Sympathetic Activation in Obesity

Abstract

The hypothesis that human obesity is associated with a state of adrenergic overdrive dates back to ≈50 years ago, when a group of American investigators noted that sympathetic function was indeed altered in the obese subject.1 Since then, many studies have attempted to investigate whether and to what extent sympathetic activation is a hallmark of the autonomic profile of the obese state. The results, which have also been included in a meta-analysis,2 although suggestive for a hyperadrenergic state, did not permit any definite conclusion on this issue to be drawn. Several factors may account for these inconclusive results. First, the data collected were mainly based on the biochemical assay of plasma norepinephrine or its urinary metabolites, that is, an approach known to have a limited reproducibility and sensitivity in detecting the adrenergic abnormalities characterizing a physiological or a pathophysiological state.3 Furthermore, plasma norepinephrine concentration relies on a variety of biological processes taking place both at a synaptic and at a postsynaptic level, such as the reuptake of the neurotransmitter by the adrenergic nerve terminals and the tissue clearance process of norepinephrine, as well as its functional role as a cotransmitter with epinephrine.3 These complex steps make hard to establish whether and to what extent an elevation in circulating levels of norepinephrine (or its urinary metabolites) mirrors a true increase in central adrenergic outflow or whether it rather reflects an impairment of the physiological processes mentioned above taking place at a peripheral neural level. More stringent evidence on the adrenergic overdrive characterizing the obese state …