Sympathetic function in carriers of MC4R mutations
D Heutling1, F Sayk2, C Dodt2, HL Fehm2, T Frank2, A Hinney3, J Hebebrand3 & H Lehnert4
Activation of the melanocortin-4 receptor (MC4R) leads to a decrease of appetite and an elevation of sympathetic nerve activity (SNA). The sympathoexcitatory property of 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 MC4R 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. Frequency domain analysis of heart rate variability (HRV) was also performed for low frequency (LF, 0.0450.15 Hz) and high-frequency (HF, 0.151.0 Hz) components. Carriers with MC4R mutations showed a significantly lower heart rate. However, neither HRV parameters of cardiac sympathetic activity nor MSNA differed between both groups. Results are shown in the following table:
Blood pressure was 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 carriers of MC4R mutations but not in the control group heart rate was positively correlated with HOMA-IR as an marker of insulin sensitivity (MC4R-mut. R=−0.27; P=0.45; contr. R=0.65, P=0.005). In conclusion, both sympathetic nerve activity to the muscle vascular bed and to the heart is not altered in carriers of MC4R mutations. Although the lower heart rate could indicate altered autonomic function in MC4R mutation carriers our study does not indicate to a depressed sympathetic nerve activity to the heart or the muscle vascular bed.