Exercise enhances cardiac function by improving mitochondrial dysfunction and maintaining energy homoeostasis in the development of diabetic cardiomyopathy
Diabetic cardiomyopathy (DCM) is a major cause of morbidity and mortality in diabetic patients. Reactive oxygen species (ROS) produced by oxidative stress play an important role in the development of DCM. DCM involves abnormal energy metabolism, thereby reducing energy production. Exercise has been...
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| Veröffentlicht in: | Journal of molecular medicine (Berlin, Germany) Germany), 2020-02, Vol.98 (2), p.245-261 |
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| creator | Wang, Shawn Yongshun Zhu, Siyu Wu, Jian Zhang, Maomao Xu, Yousheng Xu, Wei Cui, Jinjin Yu, Bo Cao, Wei Liu, Jingjin |
| description | Diabetic cardiomyopathy (DCM) is a major cause of morbidity and mortality in diabetic patients. Reactive oxygen species (ROS) produced by oxidative stress play an important role in the development of DCM. DCM involves abnormal energy metabolism, thereby reducing energy production. Exercise has been reported to be effective in protecting the heart against ROS accumulation during the development of DCM. We hypothesize that the AMPK/PGC-1α axis may play a crucial role in exercise-induced bioenergetic metabolism and aerobic respiration on oxidative stress parameters in the development of diabetic cardiomyopathy. Using a streptozotocin/high-fat diet mouse to generate a diabetic model, our aim was to evaluate the effects of exercise on the cardiac function, mitochondrial oxidative capacity, mitochondrial function, and cardiac expression of PGC-1α. Mice fed a high-fat diet were given MO-siPGC-1α or treated with AMPK inhibitor. Mitochondrial structure and effects of switching between the Warburg effect and aerobic respiration were analysed. Exercise improved blood pressure and systolic dysfunction in diabetic mouse hearts. The beneficial effects of exercise were also observed in a mitochondrial function study, as reflected by an enhanced oxidative phosphorylation level, increased membrane potential, and decreased ROS level and oxygen consumption. On the other hand, depletion of PGC-1α attenuated the effects of exercise on the enhancement of mitochondrial function. In addition, PGC-1α may be responsible for reversing the Warburg effect to aerobic respiration, thus enhancing mitochondrial metabolism and energy homoeostasis. In this study, we demonstrate the protective effects of exercise on shifting energy metabolism from fatty acid oxidation to glucose oxidation in an established diabetic stage. These data suggest that exercise is effective at ameliorating diabetic cardiomyopathy by improving mitochondrial function and reducing metabolic disturbances. |
| doi_str_mv | 10.1007/s00109-019-01861-2 |
| format | Article |
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Reactive oxygen species (ROS) produced by oxidative stress play an important role in the development of DCM. DCM involves abnormal energy metabolism, thereby reducing energy production. Exercise has been reported to be effective in protecting the heart against ROS accumulation during the development of DCM. We hypothesize that the AMPK/PGC-1α axis may play a crucial role in exercise-induced bioenergetic metabolism and aerobic respiration on oxidative stress parameters in the development of diabetic cardiomyopathy. Using a streptozotocin/high-fat diet mouse to generate a diabetic model, our aim was to evaluate the effects of exercise on the cardiac function, mitochondrial oxidative capacity, mitochondrial function, and cardiac expression of PGC-1α. Mice fed a high-fat diet were given MO-siPGC-1α or treated with AMPK inhibitor. Mitochondrial structure and effects of switching between the Warburg effect