‐associated regulatory subunit protein targeting to glycogen (PTG) to manipulate glucose metabolism in skeletal muscle. Knockdown of PTG can reverse the effects imposed by the absence of IRF4 in vivo. These studies reveal a regulatory pathway including IRF4/PTG/glycogen synthesis on controlling exercise capacity.https://doi.org/10.1002/advs.202001502exercise capacityglycogenIRF4PTGskeletal muscle |
| spellingShingle | Xiaopeng Zhu Ting Yao Ru Wang Shanshan Guo Xin Wang Zhenqi Zhou Yan Zhang Xiaozhen Zhuo Ruitao Wang John Zhong Li Tiemin Liu Xingxing Kong IRF4 in Skeletal Muscle Regulates Exercise Capacity via PTG/Glycogen Pathway Advanced Science exercise capacity glycogen IRF4 PTG skeletal muscle |
| title | IRF4 in Skeletal Muscle Regulates Exercise Capacity via PTG/Glycogen Pathway |
| title_full | IRF4 in Skeletal Muscle Regulates Exercise Capacity via PTG/Glycogen Pathway |
| title_fullStr | IRF4 in Skeletal Muscle Regulates Exercise Capacity via PTG/Glycogen Pathway |
| title_full_unstemmed | IRF4 in Skeletal Muscle Regulates Exercise Capacity via PTG/Glycogen Pathway |
| title_short | IRF4 in Skeletal Muscle Regulates Exercise Capacity via PTG/Glycogen Pathway |
| title_sort | irf4 in skeletal muscle regulates exercise capacity via ptg glycogen pathway |
| topic | exercise capacity glycogen IRF4 PTG skeletal muscle |
| url | https://doi.org/10.1002/advs.202001502 |
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