This K02 Award proposal requests salary support to protect the applicants time to focus on the proposed studies and associated career development plan. The principal investigator's long-term career goal is to develop a nationally recognized, extramurally funded laboratory focused on determining the mechanisms and consequences of autonomic-circulatory dysfunction in obesity, particularly in those with elevated abdominal visceral fat. Toward this end, the aims of the present proposal are to determine the influence of elevated abdominal visceral fat on: 1) cardiac vagal modulation of heart rate and muscle sympathetic nerve activity (MSNA) in humans; 2) arterial baroreflex stimulation cardiac vagal outflow and inhibition of MSNA, and 3) vascular responsiveness to sympathetic stimulation in humans. The applicant also proposes to obtain preliminary data regarding the influence of DNA sequence variations in specific candidate genes alone and in combination with elevated abdominal visceral fat on autonomic-circulatory phenotypes. The research proposed in this K02 Award will allow the candidate to expand the scope of his current R01 award and enhance his research skills in a number -of areas related to obesity and autonomic-circulatory control in humans namely, 1) to expand the use and application of neurophysiological and vascular imaging techniques; 2) to obtain additional training in the assessment of body composition and regional body fat distribution; and 3) to obtain experience and skills in physiological genomics to study the influence of DNA sequence variations in specific candidate genes on autonomic-circulatory phenotypes alone and in combination with elevated abdominal visceral fat. The protected time and enhancement of research skills provided by this award will equip the candidate to conduct biomedical research well into the future. The results of this investigation will provide new physiologically and clinically important information regarding the contribution of visceral fat and genetics alone and in combination to human variation in autonomic-circulatory control. This information is crucial considering the growing recognition that autonomic dysfunction may be causal factor in a number of CVD states (e.g., essential hypertension) all of which become more prevalent with increasing levels of total body and abdominal visceral fat, particularly in susceptible individuals.
| 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 |
| Gentile, Christopher L; Orr, Jeb S; Davy, Brenda M et al. (2007) Modest weight gain is associated with sympathetic neural activation in nonobese humans. Am J Physiol Regul Integr Comp Physiol 292:R1834-8 |
| Alvarez, Guy E; Halliwill, John R; Ballard, Tasha P et al. (2005) Sympathetic neural regulation in endurance-trained humans: fitness vs. fatness. J Appl Physiol 98:498-502 |
| 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 |
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