and aerobic respiration were analysed. Exercise improved blood pressure and systolic dysfunction in diabetic mouse hearts. The beneficial effects of exercise were also observed in a mitochondrial function study, as reflected by an enhanced oxidative phosphorylation level, increased membrane potential, and decreased ROS level and oxygen consumption. On the other hand, depletion of PGC-1α attenuated the effects of exercise on the enhancement of mitochondrial function. In addition, PGC-1α may be responsible for reversing the Warburg effect to aerobic respiration, thus enhancing mitochondrial metabolism and energy homoeostasis. In this study, we demonstrate the protective effects of exercise on shifting energy metabolism from fatty acid oxidation to glucose oxidation in an established diabetic stage. These data suggest that exercise is effective at ameliorating diabetic cardiomyopathy by improving mitochondrial function and reducing metabolic disturbances.</description><identifier>ISSN: 0946-2716</identifier><identifier>EISSN: 1432-1440</identifier><identifier>DOI: 10.1007/s00109-019-01861-2</identifier><identifier>PMID: 31897508</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Adenosine Triphosphate - metabolism ; Aerobic respiration ; AMP-Activated Protein Kinases ; Animals ; Biomedical and Life Sciences ; Biomedicine ; Blood Pressure ; Cardiac function ; Cardiomyopathy ; Cells, Cultured ; Diabetes ; Diabetes mellitus ; Diabetes Mellitus, Experimental - metabolism ; Diabetes Mellitus, Experimental - physiopathology ; Diabetes Mellitus, Type 2 - metabolism ; Diabetes Mellitus, Type 2 - physiopathology ; Diabetic Cardiomyopathies - metabolism ; Diabetic Cardiomyopathies - physiopathology ; Energy Metabolism ; Exercise ; Glucose - metabolism ; Heart diseases ; High fat diet ; Homeostasis ; Human Genetics ; Internal Medicine ; Lactic Acid - metabolism ; Male ; Membrane potential ; Membrane Potential, Mitochondrial ; Metabolism ; Mice, Inbred C57BL ; Mitochondria ; Mitochondria, Heart - physiology ; Molecular Medicine ; Morbidity ; Myocytes, Cardiac - metabolism ; Original Article ; Oxidation ; Oxidative phosphorylation ; Oxidative stress ; Oxygen consumption ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - metabolism ; Phosphorylation ; Physical Conditioning, Animal ; Physical fitness ; Reactive oxygen species ; Reactive Oxygen Species - metabolism ; Respiration ; Streptozocin ; Ventricular Function, Left</subject><ispartof>Journal of molecular medicine (Berlin, Germany), 2020-02, Vol.98 (2), p.245-261</ispartof><rights>Springer-Verlag GmbH Germany, part of Springer Nature 2020</rights><rights>Journal of Molecular Medicine is a copyright of Springer, (2020). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c441t-abf65452e5c01baa86f6e1f531ac8b3a7770821ac8fce6ef18cbbfc029b61d393</citedby><cites>FETCH-LOGICAL-c441t-abf65452e5c01baa86f6e1f531ac8b3a7770821ac8fce6ef18cbbfc029b61d393</cites><orcidid>0000-0003-1721-0349</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00109-019-01861-2$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00109-019-01861-2$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31897508$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Shawn Yongshun</creatorcontrib><creatorcontrib>Zhu, Siyu</creatorcontrib><creatorcontrib>Wu, Jian</creatorcontrib><creatorcontrib>Zhang, Maomao</creatorcontrib><creatorcontrib>Xu, Yousheng</creatorcontrib><creatorcontrib>Xu, Wei</creatorcontrib><creatorcontrib>Cui, Jinjin</creatorcontrib><creatorcontrib>Yu, Bo</creatorcontrib><creatorcontrib>Cao, Wei</creatorcontrib><creatorcontrib>Liu, Jingjin</creatorcontrib><title>Exercise enhances cardiac function by improving mitochondrial dysfunction and maintaining energy homoeostasis in the development of diabetic cardiomyopathy</title><title>Journal of molecular