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

Abstract

The sympathetic nervous system (SNS) plays a key role in both cardiovascular and metabolic regulation; hence, disturbances in SNS regulation are likely to impact on both cardiovascular and metabolic health. With excess adiposity, in particular when visceral fat accumulation is present, sympathetic activation commonly occurs. Experimental investigations have shown that adipose tissue releases a large number of adipokines, cytokines, and bioactive mediators capable of stimulating the SNS. Activation of the SNS and its interaction with adipose tissue may lead to the development of hypertension and end-organ damage including vascular, cardiac, and renal impairment and in addition lead to metabolic abnormalities, especially insulin resistance. Lifestyle changes such as weight loss and exercise programs considerably improve the cardiovascular and metabolic profile of subjects with obesity and decrease their cardiovascular risk, but unfortunately weight loss is often difficult to achieve and sustain. Pharmacological and device-based approaches to directly or indirectly target the activation of the SNS may offer some benefit in reducing the cardiometabolic consequences of obesity. Preliminary evidence is encouraging, but more trials are needed to investigate whether sympathetic inhibition could be used in obesity to reverse or prevent cardiometabolic disease development. The purpose of this review article is to highlight the current knowledge of the role that SNS plays in obesity and its associated metabolic disorders and to review the potential benefits of sympathoinhibition on metabolic and cardiovascular functions.

Increased peripheral vascular disease risk progressively constrains perfusion adaptability in the skeletal muscle microcirculation

“…While certainly some of these effects are the result of the changes to endothelial function impacting the constrictor responses (29,42,43), there is previous evidence to support increases in adrenergic activity (6), receptor sensitivity (52), or downstream signaling gain (41) as potential contributors to increased constrictor responses in many of these models. While this would potentially reduce attractor variability further and would represent an additional, and possibly extremely robust, depressor of arteriolar function and flexibility in the control of tissue perfusion, it is unclear that a simple "increase in adrenergic constrictor reactivity" accurately represents the prevailing condition in conditions of elevated PVD risk that are associated with obesity and hypertension (28,30,37). If this was a widespread phenomenon, it would result in either enormous elevations in perfusion pressure or dramatic reductions in blood flow.…”

The adipokine chemerin amplifies electrical field-stimulated contraction in the isolated rat superior mesenteric artery

“…This artery was chosen for several reasons. 1) The superior mesenteric artery is in the viscera, and it is visceral fat that is associated with the greatest cardiovascular risk (21,46,47).…”

Cardiometabolic Risks in Polycystic Ovary Syndrome: Non-Traditional Risk Factors and the Impact of Obesity

“…In the general population, obesity, in particular central obesity [144] , is associated with increased SNS activity, even in the absence of hypertension [145] contributing to left ventricular hypertrophy and cardiovascular dysfunction [146] . MSNA is at least 50% higher in obese than lean subjects, indicating SNS activation [144] .…”

“…MSNA is at least 50% higher in obese than lean subjects, indicating SNS activation [144] . Potential mediators of obesity-associated SNS stimulation include (1) adipokines [145,147] and (2) stimulation of pro-opiomelanocortin neurons, with subsequent activation of the melanocortin receptors in the central nervous system [148] . Chronic SNS activation may be associated with impaired catecholaminergic signalling in adipose tissue, resulting in reduced metabolism and increased IR [149] .…”