PHARMACODYNAMICS Influences of levodopa on adipose tissue and skeletal muscle metabolism in patients with idiopathic Parkinson’ s disease Frauke Adams & Michael Boschmann & Elmar Lobsien & Andreas Kupsch & Axel Lipp & Gabriele Franke & Marie Charlotte Leisse & Juergen Janke & Simone Gottschalk & Joachim Spranger & Jens Jordan Received: 7 February 2008 / Accepted: 27 June 2008 / Published online: 30 July 2008 # Springer-Verlag 2008 Abstract Objective The substantial weight loss in Parkinson’ s patients may be related to direct influences of levodopa treatment on fat mobilization/oxidation. We assessed systemic and local metabolic responses to levodopa/benserazide in patients with idiopathic Parkinson’ s disease. Methods We studied 10 Parkinson’ s disease patients and examined adipose tissue and skeletal muscle metabolism directly with microdialysis. We monitored dialysate con- centrations of ethanol, glucose, lactate, pyruvate, and glycerol to assess tissue blood flow and metabolism before and after levodopa/benserazide intake. We also conducted in vitro studies on adipocytes from healthy women. Results Levodopa/benserazide increased serum levodopa, 3,4-dihydroxyphenylacetic acid (DOPAC), and norepineph- rine (P <0.01). Serum adipose tissue and skeletal muscle glycerol did not change or decreased. Adipose tissue glycerol was inversely correlated with serum levodopa concentrations (P <0.05). In isolated adipocytes, levodopa attenuated isoproterenol-induced glycerol release (P <0.05). Conclusion Levodopa/benserazide elicits pronounced met- abolic changes in both adipose tissue and skeletal muscle with a switch from lipid to carbohydrate metabolism. In adipose tissue, levodopa/benserazide failed to activate lipolysis. Therefore, we suggest that levodopa/benserazide does not induce fat wasting through direct and acute influences on adipose tissue metabolism. Keywords Parkinson’ s disease . Metabolism . Lipolysis . Adipose tissue . Skeletal muscle Introduction Weight loss due to body-fat wasting is a poorly understood phenomenon in Parkinson’ s disease patients. Whether or not therapy contributes to wasting is unknown [1–3]. Weight loss cannot be solely attributed to severity of motor symptoms [3–7]. In contrast to patients undergoing drug therapy, Parkinson’ s disease patients who are treated with deep brain electrical stimulation often experience substan- tial weight gain [8]. The observation challenges the concept that weight loss in drug-treated patients is explained by augmented energy expenditure through improved motor function [3, 4]. Instead, Parkinson’ s medications may directly affect adipose tissue mobilization [4]. Levodopa in combination with peripheral aromatic l-amino acid decarboxylase inhibitors is still the most common and effective treatment [9]. In the absence of a decarboxylase inhibitor, levodopa increases circulating free fatty acid concentrations [10, 11]. However, the observation is of Eur J Clin Pharmacol (2008) 64:863–870 DOI 10.1007/s00228-008-0532-4 F. Adams : M. Boschmann : G. Franke : M. C. Leisse : J. Janke : S. Gottschalk : J. Jordan Experimental and Clinical Research Center – A Cooperation with Max Delbrueck Center for Molecular Medicine, Charité Campus Buch, and HELIOS Klinikum, Berlin, Germany E. Lobsien : A. Kupsch : A. Lipp Department of Neurology, Charité Campus Virchow, Berlin, Germany J. Spranger German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany F. Adams (*) Franz-Volhard Clinical Research Center, Charité Campus Buch, Lindenberger Weg 80, 13125 Berlin, Germany e-mail: Frauke.Adams@charite.de