Structural and functional characterization of the cardiac mitochondria-associated reticular membranes in the ob/ob mouse model
Type 2 diabetes (T2D) and obesity strongly lead to diabetic cardiomyopathy (DCM). The involvement of mitochondria-associated reticular membranes (MAMs), a signaling hub in the cardiomyocyte, starts to be demonstrated in T2D-related metabolic disorders. We recently discovered a cardiac MAM Ca2+ uncou...
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Elsevier
2025-06-01
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| Series: | Journal of Molecular and Cellular Cardiology Plus |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772976125001722 |
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| author | Hala Guedouari Maya Dia Juliette Geoffray Camille Brun Florentin Moulin Lucas Givre Lucid Belmudes Christelle Leon Stephanie Chanon Jingwei Ji-Cao Christophe Chouabe Sylvie Ducreux Claire Crola Da Silva Ludovic Gomez Yohann Couté Helene Thibault Jennifer Rieusset Melanie Paillard |
| author_facet | Hala Guedouari Maya Dia Juliette Geoffray Camille Brun Florentin Moulin Lucas Givre Lucid Belmudes Christelle Leon Stephanie Chanon Jingwei Ji-Cao Christophe Chouabe Sylvie Ducreux Claire Crola Da Silva Ludovic Gomez Yohann Couté Helene Thibault Jennifer Rieusset Melanie Paillard |
| author_sort | Hala Guedouari |
| collection | DOAJ |
| description | Type 2 diabetes (T2D) and obesity strongly lead to diabetic cardiomyopathy (DCM). The involvement of mitochondria-associated reticular membranes (MAMs), a signaling hub in the cardiomyocyte, starts to be demonstrated in T2D-related metabolic disorders. We recently discovered a cardiac MAM Ca2+ uncoupling in a high-fat high-sucrose diet (HFHSD)-induced mouse model of DCM. To better determine the role of MAMs in the progression of DCM, we here aimed to characterize the proteomic composition and function of the cardiac MAMs of another obesogenic T2D mouse model, the leptin-deficient ob/ob mouse.12-week old male C57Bl6-N ob/ob mice displayed strain rate dysfunction and concentric remodeling, while no change was observed in fractional shortening or diastolic function. Increased lipid deposition but no fibrosis was measured in the ob/ob heart compared to WT. Electron microscopy analysis revealed that cardiac MAM length and width were similar between both groups. A trend towards an increased MAM protein content was measured in the ob/ob heart. MAM proteome analyses showed mainly increased processes in ob/ob hearts: cellular response to stress, lipid metabolism, ion transport and membrane organization. Functionally, MAM-driven Ca2+ fluxes were unchanged but hypoxic stress induced a cell death increase in the ob/ob cardiomyocyte. Mitochondrial respiration, cardiomyocyte shortening, ATP and ROS content were similar between groups.To conclude, at that age, while being strongly hyperglycemic and insulin-resistant, the ob/ob mouse model rather displays a modest DCM without strong changes in MAMs: preserved structural and functional MAM Ca2+ coupling but increased response to stress. |
| format | Article |
| id | doaj-art-d2e6b7eb3fbb4227baead7d3f5bf9a2f |
| institution | DOAJ |
| issn | 2772-9761 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
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| series | Journal of Molecular and Cellular Cardiology Plus |
| spelling | doaj-art-d2e6b7eb3fbb4227baead7d3f5bf9a2f2025-08-20T03:20:01ZengElsevierJournal of Molecular and Cellular Cardiology Plus2772-97612025-06-011210045310.1016/j.jmccpl.2025.100453Structural and functional characterization of the cardiac mitochondria-associated reticular membranes in the ob/ob mouse modelHala Guedouari0Maya Dia1Juliette Geoffray2Camille Brun3Florentin Moulin4Lucas Givre5Lucid Belmudes6Christelle Leon7Stephanie Chanon8Jingwei Ji-Cao9Christophe Chouabe10Sylvie Ducreux11Claire Crola Da Silva12Ludovic Gomez13Yohann Couté14Helene Thibault15Jennifer Rieusset16Melanie Paillard17University Claude Bernard Lyon1, CarMeN Laboratory- IRIS Team, INSERM, INRAE, 69500 Bron, FranceUniversity Claude Bernard Lyon1, CarMeN Laboratory- IRIS Team, INSERM, INRAE, 69500 Bron, France; Laboratory of Experimental and Clinical Pharmacology, Faculty of Sciences, Lebanese University, Beirut, LebanonUniversity Claude Bernard Lyon1, CarMeN Laboratory- IRIS Team, INSERM, INRAE, 69500 Bron, FranceUniversity Claude Bernard Lyon1, CarMeN Laboratory- IRIS Team, INSERM, INRAE, 69500 Bron, FranceUniversity Claude Bernard Lyon1, CarMeN Laboratory- IRIS Team, INSERM, INRAE, 69500 Bron, FranceUniversity Claude Bernard Lyon1, CarMeN Laboratory- IRIS Team, INSERM, INRAE, 69500 Bron, FranceUniv. Grenoble Alpes, INSERM, CEA, UA13 BGE, CNRS, FR2048, 38000 Grenoble, FranceUniversity