Sympathetic System Activity in Obesity and Metabolic Syndrome

Abstract

Obesity is a very common disease worldwide, resulting from a disturbance in the energy balance. The metabolic syndrome is also a cluster of abnormalities with basic characteristics being insulin resistance and visceral obesity. The major concerns of obesity and metabolic syndrome are the comorbidities, such as type 2 diabetes, cardiovascular disease, stroke, and certain types of cancers. Sympathetic nervous system (SNS) activity is associated with both energy balance and metabolic syndrome. Sympathomimetic medications decrease food intake, increase resting metabolic rate (RMR), and thermogenic responses, whereas blockage of the SNS exerts opposite effects. The contribution of the SNS to the daily energy expenditure, however, is small ( approximately 5%) in normal subjects consuming a weight maintenance diet. Fasting suppresses, whereas meal ingestion induces SNS activity. Most of the data agree that obesity is characterized by SNS predominance in the basal state and reduced SNS responsiveness after various sympathetic stimuli. Weight loss reduces SNS overactivity in obesity. Metabolic syndrome is characterized by enhanced SNS activity. Most of the indices used for the assessment of its activity are better associated with visceral fat than with total fat mass. Visceral fat is prone to lipolysis: this effect is mediated by catecholamine action on the sensitive beta(3)-adrenoceptors found in the intraabdominal fat. In addition, central fat distribution is associated with disturbances in the hypothalamo-pituitary-adrenal axis, suggesting that a disturbed axis may be implicated in the development of the metabolic syndrome. Furthermore, SNS activity induces a proinflammatory state by IL-6 production, which in turn results in an acute phase response. The increased levels of inflammatory markers seen in the metabolic syndrome may be elicited, at least in part, by SNS overactivity. Intervention studies showed that the disturbances of the autonomic nervous system seen in the metabolic syndrome are reversible.

Intracerebroventricular Administration of Neuropeptide Y Induces Hepatic Insulin Resistance via Sympathetic Innervation

“…Several of the components of the metabolic syndrome, like hypertension, obesity, and insulin resistance, are associated with adrenergic overdrive. In contrast, it has also been reported that the response of the sympathetic nervous system to various stimuli is diminished in obese humans (47)(48)(49), However, most investigators agree that obesity is marked by enhanced sympathetic tone in most tissues, at least in the basal state (47-49 and references therein). Our data suggest that elevation of hypothalamic NPY levels as a corollary of leptin resistance may contribute to sympathetic overdrive, hepatic insulin resistance, and increased glucose production in high-fat-fed rodents and man.…”

Attenuation of the cardiovascular and metabolic complications of obesity in CD14 knockout mice

“…In WT mice, obesity was accompanied by sympathetic nervous system activation, as evaluated by the excretion of noradrenaline in 24-hour urine. Sympathetic overactivity has been consistently reported in both animal models and human obesity, and has been proposed to underlie blood pressure elevation in this disease (Lembo et al, 1992;Tentolouris et al, 2006). In fact, several experimental and clinical studies showed a positive correlation between the urinary excretion of noradrenaline and hypertension (Aneja et al, 2004).…”

Interaction Between Sympatho-Adrenal Activity and Immune Mediators in Patients With Metabolic Syndrome

“…В развитии и прогрессировании ИР и ГИ и свя-занных с ней метаболических расстройств важную роль играют нейрогуморальные нарушения с повы-шением активности симпатико-адреналовой системы (САС) [2,3]. Однако в условиях ИР гиперактивация САС приводит к симпатической стимуляции сердца, сосудов, почек и появлению артериальной гиперто-нии (АГ) [1,2,4].…”

“…и акти-вируют специфические рецепторы клеток-мишеней. Тесное взаимодействие нейрогуморальной и иммун-ной систем обеспечивает присутствие рецепторов к норадреналину на иммунных клетках [7,8]. Симпа-тическая нервная система (СНС) регулирует цирку-ляцию и пролиферацию лимфоцитов, а также выра-ботку ими иммунокомпетентных клеток и других биологически активных веществ посредством взаи-модействия норадреналина с рецепторами иммунных клеток [7,9].…”