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Free keywords:
Metreleptin; Leptin; Lipodystrophy; Neuroimaging; Brain connectivity; Hypothalamus
Abstract:
Context
Research in lipodystrophy (LD) and its treatment with metreleptin has not only helped LD patients, but has opened new directions in investigating leptin’s role in metabolism and the regulation of eating behavior. Previously, in a study with LD patients undergoing metreleptin treatment using functional magnetic resonance imaging (MRI), we found significantly increased resting-state brain connectivity in three 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 four female LD patients undergoing metreleptin treatment and three healthy untreated controls were performed at four different time points over twelve 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 LD patients, we found a significant brain connectivity increase in the hypothalamus and bilaterally in posterior cingulate gyrus. Using a three-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 LD patients, 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 building a foundation for further research of central nervous effects of this important metabolic hormone.
