The sympathetic nervous system as a target for intervention in obesity.
The sympathoadrenal system plays an important role in the regulation of both energy intake and energy expenditure (EE), and the sympathetic nervous system (SNS) offers a dual target for pharmacological intervention directed at weight loss in obese patients. The sizes of the fat-free mass and fat mass are the major determinants of resting EE, but studies using different techniques have shown that differences in sympathetic activity can account for an additional proportion of the variation between individuals. Differences in thermogenic responses to food can also be explained by different abilities to activate the sympathoadrenal system. A low resting EE for a given body composition is one manifestation of the genetically determined predisposition to obesity. A low sympathetic activity may be one factor responsible but, as yet, no conclusive evidence has been found. In dietary treatment programmes of obesity, patients with high levels of EE and greater SNS activity achieve greater long-term weight loss than those with lower levels. Pharmacological stimulation with sympathomimetic compounds suppresses appetite and increases energy expenditure through stimulation of beta 1, beta 2, and beta 3-receptor subtypes. During chronic treatment, the beta 3-mediation may predominate due to down-regulation of beta 1- and beta 2-receptors. An improved understanding of the aetiological role of the SNS in the development of obesity in genetically susceptible individuals may permit tailoring of pharmacological intervention.
Astrup
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Research Department of Human Nutrition and Centre of Food Research, Royal Veterinary and Agricultural University, Copenhagen, Denmark.
D004734:Energy Metabolism / Q000502:physiology; D006801:Humans; D009765:Obesity / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*; D011941:Receptors, Adrenergic / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology*; D015431:Weight Loss / Q000502:physiology
D011941:Receptors, Adrenergic