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Beneficial Cardiac Effects of Caloric Restriction Are Lost with Age in a Murine Model of Obesity |
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| Authors: | 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 |
| Affiliation: | 1. Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Carnegie 568, Baltimore, MD, 21287, USA 2. Division of Hospital Medicine, Bayview Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA 3. Department of Cardiology, Tangdu Hospital, The Fourth Military Medical University, Xi’an, People’s Republic of China 5. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA 4. Department of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA 6. Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, USA |
| 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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