Obesity is a major public health problem affecting over one third of adults in the United States and one in five children. Obesity is related to an increased risk of cardiovascular mortality, which may in part be mediated through a direct effect on the heart leading to dysfunction. However, the time course over which obesity leads to cardiac dysfuncfion, the underlying mechanisms of myocardial dysfunction in obesity, and potential treatments have not been fully elucidated. Our preliminary data ufilizing cardiac magnefic resonance imaging (MRI) show abnormalifies in the magnitude of contracfion, synchrony of contraction, and myocardial mass in the hearts of mice fed a high-fat Western diet. The objective of this project is to define the time course over which this dysfunction occurs in mice, evaluate the role of hypertension in the development of this dysfunction, and to translate this work into humans by determining whether children in our pediatric obesity clinic have evidence of cardiac dysfunction. This project has 3 specific aims as follows: 1) Determine the time course over which myocardial dysfunction develops in mice fed a high-fat Western diet. We will quantify advanced measures of cardiac function assessing mass, contraction and relaxation and synchrony overtime in a longitudinal study using magnetic resonance imaging. 2) Determine the effect of anti-hypertensive therapy on the development of hypertrophy and cardiac dysfunction in mice fed a high-fat Western diet. Mice on a high-fat Western diet develop obesity-related hypertension that is reversible with anti-hypertensive therapy. However, the effect of anti-hypertensive therapy on cardiac function in obese mice has not been studied and may elucidate underiying mechanisms. We will compare cardiac function measured in the'mice on a high-fat Western diet in specific aim 1 to a group of mice on a high-fat Western diet and hydralazine. 3) Quantify cardiac function in children with obesity using advanced MRI. State-of-the-art technology at the University of Kentucky enables us to directly translate our findings in mice into our pediatric obesity clinic with over 800 patients. The effect of obesity on myocardial function in children is largely unknown.
Obesity affects over one third of adults in the United States and one in five children. The objective of this project is to understand the effects of obesity on the function of the heart using advanced magnetic resonance imaging (MRI) of the hearts of both mice and humans. Part of this project will also investigate the specific role of blood pressure medications on helping to protect the heart from the effects of obesity.
|Murphy, Margaret O; Petriello, Michael C; Han, Sung Gu et al. (2016) Exercise protects against PCB-induced inflammation and associated cardiovascular risk factors. Environ Sci Pollut Res Int 23:2201-11|
|Lolay, Georges A; Abdel-Latif, Ahmed K (2016) Trauma induced myocardial infarction. Int J Cardiol 203:19-21|
|Park, Se-Hyung; Liu, Zun; Sui, Yipeng et al. (2016) IKKÎ² Is Essential for Adipocyte Survival and Adaptive Adipose Remodeling in Obesity. Diabetes 65:1616-29|
|Adamiak, M; Poniewierska-Baran, A; Borkowska, S et al. (2016) Evidence that a lipolytic enzyme-hematopoietic-specific phospholipase C-Î²2-promotes mobilization of hematopoietic stem cells by decreasing their lipid raft-mediated bone marrow retention and increasing the promobilizing effects of granulocytes. Leukemia 30:919-28|
|Pumphrey, Ashley; Yang, Zhengshi; Ye, Shaojing et al. (2016) Advanced cardiac chemical exchange saturation transfer (cardioCEST) MRI for in vivo cell tracking and metabolic imaging. NMR Biomed 29:74-83|
|Platt, Kristen M; Charnigo, Richard J; Shertzer, Howard G et al. (2016) Branched-Chain Amino Acid Supplementation in Combination with Voluntary Running Improves Body Composition in Female C57BL/6 Mice. J Diet Suppl 13:473-86|
|Wu, Chia-Hua; Mohammadmoradi, Shayan; Thompson, Joel et al. (2016) Adipocyte (Pro)Renin-Receptor Deficiency Induces Lipodystrophy, Liver Steatosis and Increases Blood Pressure in Male Mice. Hypertension 68:213-9|
|Howatt, Deborah A; Balakrishnan, Anju; Moorleghen, Jessica J et al. (2016) Leukocyte Calpain Deficiency Reduces Angiotensin II-Induced Inflammation and Atherosclerosis But Not Abdominal Aortic Aneurysms in Mice. Arterioscler Thromb Vasc Biol 36:835-45|
|Li, Jing; Song, Jun; Zaytseva, Yekaterina Y et al. (2016) An obligatory role for neurotensin in high-fat-diet-induced obesity. Nature 533:411-5|
|Hamlet, Sean M; Haggerty, Christopher M; Suever, Jonathan D et al. (2016) Optimal configuration of respiratory navigator gating for the quantification of left ventricular strain using spiral cine displacement encoding with stimulated echoes (DENSE) MRI. J Magn Reson Imaging :|
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