ABDOMINAL FAT AND AUTONOMIC CIRCULATORY CONTROL IN HUMAN

心血管疾病是肥胖者发病和死亡的主要原因，特别是在腹部内脏脂肪过度积聚的人中。肥胖者基础心脏迷走神经对心率的调制减少，肌交感神经活动(MSNA)增加。然而，最近的证据表明，腹部脂肪对基础心脏迷走调制心率和MSNA的影响可能比肥胖本身更重要。因此，本研究的目的是确定腹内脂肪升高对：1)基础心脏迷走神经调节心率和MSNA的影响；2)动脉压力反射刺激心脏迷走神经流出和抑制动脉压力反射抑制MSNA。为了实现这些目标，将对120名血压正常的非肥胖者(n=60；BMI<25 kg/m2)和肥胖者(n=60；BMI<28；BMI<35 kg/m2)进行研究。身体成分将通过双能X射线吸收测量仪测量，腹部内脏脂肪将使用计算机断层扫描进行量化。呼吸性窦性心律失常(功率谱分析)将被用来估计心脏迷走神经对心率的调制，而显微神经学(腓神经)技术将被用来在静息状态下测量节后MSNA。注射硝普钠和苯肾上腺素以及同时获得颈动脉内径的B型超声图像将用于评估动脉压力感受性反射对心脏迷走神经流出和MSNA的控制。将使用两种实验方法：1)对腹部内脏脂肪上40%和下40%的非肥胖者和肥胖者进行横断面比较；2)进食不足(仅限肥胖者)，以使体重减少10%，并显著减少全身和腹部内脏脂肪。所有测量将在为期4周的体重稳定期后进行，在此期间，大量营养素的组成和钠的摄入量水平是标准化的。这项研究的结果将提供有关腹部内脏脂肪过度堆积的自主循环机制和后果的新的生理学和临床重要信息。考虑到越来越多的人认识到自主循环功能障碍可能是一些心血管疾病(高血压；冠状动脉疾病)和代谢性疾病(NIDDM)状态的原因因素，这一信息至关重要，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.