Change in sympathetic nerve firing pattern associated with dietary weight loss in the metabolic syndrome

Elisabeth Lambert

doi:10.3389/fphys.2011.00052

Abstract

Sympathetic activation in subjects with the metabolic syndrome (MS) plays a role in the pathogenesis of cardiovascular disease development. Diet-induced weight loss decreases sympathetic outflow. However the mechanisms that account for sympathetic inhibition are not known. We sought to provide a detailed description of the sympathetic response to diet by analyzing the firing behavior of single-unit sympathetic nerve fibers. Fourteen subjects (57 ± 2 years, nine men, five females) fulfilling ATP III criteria for the MS underwent a 3-month low calorie diet. Metabolic profile, hemodynamic parameters, and multi-unit and single-unit muscle sympathetic nerve activity (MSNA, microneurography) were assessed prior to and at the end of the diet. Patients’ weight dropped from 96 ± 4 to 88 ± 3 kg (P < 0.001). This was associated with a decrease in systolic and diastolic blood pressure (−12 ± 3 and −5 ± 2 mmHg, P < 0.05), and in heart rate (−7 ± 2 bpm, P < 0.01) and an improvement in all metabolic parameters (fasting glucose: −0.302.1 ± 0.118 mmol/l, total cholesterol: −0.564 ± 0.164 mmol/l, triglycerides: −0.414 ± 0.137 mmol/l, P < 0.05). Multi-unit MSNA decreased from 68 ± 4 to 59 ± 5 bursts/100 heartbeats (P < 0.05). Single-unit MSNA indicated that the firing rate of individual vasoconstrictor fibers decreased from 59 ± 10 to 32 ± 4 spikes/100 heart beats (P < 0.05). The probability of firing decreased from 34 ± 5 to 23 ± 3% of heartbeats (P < 0.05), and the incidence of multiple firing decreased from 14 ± 4 to 6 ± 1% of heartbeats (P < 0.05). Cardiac and sympathetic baroreflex function were significantly improved (cardiac slope: 6.57 ± 0.69 to 9.57 ± 1.20 ms·mmHg−1; sympathetic slope: −3.86 ± 0.34 to −5.05 ± 0.47 bursts/100 heartbeats·mmHg−1, P < 0.05 for both). Hypocaloric diet decreased sympathetic activity and improved hemodynamic and metabolic parameters. The sympathoinhibition associated with weight loss involves marked changes, not only in the rate but also in the firing pattern of active vasoconstrictive fibers.

Highlights

IntroductionWhile uncomplicated obesity is accompanied by an increase in muscle sympathetic nerve activity (MSNA; Lambert et al, 2010b), sympathetic activation is more pronounced in obese subjects with central fat accumulation (Alvarez et al, 2002; Grassi et al, 2004), hypertension (Grassi et al, 2000; Lambert et al, 2007), obstructive sleep apnoea (Grassi et al, 2005b), and when associated with the metabolic syndrome (MS; Grassi et al, 2005a)
Sympathetic activation is a hallmark in obesity
We examined the effects of diet-induced weight loss on the autonomic nervous system in middle aged individuals with the metabolic syndrome (MS) by combining multi-unit and single-unit muscle sympathetic nerve activity (MSNA) recordings with the assessment of cardiac and sympathetic baroreflex function

Summary

Introduction

While uncomplicated obesity is accompanied by an increase in muscle sympathetic nerve activity (MSNA; Lambert et al, 2010b), sympathetic activation is more pronounced in obese subjects with central fat accumulation (Alvarez et al, 2002; Grassi et al, 2004), hypertension (Grassi et al, 2000; Lambert et al, 2007), obstructive sleep apnoea (Grassi et al, 2005b), and when associated with the metabolic syndrome (MS; Grassi et al, 2005a) Such sympathoexcitation is most likely involved in the generation and aggravation of the hemodynamic and metabolic profile of obese individuals as it has been shown to favor blood pressure (BP) elevation (Grassi et al, 2004), reduced insulin sensitivity and increased serum triglycerides (Landsberg, 2001) and to be associated with left ventricular hypertrophy (Schlaich et al, 2003) and dysfunction (Grassi et al, 2009). We recently demonstrated that in subjects with obesity, recruitment of additional fibers was the central mechanism by which sympathoexcitation occurs because the firing rate www.frontiersin.org

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