medicine (Berlin, Germany)</title><addtitle>J Mol Med</addtitle><addtitle>J Mol Med (Berl)</addtitle><description>Diabetic cardiomyopathy (DCM) is a major cause of morbidity and mortality in diabetic patients. Reactive oxygen species (ROS) produced by oxidative stress play an important role in the development of DCM. DCM involves abnormal energy metabolism, thereby reducing energy production. Exercise has been reported to be effective in protecting the heart against ROS accumulation during the development of DCM. We hypothesize that the AMPK/PGC-1α axis may play a crucial role in exercise-induced bioenergetic metabolism and aerobic respiration on oxidative stress parameters in the development of diabetic cardiomyopathy. Using a streptozotocin/high-fat diet mouse to generate a diabetic model, our aim was to evaluate the effects of exercise on the cardiac function, mitochondrial oxidative capacity, mitochondrial function, and cardiac expression of PGC-1α. Mice fed a high-fat diet were given MO-siPGC-1α or treated with AMPK inhibitor. Mitochondrial structure and effects of switching between the Warburg effect and aerobic respiration were analysed. Exercise improved blood pressure and systolic dysfunction in diabetic mouse hearts. The beneficial effects of exercise were also observed in a mitochondrial function study, as reflected by an enhanced oxidative phosphorylation level, increased membrane potential, and decreased ROS level and oxygen consumption. On the other hand, depletion of PGC-1α attenuated the effects of exercise on the enhancement of mitochondrial function. In addition, PGC-1α may be responsible for reversing the Warburg effect to aerobic respiration, thus enhancing mitochondrial metabolism and energy homoeostasis. In this study, we demonstrate the protective effects of exercise on shifting energy metabolism from fatty acid oxidation to glucose oxidation in an established diabetic stage. These data suggest that exercise is effective at ameliorating diabetic cardiomyopathy by improving mitochondrial function and reducing metabolic disturbances.</description><subject>Adenosine Triphosphate - metabolism</subject><subject>Aerobic respiration</subject><subject>AMP-Activated Protein Kinases</subject><subject>Animals</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Blood Pressure</subject><subject>Cardiac function</subject><subject>Cardiomyopathy</subject><subject>Cells, Cultured</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetes Mellitus, Experimental - metabolism</subject><subject>Diabetes Mellitus, Experimental - physiopathology</subject><subject>Diabetes Mellitus, Type 2 - metabolism</subject><subject>Diabetes Mellitus, Type 2 - physiopathology</subject><subject>Diabetic Cardiomyopathies - metabolism</subject><subject>Diabetic Cardiomyopathies - physiopathology</subject><subject>Energy Metabolism</subject><subject>Exercise</subject><subject>Glucose - metabolism</subject><subject>Heart diseases</subject><subject>High fat diet</subject><subject>Homeostasis</subject><subject>Human Genetics</subject><subject>Internal Medicine</subject><subject>Lactic Acid - metabolism</subject><subject>Male</subject><subject>Membrane potential</subject><subject>Membrane Potential, Mitochondrial</subject><subject>Metabolism</subject><subject>Mice, Inbred C57BL</subject><subject>Mitochondria</subject><subject>Mitochondria, Heart - physiology</subject><subject>Molecular Medicine</subject><subject>Morbidity</subject><subject>Myocytes, Cardiac - metabolism</subject><subject>Original Article</subject><subject>Oxidation</subject><subject>Oxidative phosphorylation</subject><subject>Oxidative stress</subject><subject>Oxygen consumption</subject><subject>Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - metabolism</subject><subject>Phosphorylation</subject><subject>Physical