Effect of Obesity and Insulin Resistance on Myocardial Substrate Metabolism and Efficiency in Young Women

Abstract

Background-Obesity is a risk factor for impaired cardiac performance, particularly in women. Animal studies suggest that alterations in myocardial fatty acid metabolism and efficiency in obesity can cause decreased cardiac performance.In the present study, we tested the hypothesis that myocardial fatty acid metabolism and efficiency are abnormal in obese women. (rϭ0.58, PϽ0.005). A multivariate, stepwise regression analysis showed that BMI was the only independent predictor of MV O 2 and efficiency (Pϭ0.0005 and PϽ0.05, respectively). Glucose AUC was the only independent predictor of MFAUp, MFAU, and MFAO (PϽ0.05, Ͻ0.005, and Ͻ0.005, respectively). Conclusions-In young women, obesity is a significant predictor of increased MV O 2 and decreased efficiency, and insulin resistance is a robust predictor of MFAUp, MFAU, and MFAO. This increase in fatty acid metabolism and decrease in efficiency is concordant with observations made in experimental models of obesity. These metabolic changes may play a role in the pathogenesis of decreased cardiac performance in obese women.

Cardiovascular consequences of obesity and targets for treatment

“…In a study of young women with uncomplicated obesity, our group found that myocardial FA upake, utilization, and oxidation all were increased as BMI and whole body insulin resistance increased, paralleling what was found in animal models of obesity [56,58]. It appears that this increased FA oxidation capacity in humans may also be overwhelmed, as it can be in animal models because autopsy and magnetic resonance spectroscopy studies both demonstrate that in subjects with diabetes there is an increase in intramyocellular triglyceride compared with normal controls [59].…”

“…Lastly, increasing BMI is an independent predictor of increasing myocardial oxygen consumption and decreasing efficiency both in animal models and in a recent study in young obese women [58,66]. Decreased efficiency may contribute to impaired ATP production, thereby hindering cardiac function, and decreased efficiency is a hallmark of heart failure.…”

Relationship between preclinical abnormalities of global and regional left ventricular function and insulin resistance in severe obesity: a Color Doppler Imaging Study

“…5,6 Some recent observations by positron emission tomography showed that in obese young women, insulin resistance and obesity are strictly related to alterations of fatty acid metabolism (uptake, utilization and oxidation), which could play a role in a decreased cardiac performance. 7 Indeed, long-standing obesity can induce left ventricular structural and functional abnormalities, characterized by volume overload and hyperdynamism, eccentric left ventricular hypertrophy, diastolic dysfunction and, occasionally, systolic dysfunction and heart failure. 8 Pulsed-Wave Tissue Doppler Imaging (PW-TDI) of the mitral annulus has demonstrated the capability to a relatively load-independent analysis of the global longitudinal myocardial 9,10 Color-Doppler Myocardial Imaging (CDMI) echocardiography-derived strain rate (SR) and strain measurements are new quantitative indices of regional intrinsic myocardial deformation.…”

Comparative study of rate pressure product in obese women with non obese women.

“…The increase in MVO 2 associated with an increase in BMI is likely related to the effect of obesity on cardiac remodeling and the fact that obesity increases sympathetic tone, preload and fatty acid metabolism. Increased fatty acid uptake and oxidation by the heart can also increase MVO 2 , because more oxygen is required to generate ATP from fatty acid than by glucose metabolism 5 . In agreement with our study, Linda R. Peterson et al demonstrated in young women, obesity is a sign ificant predictor of increased MVO 2 and decreased cardiac efficiency 5 .…”

“…But the data from animal studies suggest that obesity increases myocardial fatty acid metabolism & oxygen consumption leading to increased oxidative stress, cardiac dysfunction & apoptosis 5 . We limited our study population to women because obesity is more common in women than in men and the relative risk of heart failure is greater in obese women than in obese men 5 . Women gain weights mostly between ages of 35 -45 yrs of age.…”