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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)436-445
Number of pages10
JournalJournal of Cardiovascular Translational Research
Volume6
Issue number3
DOIs
Publication statusPublished - Jun 2013
Externally publishedYes

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