The Role of the Autonomic Nervous System in the Pathophysiology of Obesity

Daniela Guarino, Monica Nannipieri, Giorgio Iervasi, Stefano Taddei, Rosa Maria Bruno, Daniela Guarino, Monica Nannipieri, Giorgio Iervasi, Stefano Taddei, Rosa Maria Bruno

Abstract

Obesity is reaching epidemic proportions globally and represents a major cause of comorbidities, mostly related to cardiovascular disease. The autonomic nervous system (ANS) dysfunction has a two-way relationship with obesity. Indeed, alterations of the ANS might be involved in the pathogenesis of obesity, acting on different pathways. On the other hand, the excess weight induces ANS dysfunction, which may be involved in the haemodynamic and metabolic alterations that increase the cardiovascular risk of obese individuals, i.e., hypertension, insulin resistance and dyslipidemia. This article will review current evidence about the role of the ANS in short-term and long-term regulation of energy homeostasis. Furthermore, an increased sympathetic activity has been demonstrated in obese patients, particularly in the muscle vasculature and in the kidneys, possibily contributing to increased cardiovascular risk. Selective leptin resistance, obstructive sleep apnea syndrome, hyperinsulinemia and low ghrelin levels are possible mechanisms underlying sympathetic activation in obesity. Weight loss is able to reverse metabolic and autonomic alterations associated with obesity. Given the crucial role of autonomic dysfunction in the pathophysiology of obesity and its cardiovascular complications, vagal nerve modulation and sympathetic inhibition may serve as therapeutic targets in this condition.

Keywords: adipose tissue; autonomic nervous system; energy expenditure; gut hormones; obesity; vagal nerve blockade; vagal nerve stimulation; weight loss.

Figures

Figure 1
Figure 1
Peripheral signals of satiety and gastric emptying reach the nucleus of the solitary tract/area postrema complex (NST/AP) via afferent vagal nerves (red line). The NTS projects to the dorsal motor nucleus (DMN). This pathway modulates intestinal motility and secretion, glucose production and pancreatic secretion via efferent vagal nerves (blue line). The suggested site of action of vagal nerve stimulation (VNS) is indicated by the dotted green lines, while mechanism of weight loss hypothesized vagal nerve blockade includes decrease in gastric emptying, increase in gut hormones release and inhibition of pancreatic esocrine secretion (dotted orange lines).
Figure 2
Figure 2
Cold- or diet-stimulated sympathetic activation results in mobilization of free fatty acids (FFA) by white adipose tissue (WAT) and regulation of brown adipose tissue (BAT) thermogenesis. The principal substrate for BAT is constituted by fatty acids to increase energy expenditure inducing heat production. Chronic sympathetic nervous system (SNS) activation also induces the conversion of “beige” adipose tissue in WAT, which also contribute to adaptive thermogenesis.
Figure 3
Figure 3
Mechanisms responsible for the occurrence of sympathetic activation in obesity-related hypertension. Prolonged sympathetic nervous system (SNS) overactivity might induce weight gain, due to downregulation of beta-adrenoceptors, thus reducing the capacity to dissipate excessive calories.

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