Article

Journal of Cardiovascular Translational Research

, Volume 6, Issue 3, pp 436-445

Beneficial Cardiac Effects of Caloric Restriction Are Lost with Age in a Murine Model of Obesity

  • Majd AlGhatrifAffiliated withDivision of Cardiology, Department of Medicine, Johns Hopkins University School of MedicineDivision of Hospital Medicine, Bayview Department of Medicine, Johns Hopkins University School of Medicine
  • , Vabren L. WattsAffiliated withDivision of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine
  • , Xiaolin NiuAffiliated withDivision of Cardiology, Department of Medicine, Johns Hopkins University School of MedicineDepartment of Cardiology, Tangdu Hospital, The Fourth Military Medical University
  • , Marc HalushkaAffiliated withDepartment of Pathology, Johns Hopkins University School of Medicine
  • , Karen L. MillerAffiliated withDivision of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine
  • , Konrad VandegaerAffiliated withDivision of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine
  • , Djahida BedjaAffiliated withDepartment of Comparative Medicine, Johns Hopkins University School of Medicine
  • , Karen Fox-TalbotAffiliated withDepartment of Pathology, Johns Hopkins University School of Medicine
  • , Alicja BielawskaAffiliated withDepartment of Biochemistry and Molecular Biology, Medical University of South Carolina
    • , Kathleen L. GabrielsonAffiliated withDepartment of Comparative Medicine, Johns Hopkins University School of Medicine
    • , Lili A. BarouchAffiliated withDivision of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine Email author 

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Abstract

Obesity is associated with increased diastolic stiffness and myocardial steatosis and dysfunction. The impact of aging on the protective effects of caloric restriction (CR) is not clear. We studied 2-month (younger) and 6–7-month (older)-old ob/ob mice and age-matched C57BL/6J controls (WT). Ob/ob mice were assigned to diet ad libitum or CR for 4 weeks. We performed echocardiograms, myocardial triglyceride assays, Oil Red O staining, and measured free fatty acids, superoxide, NOS activity, ceramide levels, and Western blots. In younger mice, CR restored diastolic function, reversed myocardial steatosis, and upregulated Akt phosphorylation. None of these changes was observed in the older mice; however, CR decreased oxidative stress and normalized NOS activity in these animals. Interestingly, myocardial steatosis was not associated with increased ceramide, but CR altered the composition of ceramides. In this model of obesity, aging attenuates the benefits of CR on myocardial structure and function.

Keywords

Obesity Caloric restriction Steatosis Lipotoxicity Diastolic dysfunction