title: Mild and Short-Term Caloric Restriction Prevents Obesity-Induced Cardiomyopathy in Young Zucker Rats without Changing in Metabolites and Fatty Acids Cardiac Profile.
abstract: Caloric restriction (CR) ameliorates cardiac dysfunction associated with obesity. However, most of the studies have been performed under severe CR (30-65% caloric intake decrease) for several months or even years in aged animals. Here, we investigated whether mild (20% food intake reduction) and short-term (2-weeks) CR prevented the obese cardiomyopathy phenotype and improved the metabolic profile of young (14 weeks of age) genetically obese Zuckerfa/farats. Heart weight (HW) and HW/tibia length ratio was significantly lower infa/farats after 2 weeks of CR than in counterparts fedad libitum. Invasive pressure measurements showed that systolic blood pressure, maximal rate of positive left ventricle (LV) pressure, LV systolic pressure and LV end-diastolic pressure were all significantly higher in obesefa/farats than inleancounterparts, which were prevented by CR. Magnetic resonance imaging revealed that the increase in LV end-systolic volume, stroke volume and LV wall thickness observed infa/farats was significantly lower in animals on CR diet. Histological analysis also revealed that CR blocked the significant increase in cardiomyocyte diameter in obesefa/farats. High resolution magic angle spinning magnetic resonance spectroscopy analysis of the LV revealed a global decrease in metabolites such as taurine, creatine and phosphocreatine, glutamate, glutamine and glutathione, in obesefa/farats, whereas lactate concentration was increased. By contrast, fatty acid concentrations in LV tissue were significantly elevated in obesefa/farats. CR failed to restore the LV metabolomic profile of obesefa/farats. In conclusion, mild and short-term CR prevented an obesity-induced cardiomyopathy phenotype in young obesefa/farats independently of the cardiac metabolic profile.
authors.affiliation: Unidad de Hipertensión, Instituto de Investigación Imas12, Hospital Universitario 12 de OctubreMadrid, Spain; Facultad de Farmacia, Instituto Pluridisciplinar, Universidad Complutense de MadridMadrid, Spain.
authors.forename: Gema
authors.initials: G
authors.lastname: Ruiz-Hurtado
authors.affiliation: Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad CEU-San Pablo Madrid, Spain.
authors.forename: Concha F
authors.initials: CF
authors.lastname: García-Prieto
authors.affiliation: Unidad de Hipertensión, Instituto de Investigación Imas12, Hospital Universitario 12 de OctubreMadrid, Spain; Facultad de Farmacia, Instituto Pluridisciplinar, Universidad Complutense de MadridMadrid, Spain.
authors.forename: Helena
authors.initials: H
authors.lastname: Pulido-Olmo
authors.affiliation: Departamento de Anatomía, Histología y Neurociencia, Facultad de Medicina. Universidad Autónoma de Madrid Madrid, Spain.
authors.forename: Juan P
authors.initials: JP
authors.lastname: Velasco-Martín
authors.affiliation: CAI de RMN y RSE, Facultad de Químicas, Universidad Complutense Madrid, Spain.
authors.forename: Palmira
authors.initials: P
authors.lastname: Villa-Valverde
authors.affiliation: CAI de RMN y RSE, Facultad de Químicas, Universidad Complutense Madrid, Spain.
authors.forename: María E
authors.initials: ME
authors.lastname: Fernández-Valle
authors.affiliation: Departamento de Metabolismo y Señalización Celular, Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM) Madrid, Spain.
authors.forename: Lisardo
authors.initials: L
authors.lastname: Boscá
authors.affiliation: Departamento de Metabolismo y Señalización Celular, Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM)Madrid, Spain; Departamento de Metabolismo y Señalización Celular, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ)Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Fernández-Velasco
authors.affiliation: Departamento de Anatomía, Histología y Neurociencia, Facultad de Medicina. Universidad Autónoma de Madrid Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Regadera
authors.affiliation: Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad CEU-San Pablo Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Somoza
authors.affiliation: Facultad de Farmacia, Instituto Pluridisciplinar, Universidad Complutense de Madrid Madrid, Spain.
authors.forename: María S
authors.initials: MS
authors.lastname: Fernández-Alfonso
keywords: caloric restriction; hypertension; hypertrophy; metabolite profile; nuclear magnetic resonance; obesity-induced cardiomyopathy