CONTEXT: Research in lipodystrophy (LD) and its treatment with metreleptin has not only helped patients with LD but has opened new directions in investigating leptin's role in metabolism and the regulation of eating behavior. Previously, in a study with patients with LD undergoing metreleptin treatment using functional magnetic resonance imaging (MRI), we found significantly increased resting-state brain connectivity in 3 brain areas including the hypothalamus. OBJECTIVE: In this study, we aimed to reproduce our functional MRI findings in an independent sample and compare results to healthy participants. DESIGN: Measurements in 4 female patients with LD undergoing metreleptin treatment and 3 healthy untreated controls were performed at 4 different time points over 12 weeks. To identify treatment-related brain connectivity alterations, eigenvector centrality was computed from resting-state functional MRI data for each patient and each session. Thereafter, analysis aimed at detecting consistent brain connectivity changes over time across all patients. RESULTS: In parallel to metreleptin treatment of the patients with LD, we found a significant brain connectivity increase in the hypothalamus and bilaterally in posterior cingulate gyrus. Using a 3-factorial model, a significant interaction between group and time was found in the hypothalamus. CONCLUSIONS: Investigating brain connectivity alterations with metreleptin treatment using an independent sample of patients with LD, we have reproduced an increase of brain connectivity in hedonic and homeostatic central nervous networks observed previously with metreleptin treatment. These results are an important contribution to ascertain brain leptin action and help build a foundation for further research of central nervous effects of this important metabolic hormone.

Day Clinic of Cognitive Neurology University of Leipzig 04103 Leipzig Germany

Department of Endocrinology Nephrology Rheumatology Division of Endocrinology University Hospital Leipzig 04103 Leipzig Germany

Department of Neurology Charles University 1st Faculty of Medicine and General University Hospital 120 00 Prague Czech Republic

Helmholtz Institute for Metabolic Obesity and Vascular Research of the Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig 04103 Leipzig Germany

Institute of Nutritional Sciences Justus Liebig University 35392 Giessen Germany

Max Planck Institute for Human Cognitive and Brain Sciences 04103 Leipzig Germany

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Metreleptin Robustly Increases Resting-state Brain Connectivity in Treatment-naïve Female Patients With Lipodystrophy