title: High-fat diet induces metabolic changes and reduces oxidative stress in female mouse hearts.
abstract: After an acute myocardial infarction, obese patients generally have a better prognosis than their leaner counterparts, known as the "obesity paradox". In addition, female sex is associated with a lower risk of cardiac ischemic events and smaller infarct size compared to males. The objective of the present work was to study the metabolic phenotype and mitochondrial function associated to female sex and short-term high-fat diet.1H NMR spectra of mice heart extracts were analysed by mRMR variable selection and linear discriminant analysis was used to evaluate metabolic changes. In separate experiments, O2consumption and H2O2production were measured from isolated mitochondria as well as serum oxidation susceptibility. Fingerprinting showed that male hearts contained more myo-inositol, taurine and glutamate than female hearts. HFD reduced the levels of creatine, taurine citrate and acetate. Profiling showed increased alanine and fumarate in HFD suggesting altered glycolitic and Krebs cycle pathways. Female mice contained less glucose than males. Female sex nor HFD altered mitochondria oxygen consumption but both conditions reduced the amount of H2O2produced in an additive manner. Serum of females had lower oxidation susceptibility than serum from males but there were no differences associated with HFD. In conclusion, female sex and short-term HFD have an effect on the myocardial metabolic pattern and reduce the amount of H2O2produced by mitochondria in an additive manner suggesting different mechanisms of action. This could explain, at least in part, the protection afforded by female sex and the "obesity paradox".
authors.affiliation: Laboratorio de Enfermedades Cardiovasculares, Servicio de Cardiología, Hospital Universitari Vall d'Hebron and Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain. Electronic address: ignasi.barba@vhir.org.
authors.forename: Ignasi
authors.initials: I
authors.lastname: Barba
authors.affiliation: Laboratorio de Enfermedades Cardiovasculares, Servicio de Cardiología, Hospital Universitari Vall d'Hebron and Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Miró-Casas
authors.affiliation: Departamento de Matemáticas, Facultad de Ciencias, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: José L
authors.initials: JL
authors.lastname: Torrecilla
authors.affiliation: Laboratorio de Enfermedades Cardiovasculares, Servicio de Cardiología, Hospital Universitari Vall d'Hebron and Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Eulàlia
authors.initials: E
authors.lastname: Pladevall
authors.affiliation: Laboratorio de Enfermedades Cardiovasculares, Servicio de Cardiología, Hospital Universitari Vall d'Hebron and Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Sergi
authors.initials: S
authors.lastname: Tejedor
authors.affiliation: Laboratorio de Enfermedades Cardiovasculares, Servicio de Cardiología, Hospital Universitari Vall d'Hebron and Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Rubén
authors.initials: R
authors.lastname: Sebastián-Pérez
authors.affiliation: Laboratorio de Enfermedades Cardiovasculares, Servicio de Cardiología, Hospital Universitari Vall d'Hebron and Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Marisol
authors.initials: M
authors.lastname: Ruiz-Meana
authors.affiliation: Departamento de Matemáticas, Facultad de Ciencias, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: José R
authors.initials: JR
authors.lastname: Berrendero
authors.affiliation: Departamento de Matemáticas, Facultad de Ciencias, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cuevas
authors.affiliation: Laboratorio de Enfermedades Cardiovasculares, Servicio de Cardiología, Hospital Universitari Vall d'Hebron and Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: García-Dorado
mesh_terms: D000818:Animals; D001835:Body Weight; D059305:Diet, High-Fat / Q000009:adverse effects*; D005260:Female; D006861:Hydrogen Peroxide / Q000378:metabolism; D008055:Lipids / Q000097:blood; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055432:Metabolomics / Q000379:methods; D008810:Mice, Inbred C57BL; D008929:Mitochondria, Heart / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D010101:Oxygen Consumption; D012737:Sex Factors
chemical_list: D008055:Lipids; D006861:Hydrogen Peroxide
keywords: Antioxidant capacity; Gender differences; Metabolomics; Mitochondrial function; Myocardial metabolism; NMR; Obesity