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Neuroadrenergic dysfunction in obesity: an overview of the effects of weight loss

Straznicky, Nora E; Lambert, Gavin W; Lambert, Elisabeth A

doi: 10.1097/MOL.0b013e3283329c62
Nutrition and metabolism: Edited by Paul Nestel and Ronald P. Mensink

Purpose of review The prevalence of obesity is rising to epidemic proportions worldwide, and in tandem so is that of type 2 diabetes. Neuroadrenergic abnormalities, comprising increased resting sympathetic nervous system activity and blunted sympathetic neural responsiveness are recognized features of metabolic syndrome obesity, which contribute importantly to both the pathophysiology and adverse clinical prognosis of this high-risk population. Weight loss is recommended as first-line treatment for obesity. This review examines the effects of nonpharmacological weight loss on sympathetic nervous system function under basal and stimulated conditions.

Recent findings Human weight loss trials show that even moderate weight reduction is accompanied by significant attenuation in resting whole-body norepinephrine spillover rate and muscle sympathetic nerve activity, an improvement in cardiac autonomic modulation, and a reversal of blunted sympathetic responsiveness at both peripheral and central nervous system levels. Recent findings underscore the relevance of insulin resistance in mediating blunted sympathetic responsiveness to endogenous hyperinsulinemia induced by glucose ingestion. Impaired insulin transport across the blood–brain barrier may be one mechanism mediating these effects. Weight loss reverses blunted sympathetic responsiveness to glucose, which has implications for postprandial energy expenditure and body weight homeostasis.

Summary The autonomic dysfunction of obesity is reversible with weight loss, highlighting the importance of lifestyle intervention as a key therapeutic modality.

Human Neurotransmitters Laboratory, Baker IDI Heart & Diabetes Institute, Melbourne, Victoria, Australia

Correspondence to Dr Nora E. Straznicky, Human Neurotransmitters Laboratory, Baker IDI Heart & Diabetes Institute, PO Box 6492, St Kilda Road Central, Melbourne, VIC 8008, Australia Tel: +61 3 8532 1371; fax: +61 3 8532 1100; e-mail:

© 2010 Lippincott Williams & Wilkins, Inc.