- Background: Obesity is a risk factor for diseases including type 2 diabetes mellitus (T2DM) and cardiovascular disorders. Diabetes itself contributes to cardiac damage. Thus, studying cardiovascular events and establishing therapeutic intervention in the period of type T2DM onset and manifestation are of highest importance. Mitochondrial dysfunction is one of the pathophysiological mechanisms leading to impaired cardiac function. Methods: An adequate animal model for studying pathophysiology of T2DM is the New Zealand Obese (NZO) mouse. These mice were maintained on a high-fat diet (HFD) without carbohydrates for 13 weeks followed by 4 week HFD with carbohydrates. NZO mice developed severe obesity and only male mice developed manifest T2DM. We determined cardiac phenotypes and mitochondrial function as well as cardiomyocyte signaling in this model. Results: The development of an obese phenotype and T2DM in male mice was accompanied by an impaired systolic function as judged by echocardiography and MyH6/7 expression. Moreover, theBackground: Obesity is a risk factor for diseases including type 2 diabetes mellitus (T2DM) and cardiovascular disorders. Diabetes itself contributes to cardiac damage. Thus, studying cardiovascular events and establishing therapeutic intervention in the period of type T2DM onset and manifestation are of highest importance. Mitochondrial dysfunction is one of the pathophysiological mechanisms leading to impaired cardiac function. Methods: An adequate animal model for studying pathophysiology of T2DM is the New Zealand Obese (NZO) mouse. These mice were maintained on a high-fat diet (HFD) without carbohydrates for 13 weeks followed by 4 week HFD with carbohydrates. NZO mice developed severe obesity and only male mice developed manifest T2DM. We determined cardiac phenotypes and mitochondrial function as well as cardiomyocyte signaling in this model. Results: The development of an obese phenotype and T2DM in male mice was accompanied by an impaired systolic function as judged by echocardiography and MyH6/7 expression. Moreover, the mitochondrial function only in male NZO hearts was significantly reduced and ERK1/2 and AMPK protein levels were altered. Conclusions: This is the first report demonstrating that the cardiac phenotype in male diabetic NZO mice is associated with impaired cardiac energy function and signaling events.…
MetadatenAuthor details: | Cathleen JohnORCiD, Jana Grune, Christiane Ott, Kerstin NowotnyGND, Stefanie Deubel, Arne Kühne, Carola Schubert, Ulrich KintscherORCiD, Vera Regitz-ZagrosekORCiDGND, Tilman GruneORCiDGND |
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DOI: | https://doi.org/10.3389/fendo.2018.00732 |
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ISSN: | 1664-2392 |
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Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/30564194 |
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Title of parent work (English): | Frontiers in Endocrinology |
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Publisher: | Frontiers Research Foundation |
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Place of publishing: | Lausanne |
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Publication type: | Article |
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Language: | English |
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Date of first publication: | 2018/12/04 |
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Publication year: | 2018 |
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Release date: | 2020/12/15 |
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Tag: | NZO; echocardiography; heart; mitochondrial function; obesity; systolic function |
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Volume: | 9 |
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Number of pages: | 9 |
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Funding institution: | Federal Ministry of Education & Research (BMBF), State of Brandenburg (DZD grant), DZHK, Margarete-Ammon Stiftung, Gesundheitscampus Brandenburg |
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Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Ernährungswissenschaft |
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DDC classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Peer review: | Referiert |
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Publishing method: | Open Access / Gold Open-Access |
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| DOAJ gelistet |
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License (German): | CC-BY - Namensnennung 4.0 International |
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