Abstract 159: Beneficial Cardiac Effects of Caloric Restriction in a Murine Model of Obesity Are Attenuated with Age
Introduction: Obesity is associated with increased myocardial steatosis, cardiac dysfunction, mitochondrial uncoupling, and increased apoptosis. Caloric restriction (CR) in older leptin deficient ob/obobese micefails to reduce cardiac steatosis and apoptosis but improves mitochondrial function. This discordant response to caloric restriction and the role of aging in this process are not well understood.
Methods: We studied 4 month (younger) and 8 month (older) old ob/ob mice and age matched C57BL/6J controls. In each age group, ob/ob mice were assigned to ad lib (AL-ob) or calorie restriction (CR-ob) for 4 weeks. We performed echocardiograms, myocardial triglyceride assays, Oil Red O staining, LC-MS/MS ceramide species measurements, and Western blots. Whole animal metabolism was measured using indirect calorimetry.
Results: In younger mice, CR reversed the adverse cardiac effects of obesity by reducing heart weight and ventricular wall thickness, reversing myocardial steatosis measured by myocardial TG assay and Oil red O staining, and upregulating phosphorylation of Akt. This was associated with improvement in diastolic function demonstrated by reduction in isovolumetric relaxation time by echocardiography. In contrast, none of these beneficial changes were observed in the older mice. Whole animal metabolism showed that younger CR-ob mice had decreased respiratory exchange ratio compared to AL-ob, indicating greater reliance on fat as a source of energy. Interestingly, the effect of CR on lipotoxicity measured by the composition of ceramides was similar in both age groups.
Conclusion: In this model of obesity, aging attenuates the benefits of CR on myocardial structure and function. This may be due to older animals’ decreased ability to reverse myocardial steatosis and/or accumulation of oxidative damage over time, and the loss of Akt activation with age.
- © 2012 by American Heart Association, Inc.