Long-Term Sympathoinhibitory Effects of Surgically Induced Weight Loss in Severe Obese Patients

Abstract

L ong-term prospective studies have recently shown that bariatric surgery significantly reduces the risk of death in severely obese patients.1 This has been confirmed by retrospective analyses of a large cohort of obese individuals in whom surgery-related reductions in body weight were associated with a significant reduction in death rate compared with obese individuals followed under dietary and medical treatment. [2][3][4] It is a widespread belief that the protective effect of bariatric surgery in obese patients may perhaps be related to a reduction of body weight per se but that the concomitant improvement of the array of risk factors commonly associated with obesity, for example, alterations in lipid and glucose metabolism, is likely to play a major role. [5][6][7] In this context, however, little attention has to date been given to whether bariatric surgery is also associated with the improvement of another adverse phenomenon of obesity (ie, sympathetic activation). 8,9 The only information available comes from 3 studies that assessed sympathetic tone by making use of spectral analysis of heart rate signal or 24-hour norepinephrine urinary excretion [10][11][12] (ie, approaches that display major intrinsic limitations not allowing to provide any direct insight on the effects of the intervention on central sympathetic outflow, as the microneurographic technique only allows to achieve 13 .) The issue has pathophysiological and clinical relevance because sympathetic activation has been shown to be an adverse prognostic factor in several clinical conditions.14-17 Furthermore, evidence has been obtained that sympathetic overdrive may cause or worsen insulin resistance, 18,19 thus contributing to a common metabolic alteration in obesity.Abstract-Weight loss improves insulin sensitivity and exerts sympathomodulatory effects. No data, however, are available on the effects of the weight loss induced by vertical sleeve gastrectomy on sympathetic neural drive, insulin sensitivity, and their reciprocal cross talks. In 10 severe obese hypertensives (age, 54.0±2.3 years [mean±SEM]), we measured sphygmomanometric blood pressure, heart rate, body mass index, homeostatic model assessment index, plasma leptin, muscle sympathetic nerve traffic (microneurography), and baroreflex sensitivity (vasoactive drug technique). Measurements were performed 2 to 3 days before surgery and repeated 6 and 12 months after the procedure. Ten matched hypertensive obeses not undergoing gastrectomy served as controls. Six months after bariatric surgery, a significant (P<0.05) reduction in body mass index (−9.1±1.4 kg/m 2 ), sphygmomanometric systolic blood pressure (−10.2±4.5 mm Hg), heart rate (−11.0±2.4 bpm), homeostatic model assessment index (−3-3±1.3 AU), plasma leptin (−53.6±8.8 μg/L), and muscle sympathetic nerve traffic (−15.0±3.4 bursts/100 heart beats) was observed. The weight loss, the plasma leptin reduction, and the sympathetic inhibition were maintained after 12 months, whereas homeostatic model assessment index showed a tendency ...

Should the sympathetic nervous system be a target to improve cardiometabolic risk in obesity?

“…Similar results were noticed 6 mo and 1 yr after vertical sleeve gastrectomy where subjects showed in addition to metabolic and hemodynamic improvements, a substantial decrease in MSNA (142). The effects of sleeve gastrectomy on sympathetic tone may be mediated, at least in part, by the reduction in the elevated levels of plasma leptin but also by an improvement in baroreflex function (142). Surprisingly, it was recently documented that following gastric bypass surgery, despite the low-resting MSNA, there was an almost complete absence of sympathetic contribution to resting energy expenditure, suggesting that this may have important consequences for the maintenance of weight loss after gastric bypass (29) ( Table 1).…”

“…In addition, the weight loss was associated with a substantial reduction in MSNA and improvement in blood pressure and renal function (88). Similar results were noticed 6 mo and 1 yr after vertical sleeve gastrectomy where subjects showed in addition to metabolic and hemodynamic improvements, a substantial decrease in MSNA (142). The effects of sleeve gastrectomy on sympathetic tone may be mediated, at least in part, by the reduction in the elevated levels of plasma leptin but also by an improvement in baroreflex function (142).…”

New developments in the pathogenesis of obesity-induced hypertension

“…Seravalle et al [61] recently extended previous findings on the sympathetic nervous system in human hypertension and obesity with the demonstration of another beneficial effect of bariatric surgery, namely pronounced and sustained sympathoinhibition after gastric bypass in patients with severe obesity. Renal sympathetic denervation attenuates sodium and water retention and the rise in arterial pressure in a high-fat diet model of obesity in dogs.…”

QT Interval Shortening After Bariatric Surgery Depends on the Applied Heart Rate Correction Equation

“…For instance, free fatty acids (FFAs) may represent a good candidate since one previous study [22] has found a correlation between the decline in circulating FFA levels and the QTc interval length reduction after diet-induced weight loss. Also, the adipose tissue hormone leptin may be a good candidate since it was shown to decline after bariatric surgery along with a marked reduction in SNS activity [43]. Beside these putative hormonal mediators, other mechanisms may also contribute to the weight loss associated reduction in QT interval length.…”