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

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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.

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Funding

The authors are grateful for the financial support of the American Heart Association Beginning Grant-In-Aid [to L.A.B.], American Diabetes Association [to L.A.B.], and the National Institutes of Health [5T32HL007227 to V.L.W]. There are no relationships to disclose.

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Authors and Affiliations

  1. Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Carnegie 568, Baltimore, MD, 21287, USA

    Majd AlGhatrif, Vabren L. Watts, Xiaolin Niu, Karen L. Miller, Konrad Vandegaer & Lili A. Barouch

  2. Division of Hospital Medicine, Bayview Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Majd AlGhatrif

  3. Department of Cardiology, Tangdu Hospital, The Fourth Military Medical University, Xi’an, People’s Republic of China

    Xiaolin Niu

  4. Department of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Djahida Bedja & Kathleen L. Gabrielson

  5. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Marc Halushka & Karen Fox-Talbot

  6. Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, USA

    Alicja Bielawska

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  1. Majd AlGhatrif
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Correspondence to Lili A. Barouch.

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AlGhatrif, M., Watts, V.L., Niu, X. et al. Beneficial Cardiac Effects of Caloric Restriction Are Lost with Age in a Murine Model of Obesity. J. of Cardiovasc. Trans. Res. 6, 436–445 (2013). https://doi.org/10.1007/s12265-013-9453-4

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  • DOI: https://doi.org/10.1007/s12265-013-9453-4

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