Beneficial cardiac effects of caloric restriction are lost with age in a murine model of obesity

J Cardiovasc Transl Res. 2013 Jun;6(3):436-45. doi: 10.1007/s12265-013-9453-4. Epub 2013 Mar 2.

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Caloric Restriction*
  • Ceramides / metabolism
  • Diastole
  • Disease Models, Animal
  • Fatty Acids, Nonesterified / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Myocardium / metabolism
  • Myocardium / pathology
  • Nitric Oxide Synthase / metabolism
  • Obesity / complications
  • Obesity / diet therapy*
  • Obesity / metabolism
  • Obesity / physiopathology
  • Oxidative Stress
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism
  • Superoxide Dismutase / metabolism
  • Time Factors
  • Triglycerides / metabolism
  • Ventricular Dysfunction, Left / etiology
  • Ventricular Dysfunction, Left / metabolism
  • Ventricular Dysfunction, Left / physiopathology
  • Ventricular Dysfunction, Left / prevention & control*
  • Ventricular Function, Left
  • Weight Loss

Substances

  • Ceramides
  • Fatty Acids, Nonesterified
  • Triglycerides
  • Nitric Oxide Synthase
  • Superoxide Dismutase
  • Proto-Oncogene Proteins c-akt