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

  • Majd AlGhatrif
  • Vabren L. Watts
  • Xiaolin Niu
  • Marc Halushka
  • Karen L. Miller
  • Konrad Vandegaer
  • Djahida Bedja
  • Karen Fox-Talbot
  • Alicja Bielawska
  • Kathleen L. Gabrielson
  • Lili A. Barouch
Article

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 

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Majd AlGhatrif
    • 1
    • 2
  • Vabren L. Watts
    • 1
  • Xiaolin Niu
    • 1
    • 3
  • Marc Halushka
    • 5
  • Karen L. Miller
    • 1
  • Konrad Vandegaer
    • 1
  • Djahida Bedja
    • 4
  • Karen Fox-Talbot
    • 5
  • Alicja Bielawska
    • 6
  • Kathleen L. Gabrielson
    • 4
  • Lili A. Barouch
    • 1
  1. 1.Division of Cardiology, Department of MedicineJohns Hopkins University School of MedicineBaltimoreUSA
  2. 2.Division of Hospital Medicine, Bayview Department of MedicineJohns Hopkins University School of MedicineBaltimoreUSA
  3. 3.Department of Cardiology, Tangdu HospitalThe Fourth Military Medical UniversityXi’anPeople’s Republic of China
  4. 4.Department of Comparative MedicineJohns Hopkins University School of MedicineBaltimoreUSA
  5. 5.Department of PathologyJohns Hopkins University School of MedicineBaltimoreUSA
  6. 6.Department of Biochemistry and Molecular BiologyMedical University of South CarolinaCharlestonUSA

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