ABDOMINAL FAT AND AUTONOMIC CIRCULATORY CONTROL IN HUMAN

心血管疾病是肥胖个体发病和死亡的主要原因，特别是在那些腹部内脏脂肪过度积累的个体中。 在肥胖个体中，心率的基础心脏迷走神经调节减少，肌肉交感神经活动（MSNA）增加。然而，最近的证据表明，腹部脂肪可能比肥胖本身对心率和MSNA的基础心脏迷走神经调制有更重要的影响。 因此，本提案的目的是确定腹部内脏脂肪升高对以下方面的影响：1）心率和MSNA的基础心脏迷走神经调制，以及2）心脏迷走神经流出的动脉压力反射刺激和MSNA的动脉压力反射抑制。为了实现这些目标，将研究120名血压正常的非肥胖（n=60; BMI小于25 kg/m2）和肥胖（n=60; BMI小于28小于35 kg/m2）男性和女性。 将通过双能X线吸收测定法测量身体组成，并使用计算机断层扫描对腹部内脏脂肪进行定量。 呼吸性窦性心律失常（功率谱分析）将用于估计心率的心脏迷走神经调制，显微神经摄影（腓神经）技术将用于测量静息状态下的节后MSNA。 将使用硝普钠和苯肾上腺素的推注以及同时采集的颈动脉尺寸的B型超声图像来评估心脏迷走神经流出和MSNA的动脉压力反射控制。 将使用两种实验方法：1）在腹部内脏脂肪的上和下第40百分位数中对非肥胖和肥胖受试者进行横断面比较，2）喂养不足（仅肥胖），以使体重降低10%，全身和腹部内脏脂肪显著减少。 所有测量将在4周体重稳定期后进行，其中大量营养素组成和钠摄入水平标准化。 这项研究的结果将提供新的生理和临床上重要的信息有关的血液循环机制和后果的过度积累腹部内脏脂肪。 这一信息是至关重要的，因为越来越多的人认识到，血液循环功能障碍可能是许多心血管（原发性高血压;冠状动脉疾病）和代谢（NIDDM）疾病状态的致病因素，所有这些疾病都随着体脂水平的增加而变得更加普遍，特别是在腹部内脏区域。

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.