Body weight and sympathetic activity
In experimental and clinical studies, it has been shown that overweight persons exhibit an increased activity of the sympathetic nervous system. It was reported by Scherrer et al. (1)  that skeletal muscle sympathetic nerve activity correlates with body mass index, whereby the correlation already starts with a body mass index of approx. 23. Thus, a raised sympathetic activity is not solely a problem of obese persons, i.e. BMI greater 30, but is present already in moderately overweight persons.
    It might be asked why the body responds to a rise in body weight by increasing sympathetic activity. It can be speculated that during evolution,  the body had to adjust to periods of food shortage by reducing energy expenditure by downregulating sympathetic activity, i.e. bradycardia and reduced basal metabolism. Only in recent decades, living conditions have changed in a manner which brings the body in a situation where he has to deal with a chronically raised caloric intake. It appears that the body uses the same mechanisms acquired during centuries of intermittent food shortage and raises the sympathetic activity in parallel with the caloric intake. One of the consequences of this chronically increased sympathetic activity is a high incidence of hypertension and insulin resistance and the consecutive diabetes mellitus type-2.
It has also been reported that urinary catecholamine metabolites are increased in parallel with the rise in body weight judged either by the body mass index (BMI) or the waist-to-hip ratio (2).

The fact that an increase in body weight is associated with a raised sympathetic activity may be surprising. Shortly after food intake, sympathetic activity is either unchanged or reduced which is associated with a raised parasympathetic activity. This postprandial state is characterized by the absorption of nutrients and is dominated by the parasympathetic system activity.

Acute caloric intake and parasympathetic activity

By contrast, a chronically increased caloric intake leads to a raised sympathetic activity which - when referred to the physical activity - has to be rated as sympathetic overactivity. It appears that the parasympathetic activity remains unaltered. This chronic rise in sympathetic activity has various adverse effects. It is currently not known how this increase in centrally mediated sympathetic overactivity is triggered. According to one hypothesis, a chronically high caloric intake leads to insulin resistance which requires hyperinsulinemia to maintain normal blood glucose levels. The hyperinsulinemia is expected to stimulate sympathetic acitivity. It is, however, also possible that a high caloric intake directly stimulates sympathetic outflow of the brain.

Chronically raised caloric intake and sympathetic overactivity  

Since BMI, waist-to-hip ratio or abdominal visceral fat are closely linked to sympathetic outflow of the brain, a drug which reduces an increased sympathetic outflow of the brain represents a logical therapy for interfering with overweight associated diseases such as hypertension and insulin resistance. Moxonidine is currently the only drug which reduces sympathetic outflow with minimal adverse side effects.

1. Scherrer U, Randin D, Tappy L, Vollenweider P, Jequier E, Nicod P: Body fat and sympathetic nerve activity in healthy subjects. Circulation 1994;89:2634-2640