Sympathetic nervous activity in carriers of MC4R mutations

Dysfunctions of the sympathetic nerve system may contribute to the development of obesity. The melanocortin system is critically involved in maintenance of energy balance. Activation of the melanocortin-4 receptor (MC4-R) leads to a decrease of appetite and an elevation of sympathetic nerve activity (SNA). Recently it has been shown that known sympathoactivation to leptin is mediated by the melanocortin system and a functional MC4R is a prerequisite for the development of hypertension associated with obesity in animal model. To test the hypothesis that functional mutations of the MC4-R lead to a diminished SNA in humans, ten carriers of MC4R mutations and a control group of 17 subjects who were matched for gender, body mass index (BMI) and age were investigated. Muscle sympathetic nerve activity (MSNA) recordings from the superficial peroneal nerve were obtained by microneurography and frequency domain analysis of heart rate variability (HRV) were performed (Fourier transformation for determination of low-frequency (LF, 0.045–0.15Hz) and high-frequency (HF, 0.15–1.0Hz) components). Despite a significantly lower heart rate (MC4R-mut. 64.7±2.9; contr. 73.3±2.7; p<0.05) in carriers of MC4R mutations, MSNA (MC4R-mut. 22.7 bursts/min±4.6; contr. 22.1 bursts/min±2.1) was not different. Blood pressure, LF- and HF band were also similar in both groups. In both groups MSNA was positively correlated with age (MC4R-mut. R=0.61; p=0.059; contr. R=0.67, p=0.004). In conclusion, sympathetic nerve activity measured by MSNA and LF are not decreased in carriers of MC4-R mutations. Since a low heart rate is rather related to a strong parasympathetic input to the heart, the cause for the low heart rate in this group remains unclear at present.