Conditioning, Animal</subject><subject>Physical fitness</subject><subject>Reactive oxygen species</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Respiration</subject><subject>Streptozocin</subject><subject>Ventricular Function, Left</subject><issn>0946-2716</issn><issn>1432-1440</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9kc1u1TAQhS1ERS-3fQEWyBIbNqH-i5MsUVWgUiU2sI5sZ3zjKrEvtlORZ-Fl8SWlSF2wGI1G_uYcjw5Cbyj5QAlprhIhlHQVoadqJa3YC7SjgrOKCkFeoh3phKxYQ-U5ep3SfcGbuhOv0DmnbdfUpN2hXzc_IRqXAIMflTeQsFFxcMpgu3iTXfBYr9jNxxgenD_g2eVgxuCH6NSEhzU9YcoPeFbO51InEjzEw4rHMAcIKavkEnYe5xHwAA8wheMMPuNgcbHTkJ3ZrMO8hqPK43qBzqyaElw-9j36_unm2_WX6u7r59vrj3eVEYLmSmkra1EzqA2hWqlWWgnU1pwq02qumqYhLTsN1oAES1ujtTWEdVrSgXd8j95vuuXGHwuk3M8uGZgm5SEsqWecc0matvQ9evcMvQ9L9OV3haoZ75pWyEKxjTIxpBTB9sfoZhXXnpL-FF2_RdeX6Po_0ZXtPXr7KL3oGYanlb9ZFYBvQCpP_gDxn_d_ZH8Dp8OpFA</recordid><startdate>20200201</startdate><enddate>20200201</enddate><creator>Wang, Shawn Yongshun</creator><creator>Zhu, Siyu</creator><creator>Wu, Jian</creator><creator>Zhang, Maomao</creator><creator>Xu, Yousheng</creator><creator>Xu, Wei</creator><creator>Cui, Jinjin</creator><creator>Yu, Bo</creator><creator>Cao, Wei</creator><creator>Liu, Jingjin</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-1721-0349</orcidid></search><sort><creationdate>20200201</creationdate><title>Exercise enhances cardiac function by improving mitochondrial dysfunction and maintaining energy homoeostasis in the development of diabetic cardiomyopathy</title><author>Wang, Shawn Yongshun ; Zhu, Siyu ; Wu, Jian ; Zhang, Maomao ; Xu, Yousheng ; Xu, Wei ; Cui, Jinjin ; Yu, Bo ; Cao, Wei ; Liu, Jingjin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c441t-abf65452e5c01baa86f6e1f531ac8b3a7770821ac8fce6ef18cbbfc029b61d393</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adenosine Triphosphate - metabolism</topic><topic>Aerobic respiration</topic><topic>AMP-Activated Protein Kinases</topic><topic>Animals</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Blood Pressure</topic><topic>Cardiac function</topic><topic>Cardiomyopathy</topic><topic>Cells, Cultured</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetes Mellitus, Experimental - metabolism</topic><topic>Diabetes Mellitus, Experimental - physiopathology</topic><topic>Diabetes Mellitus, Type 2 - metabolism</topic><topic>Diabetes Mellitus, Type 2 - physiopathology</topic><topic>Diabetic Cardiomyopathies - metabolism</topic><topic>Diabetic Cardiomyopathies - physiopathology</topic><topic>Energy Metabolism</topic><topic>Exercise</topic><topic>Glucose - metabolism</topic><topic>Heart diseases</topic><topic>High fat diet</topic><topic>Homeostasis</topic><topic>Human Genetics</topic><topic>Internal Medicine</topic><topic>Lactic Acid - metabolism</topic><topic>Male</topic><topic>Membrane potential</topic><topic>Membrane Potential, Mitochondrial</topic><topic>Metabolism</topic><topic>Mice, Inbred C57BL</topic><topic>Mitochondria</topic><topic>Mitochondria, Heart - 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Academic</collection><jtitle>Journal of molecular medicine (Berlin, Germany)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Shawn Yongshun</au><au>Zhu, Siyu</au><au>Wu, Jian</au><au>Zhang, Maomao</au><au>Xu, Yousheng</au><au>Xu, Wei</au><au>Cui, Jinjin</au><au>Yu, Bo</au><au>Cao, Wei</au><au>Liu, Jingjin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Exercise enhances cardiac function by improving mitochondrial dysfunction and maintaining energy homoeostasis in the development of diabetic cardiomyopathy</atitle><jtitle>Journal of molecular medicine (Berlin, Germany)</jtitle><stitle>J Mol Med</stitle><addtitle>J Mol Med (Berl)</addtitle><date>2020-02-01</date><risdate>2020</risdate><volume>98</volume><issue>2</issue><spage>245</spage><epage>261</epage><pages>245-261</pages><issn>0946-2716</issn><eissn>1432-1440</eissn><abstract>Diabetic