Claude Bernard Lyon1, CarMeN Laboratory- IRIS Team, INSERM, INRAE, 69500 Bron, FranceUniversity Claude Bernard Lyon1, CarMeN Laboratory– MERISM team, INSERM, INRAE, 69921 Oullins, FranceUniversity Claude Bernard Lyon1, CarMeN Laboratory– MERISM team, INSERM, INRAE, 69921 Oullins, FranceUniversity Claude Bernard Lyon1, CarMeN Laboratory- IRIS Team, INSERM, INRAE, 69500 Bron, FranceUniversity Claude Bernard Lyon1, CarMeN Laboratory- IRIS Team, INSERM, INRAE, 69500 Bron, FranceUniversity Claude Bernard Lyon1, CarMeN Laboratory- IRIS Team, INSERM, INRAE, 69500 Bron, FranceUniversity Claude Bernard Lyon1, CarMeN Laboratory- IRIS Team, INSERM, INRAE, 69500 Bron, FranceUniv. Grenoble Alpes, INSERM, CEA, UA13 BGE, CNRS, FR2048, 38000 Grenoble, FranceUniversity Claude Bernard Lyon1, CarMeN Laboratory- IRIS Team, INSERM, INRAE, 69500 Bron, France; Hospices Civils de Lyon, 69500 Bron, FranceUniversity Claude Bernard Lyon1, CarMeN Laboratory– MERISM team, INSERM, INRAE, 69921 Oullins, FranceUniversity Claude Bernard Lyon1, CarMeN Laboratory- IRIS Team, INSERM, INRAE, 69500 Bron, France; Corresponding author at: Laboratoire CARMEN, Groupement Hospitalier Est, Bâtiment B13, 59 boulevard Pinel, 69500 Bron, France.Type 2 diabetes (T2D) and obesity strongly lead to diabetic cardiomyopathy (DCM). The involvement of mitochondria-associated reticular membranes (MAMs), a signaling hub in the cardiomyocyte, starts to be demonstrated in T2D-related metabolic disorders. We recently discovered a cardiac MAM Ca2+ uncoupling in a high-fat high-sucrose diet (HFHSD)-induced mouse model of DCM. To better determine the role of MAMs in the progression of DCM, we here aimed to characterize the proteomic composition and function of the cardiac MAMs of another obesogenic T2D mouse model, the leptin-deficient ob/ob mouse.12-week old male C57Bl6-N ob/ob mice displayed strain rate dysfunction and concentric remodeling, while no change was observed in fractional shortening or diastolic function. Increased lipid deposition but no fibrosis was measured in the ob/ob heart compared to WT. Electron microscopy analysis revealed that cardiac MAM length and width were similar between both groups. A trend towards an increased MAM protein content was measured in the ob/ob heart. MAM proteome analyses showed mainly increased processes in ob/ob hearts: cellular response to stress, lipid metabolism, ion transport and membrane organization. Functionally, MAM-driven Ca2+ fluxes were unchanged but hypoxic stress induced a cell death increase in the ob/ob cardiomyocyte. Mitochondrial respiration, cardiomyocyte shortening, ATP and ROS content were similar between groups.To conclude, at that age, while being strongly hyperglycemic and insulin-resistant, the ob/ob mouse model rather displays a modest DCM without strong changes in MAMs: preserved structural and functional MAM Ca2+ coupling but increased response to stress.http://www.sciencedirect.com/science/article/pii/S2772976125001722SR-mitochondria couplingMERCsDatabaseDiabetic cardiopathyMitochondrial calcium uniporterERMCs |
| spellingShingle | Hala Guedouari Maya Dia Juliette Geoffray Camille Brun Florentin Moulin Lucas Givre Lucid Belmudes Christelle Leon Stephanie Chanon Jingwei Ji-Cao Christophe Chouabe Sylvie Ducreux Claire Crola Da Silva Ludovic Gomez Yohann Couté Helene Thibault Jennifer Rieusset Melanie Paillard Structural and functional characterization of the cardiac mitochondria-associated reticular membranes in the ob/ob mouse model Journal of Molecular and Cellular Cardiology Plus SR-mitochondria coupling MERCs Database Diabetic cardiopathy Mitochondrial calcium uniporter ERMCs |
| title | Structural and functional characterization of the cardiac mitochondria-associated reticular membranes in the ob/ob mouse model |
| title_full | Structural and functional characterization of the cardiac mitochondria-associated reticular membranes in the ob/ob mouse model |
| title_fullStr | Structural and functional characterization of the cardiac mitochondria-associated reticular membranes in the ob/ob mouse model |
| title_full_unstemmed | Structural and functional characterization of the cardiac mitochondria-associated reticular membranes in the ob/ob mouse model |
| title_short | Structural and functional characterization of the cardiac mitochondria-associated reticular membranes in the ob/ob mouse model |
| title_sort | structural and functional characterization of the cardiac mitochondria associated reticular membranes in the ob ob mouse model |
| topic | SR-mitochondria coupling MERCs Database Diabetic cardiopathy Mitochondrial calcium uniporter ERMCs |
| url | http://www.sciencedirect.com/science/article/pii/S2772976125001722 |
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