Adipose tissue mitochondrial dysfunction promotes obesity cardiomyopathy

Rafael Romero-Becerra1, Ana Belén Alonso-Aguado2, Alba C. Arcones2, Juan Antonio Lopez1,3, Alfonso Mora2, Alessia Ferrarini1, Estefanía Nuñez1, Ivana Nikolic1, Luis Leiva-Vega2, Maria Elena Rodríguez2, Marta León2, Nuria Matesanz1, Jorge-Luis Torres4,5, Lourdes Hernández-Cosido6,7, Juan Carlos Silla-Castro1, Francisco González-Romero8, Patricia Aspichueta8,9, Fátima Sanchez-Cabo1, Miguel Marcos6,7, Valentín Fuster1, Jesús Vázquez1,3 y Guadalupe Sabio2

1. Centro Nacional de Investigaciones Cardivasculares (CNIC), Madrid, Spain
2. Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain
3. CIBER de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain
4. University Hospital of Salamanca-SACYL-IBSAL, Salamanca, Spain
5. Complejo Asistencial de Zamora-SACYL, Zamora, Spain
6. University Hospital of Salamanca, Salamanca, Spain
7. University of Salamanca, Salamanca, Spain
8. Faculty of Medicine and Nursing, University of Basque Country UPV/EHU, Leioa, Spain
9. BioCruces Bizkaia Health Research Institute, Cruces University Hospital, CIBERehd, Barakaldo, Spain

Obesity, a condition resulting from an excess of adipose tissue, is a serious health problem worldwide and an important factor in the development and progression of cardiovascular diseases. It is well established that mitochondrial dysfunction in adipose tissue might contribute to obesity-related diseases. We found that adipose tissue of obese patients showed a reduced expression of PGC1α, an important mitochondrial regulator. High-fat diet feeding in mice also promoted a downregulation in PGC1α expression in adipose tissue that was accompanied by cardiac metabolism alteration. Echocardiographic analysis of mice lacking PGC1α specifically in adipose tissue showed that these mice develop a cardiac dysfunction like the one observed during obesity. However, this cardiomyopathy was not accompanied by diabetes, hypertension or increased adiposity. Proteomics analysis of plasma from these mice and obese participants from a second human cohort revealed several promising adipokines that could be involved in obesity cardiomyopathy.

Rafael Romero-Becerra (FPU17/03847) and Ana Belén Alonso-Aguado (FPU22/01698), received funding from Programa de Formación del Profesorado Universitario. Guadalupe Sabio is a EMBO YIP member, received funding from the following programmes and organizations: MICIN-FEDERPID2022-138525OB-I002023-26 funded by MICIU/AEI/10.13039/501100011033 and ERDF/UE; Infraestructura de Medicina de Precisión asociada a la Ciencia y Tecnología IMPACT-2021. Instituto de Salud Carlos III., PDC2021-121147-I00.Convocatoria: Proyectos Prueba de Concepto 2021. Ministerio de Ciencia e Innovación.