Regional sympathetic nervous activity and oxygen consumption in obese normotensive human subjects

BACKGROUND: Disturbed sympathetic nervous function may be of importance in obesity; sympathetic underactivity could contribute to deficient thermogenesis, positive energy balance, and weight gain, while in contrast, sympathetic nervous overactivity would predispose to the development of obesity-related hypertension. Global indices of sympathetic nervous system (SNS) function such as plasma or urinary norepinephrine (NE) have been unable to define SNS status in obesity. Since regional SNS activity can be altered in the absence of global changes, we investigated SNS activity in the heart, kidneys, and hepatomesenteric bed in healthy human subjects across a wide body mass index (BMI) range of between 19.6 and 35.5. METHODS AND RESULTS: Whole-body and regional plasma NE kinetics using 3H]-labeled NE were assessed. Regional oxygen consumption was measured by combining arteriovenous differences in oxygen content and regional blood flow. Arterial plasma NE and whole-body plasma NE spillover were unrelated to BMI. With a BMI cutoff of 27, mean cardiac NE spillover was 46% lower in the obese subjects when compared with the lean subjects (P=.017). Renal NE spillover was significantly correlated with BMI (r=.668, P=.001), the mean value in the obese subjects being more than twice that in the lean subjects. Hepatomesenteric NE spillover was comparable in lean and obese subjects. Renal and hepatomesenteric oxygen consumption were both significantly higher in the obese subjects compared with lean subjects. CONCLUSIONS: Regional SNS activity is heterogeneous in the obese state. Important regional alterations, which may be clinically relevant, occur in the absence of changes in global indices of sympathetic nervous function. The enhanced renal NE spillover in obesity may have implications for the development of hypertension in this group, whereas the low cardiac sympathetic tone would be expected to be cardioprotective. Enhanced visceral oxygen consumption evident in the kidneys and hepatomesenteric circulation in proportion to body mass contributes to the greater resting oxygen consumption in obesity.