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

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.

Weight loss induced by deep transcranial magnetic stimulation in obesity: A randomized, double‐blind, sham‐controlled study

“…In animal behavioural models of depression, repetitive TMS of the brain was found to significantly upregulate β‐adrenergic receptors in the frontal cortex, after only 10 days of treatment, suggesting a possible involvement of the adrenergic system in the mechanisms of action of the dTMS. A dysregulation of the autonomic nervous system also plays a role in the pathophysiology of obesity, being involved in the modulation of the appetite/satiety signal and energy expenditure . On one hand, the observed increase of epinephrine after 5 weeks of HF dTMS in obese people could affect the food craving associated with obesity, although the underlying mechanisms of action need to be clarified.…”

Sex differences in sympathetic activity in obesity and its related hypertension

“…15,16 In contrast, some researchers have suggested that sustained sympathetic activation might cause an increase rather than a decrease in body weight due to reduced capacity to dissipate excessive calories mediated by downregulation of β adrenoceptors. [17][18][19] Regardless of augmented sympathetic activity in the skeletal muscle and kidneys, obese normotensive men were found to have reduced cardiac sympathetic tone. 14 Indeed, obesity without its related hypertension elicits a selective and differentiated increase in sympathetic activity rather than generalized sympathetic activation.…”

“…14 Indeed, obesity without its related hypertension elicits a selective and differentiated increase in sympathetic activity rather than generalized sympathetic activation. 19…”

“…24,58 Chronic hyperinsulinemia is a feature of obesity aimed at restoring energy balance and limiting weight gain in a compensatory fashion; however, it may act as a maladaptive mechanism resulting in sympathetic overactivity. 16,19 Insulinelicited sympathetic activation has been proposed through both central and peripheral actions. Insulin receptors are widely distributed in the human brain, and insulin enters the central nervous system through the blood-brain barrier by receptormediated transport.…”

Autonomic nervous system might be related with circadian rhythms and have the intricate effects in obstructive sleep apnea with metabolic syndrome

“…4,5 Autonomic dysfunction in OSA patients may be related not only to the factors above but also to the metabolic condition in OSA, since as some high quality of works reported that the impaired autonomic control may stem from injury to central and peripheral neuron resulting from metabolic damage and in turn the autonomic dysfunction could lead to further metabolic morbidity later in life and even mortality. [6][7][8] Substantial evidence exists to support the strong associations between ANS dysfunction and hypertension and CVD such as coronary heart disease and mortality. 9,10 Thus, it will be important to gain further insights into…”