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Bound Leptin and Sympathetic Outflow in Nonobese Men

Helios-Kliniken-Berlin (J.T., J.J., C.S., A.M.S., F.C.L.), Franz Volhard Cardiovascular Research Center, Medical Faculty of the Charité, Humboldt-University, 13125 Berlin, Germany; Department of Endocrinology (G.B.), Med. Hochschule Hannover, 30625 Hannover, Germany; General Clinical Research Center (A.D.), Autonomic Dysfunction Unit, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2195; and Medicina Interna II (R.F.), Ospedale L. Sacco, 20157 Milano, Italy

Address all correspondence and requests for reprints to: Jens Tank, M.D., Franz Volhard Cardiovascular Research Center, Wiltberg Strasse 50, 13125 Berlin, Germany. E-mail: tank{at}fvk-berlin.de.

Leptin exists in a free form and a receptor-bound form. Protein-bound rather than free leptin levels may be associated with regulation of muscle sympathetic nerve activity (MSNA). We determined MSNA and bound leptin concentrations in 25 men [age, 29 ± 6 yr, body mass index (BMI), 24 ± 3 kg/m²]. Baroreflex sensitivity was measured using phenylephrine and nitroprusside infusions. We measured bound leptin in patients with central (multiple system atrophy, n = 8; age, 59 ± 8 yr; BMI, 23 ± 2 kg/m²) and peripheral autonomic failure (pure autonomic failure, n = 4; age, 71 ± 10 yr; BMI, 25 ± 3 kg/m²). MSNA was correlated with protein-bound leptin concentrations (r² = 0.35; P < 0.01) but not with free leptin levels (r² = 0.09). MSNA at baseline was 15 ± 2 bursts x minutes^-1 in subjects with lower and 24 ± 3 bursts x minutes^-1 in subjects with higher bound leptin concentrations (P < 0.05). Blood pressure as well as baroreflex regulation of heart rate and MSNA was similar in both groups. Phenylephrine and nitroprusside responses were similar. Patients with multiple system atrophy and autonomic failure featured similar bound leptin levels. We conclude that protein-bound rather than free leptin levels are correlated with basal sympathetic outflow in normotensive, nonobese men. This relationship cannot be explained by a direct central nervous effect of protein-bound leptin. Instead, protein-bound leptin may increase sympathetic vasomotor tone indirectly via a baroreflex mechanism.

This work was supported in part by Deutsche Forschungsgemeinschaft Grant Jo 284/3-1. J.J. is the recipient of a Helmholtz scholarship of the Max-Delbrueck-Center of Molecular Medicine.

Abbreviations: BMI, Body mass index; high-bl, high protein-bound leptin plasma levels; low-bl, low protein-bound leptin plasma levels; MSNA, muscle sympathetic nerve activity; NTP, nitroprusside; PHE, phenylephrine.

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