cardiomyopathy (DCM) is a major cause of morbidity and mortality in diabetic patients. Reactive oxygen species (ROS) produced by oxidative stress play an important role in the development of DCM. DCM involves abnormal energy metabolism, thereby reducing energy production. Exercise has been reported to be effective in protecting the heart against ROS accumulation during the development of DCM. We hypothesize that the AMPK/PGC-1α axis may play a crucial role in exercise-induced bioenergetic metabolism and aerobic respiration on oxidative stress parameters in the development of diabetic cardiomyopathy. Using a streptozotocin/high-fat diet mouse to generate a diabetic model, our aim was to evaluate the effects of exercise on the cardiac function, mitochondrial oxidative capacity, mitochondrial function, and cardiac expression of PGC-1α. Mice fed a high-fat diet were given MO-siPGC-1α or treated with AMPK inhibitor. Mitochondrial structure and effects of switching between the Warburg effect and aerobic respiration were analysed. Exercise improved blood pressure and systolic dysfunction in diabetic mouse hearts. The beneficial effects of exercise were also observed in a mitochondrial function study, as reflected by an enhanced oxidative phosphorylation level, increased membrane potential, and decreased ROS level and oxygen consumption. On the other hand, depletion of PGC-1α attenuated the effects of exercise on the enhancement of mitochondrial function. In addition, PGC-1α may be responsible for reversing the Warburg effect to aerobic respiration, thus enhancing mitochondrial metabolism and energy homoeostasis. In this study, we demonstrate the protective effects of exercise on shifting energy metabolism from fatty acid oxidation to glucose oxidation in an established diabetic stage. These data suggest that exercise is effective at ameliorating diabetic cardiomyopathy by improving mitochondrial function and reducing metabolic disturbances.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>31897508</pmid><doi>10.1007/s00109-019-01861-2</doi><tpages>17</tpages><orcidid>https://orcid.org/0000-0003-1721-0349</orcidid></addata></record> |
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| ispartof | Journal of molecular medicine (Berlin, Germany), 2020-02, Vol.98 (2), p.245-261 |
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| subjects | Adenosine Triphosphate - metabolism Aerobic respiration AMP-Activated Protein Kinases Animals Biomedical and Life Sciences Biomedicine Blood Pressure Cardiac function Cardiomyopathy Cells, Cultured Diabetes Diabetes mellitus Diabetes Mellitus, Experimental - metabolism Diabetes Mellitus, Experimental - physiopathology Diabetes Mellitus, Type 2 - metabolism Diabetes Mellitus, Type 2 - physiopathology Diabetic Cardiomyopathies - metabolism Diabetic Cardiomyopathies - physiopathology Energy Metabolism Exercise Glucose - metabolism Heart diseases High fat diet Homeostasis Human Genetics Internal Medicine Lactic Acid - metabolism Male Membrane potential Membrane Potential, Mitochondrial Metabolism Mice, Inbred C57BL Mitochondria Mitochondria, Heart - physiology Molecular Medicine Morbidity Myocytes, Cardiac - metabolism Original Article Oxidation Oxidative phosphorylation Oxidative stress Oxygen consumption Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - metabolism Phosphorylation Physical Conditioning, Animal Physical fitness Reactive oxygen species Reactive Oxygen Species - metabolism Respiration Streptozocin Ventricular Function, Left |
| title | Exercise enhances cardiac function by improving mitochondrial dysfunction and maintaining energy homoeostasis in the development of diabetic cardiomyopathy |
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