Associate Professor of Medicine
Division of Cardiovascular Division
Division of Geriatrics and Gerontology
Washington University School of Medicine
Dr. Peterson has focused her research on human myocardial structure, function, and metabolism in obesity and type 2 diabetes. She has predominantly used multimodality imaging in order to test the hypotheses regarding the pathogenesis of obesity/diabetic cardiomyopathy. She has also published extremely important papers on gender differences in myocardial glucose and oxygen metabolism. Using sophisticated imaging techniques such as positron emission tomography in humans, Dr. Peterson has identified specific physiologic signatures in young obese women that appear to be powerful predictors of abnormal myocardial function (Peterson LR et al. Alterations in left ventricular structure and function in young healthy obese women: Assessment by echocardiography and tissue Doppler imaging. J Am Coll Cardiol, 43:1399-1404, 2004; Peterson LR et al. Effect of obesity and insulin resistance on myocardial substrate metabolism and efficiency in young women. Circulation 109:2191-2196, 2004). She has been elected to the editorial board of the journals Circulation, Progress in Cardiovascular Disease, and Journal of Cardiometabolic Syndrome, and has obtained RO1 funding. Dr. Peterson is currently an Associate Professor of Medicine and Radiology at Washington University School of Medicine.
BIRCWH Scholar from 01/01/2001 until 12/31/2005
Obesity’s Effect on Myocardial Metabolism and its Regulation
Obesity affects more than 43 million Americans and is associated with increased cardiovascular (CV) mortality, and the incidence of obesity has been increasing markedly in women. Upper body obesity (UBO) in particular is associated with major risk factors for CV disease. Obesity causes detrimental structural and functional changes in the heart, e.g., eccentric left ventricular (LV) hypertrophy; however, very little is known about the effect of obesity on myocardial metabolism. In other conditions (e.g., hypertension) associated with similar myocardial structural and functional abnormalities, the myocardium uses less fatty acid and more glucose (a less energy-productive fuel) than normal. Moreover, obesity is associated with decreased skeletal muscle fatty acid oxidation and intracellular fatty acid accumulation. If obesity also causes an accumulation of intracellular fatty acids in the myocardium, it could cause apoptosis and arrythmogenesis, thus directly contributing to an increased risk of CV death. Thus, based on alterations in myocardial substrate metabolism in subjects who have similar myocardial structural and functional changes as those found in obesity and the alterations in skeletal muscle metabolism in obesity, it seems likely that myocardial and total body substrate metabolism at rest will be altered in obese women. Moreover, it seems likely that the regulation of myocardial and total body substrate metabolism (e.g., by insulin) will be altered in obese women, and that these changes in substrate handling may not only be less energy-productive but directly detrimental – potentially increasing the risk of CV death.
Women with UBO will have: 1) decreased myocardial and total body fatty acid and increased glucose metabolism at rest, 2) decreased myocardial sensitivity to insulin-stimulated glucose metabolism, 3) decreased myocardial resting fatty acid metabolism despite increased plasma fatty acid substrate availability, and 4) decreased myocardial sensitivity to catecholamine-stimulated lipolysis and consequent increased plasma fatty acid availability. These characteristics increase the risk of CV death. Thus, our specific aims are to measure A) the effect of UBO in premenopausal women on resting myocardial fatty acid and glucose metabolism and to compare this with total body fatty acid and glucose metabolism, and B) the effect of UBO on the regulation of myocardial fatty acid and glucose metabolism by evaluating metabolism under the following conditions: 1) hyperinsulinemia, 2) increased plasma fatty acid availability, 3) catecholamine-induced increase in plasma fatty acids, and 4) after significant weight loss and under resting conditions.
Our specific aims are to measure: A) the effect of UBO in premenopausal women on resting myocardial fatty acid and glucose metabolism and compare it with total body fatty acid glucose metabolism, and B) the effect of UBO on the regulation of myocardial fatty acid and glucose metabolism by measuring metabolism under the following conditions: 1) during hyperinsulinemia, 2) during an increase in plasma fatty acid availability, 3) during catecholamine-induced increase in plasma fatty acids, and 4) after significant weight loss and under resting conditions.