Cardiovascular diseases are the major cause of morbidity and mortality in obese individuals, particularly in those with an excess accumulation of abdominal visceral fat. Basal cardiac vagal modulation of heart rate is reduced and muscle sympathetic nerve activity (MSNA) is increased in obese individuals. However, recent evidence suggests that abdominal fat may have a more important influence on basal cardiac vagal modulation of heart rate and MSNA than obesity per se. Therefore, the aims of the present proposal are to determine influence of elevated abdominal visceral fat on: 1) basal cardiac vagal modulation of heart rate and MSNA and 2) arterial baroreflex stimulation of cardiac vagal outflow and arterial baroreflex inhibition of MSNA. To address these aims, 120 normotensive non-obese (n=60; BMI less than 25 kg/m2) and obese (n=60; BMI less than 28 less than 35 kg/m2) men and women will be studied. Body composition will be measured by dual energy x-ray absorptiometry and abdominal visceral fat will be quantified using computed tomography. The respiratory sinus arrhythmia (power spectral analysis) will be used to estimate cardiac vagal modulation of heart rate and the microneurographic (peroneal nerve) technique will be used to measure post-ganglionic MSNA under resting conditions. Bolus infusions of nitroprusside and phenylephrine and simultaneously acquired B-mode ultrasound images of the carotid artery dimensions will be used to assess arterial baroreflex control of cardiac vagal outflow and MSNA. Two experimental approaches will be utilized: 1) a cross-sectional comparison of non-obese and obese subjects in the upper and lower 40th percentile for abdominal visceral fat and 2) underfeeding (obese only) to produce a 10 percent decrease in body weight and significant reductions in total body and abdominal visceral fat. All measurements will be performed after a 4-week weight stabilization period where the macronutrient composition and level of sodium intake is standardized. The results of this investigation will provide new physiologically and clinically important information regarding the autonomic-circulatory mechanisms and consequences of an excess accumulation of abdominal visceral fat. This information is crucial considering the growing recognition that autonomic-circulatory dysfunction may be causal factor in a number of cardiovascular (essential hypertension; coronary artery disease) and metabolic (NIDDM) disease states, all of which become more prevalent with increasing levels of body fat, particularly in the abdominal visceral region.
| Davy, Kevin P; Orr, Jeb S (2009) Sympathetic nervous system behavior in human obesity. Neurosci Biobehav Rev 33:116-24 |
| Orr, Jeb S; Gentile, Christopher L; Davy, Brenda M et al. (2008) Large artery stiffening with weight gain in humans: role of visceral fat accumulation. Hypertension 51:1519-24 |
| Gentile, Christopher L; Orr, Jeb S; Davy, Brenda M et al. (2007) Cardiorespiratory fitness influences the blood pressure response to experimental weight gain. Obesity (Silver Spring) 15:3005-12 |
| Alvarez, Guy E; Davy, Brenda M; Ballard, Tasha P et al. (2005) Weight loss increases cardiovagal baroreflex function in obese young and older men. Am J Physiol Endocrinol Metab 289:E665-9 |
| Ho, Richard C; Davy, Kevin P; Hickey, Matthew S et al. (2005) Circulating tumor necrosis factor alpha is higher in non-obese, non-diabetic Mexican Americans compared to non-Hispanic white adults. Cytokine 30:14-21 |
| Davy, Kevin P; Hall, John E (2004) Obesity and hypertension: two epidemics or one? Am J Physiol Regul Integr Comp Physiol 286:R803-13 |
| Alvarez, Guy E; Ballard, Tasha P; Beske, Stacy D et al. (2004) Subcutaneous obesity is not associated with sympathetic neural activation. Am J Physiol Heart Circ Physiol 287:H414-8 |
| Davy, Kevin P (2004) The global epidemic of obesity: are we becoming more sympathetic? Curr Hypertens Rep 6:241-6 |
| Ho, Richard C; Davy, Kevin P; Hickey, Matthew S et al. (2002) Behavioral, metabolic, and molecular correlates of lower insulin sensitivity in Mexican-Americans. Am J Physiol Endocrinol Metab 283:E799-808 |
| Alvarez, Guy E; Beske, Stacy D; Ballard, Tasha P et al. (2002) Sympathetic neural activation in visceral obesity. Circulation 106:2533-6 |
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