title: Leptin Substitution in Patients With Lipodystrophy: Neural Correlates for Long-term Success in the Normalization of Eating Behavior.
abstract: Lipodystrophy (LD) is a rare disease with a paucity of subcutaneous adipocytes and leptin deficiency. Patients often develop severe diabetes and, additionally, show a disturbed eating behavior with reduced satiety. The disturbed eating behavior can be restored by substitution with the leptin analog metreleptin. Long-term effects of metreleptin on resting state brain connectivity in treatment-naive patients with LD have not been assessed. In this study, resting state functional MRI scans and extensive behavioral testing assessing changes in hunger/satiety regulation were performed during the first 52 weeks of metreleptin treatment in nine patients with LD. Resting state connectivity significantly increased over the course of metreleptin treatment in three brain areas (i.e., hypothalamus, insula/superior temporal gyrus, medial prefrontal cortex). Behavioral tests demonstrated that perceived hunger, importance of eating, eating frequencies, and liking ratings of food pictures significantly decreased during metreleptin therapy. Taken together, leptin substitution was accompanied by long-term changes of hedonic and homeostatic central nervous networks regulating eating behavior as well as decreased hunger feelings and diminished incentive value of food. Future studies need to assess whether metreleptin treatment in LD restores physiological processes important for the development of satiety.
authors.affiliation: Department of Medicine, University Hospital Leipzig, Leipzig, Germany haiko.schloegl@medizin.uni-leipzig.de.
authors.forename: Haiko
authors.initials: H
authors.lastname: Schlögl
authors.affiliation: Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Müller
authors.affiliation: Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany Integrated Research and Treatment Center AdiposityDiseases, University of Leipzig, Leipzig, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Horstmann
authors.affiliation: Department of Medicine, University Hospital Leipzig, Leipzig, Germany.
authors.forename: Konstanze
authors.initials: K
authors.lastname: Miehle
authors.affiliation: Department of Medicine, University Hospital Leipzig, Leipzig, Germany Integrated Research and Treatment Center AdiposityDiseases, University of Leipzig, Leipzig, Germany.
authors.forename: Janett
authors.initials: J
authors.lastname: Püschel
authors.affiliation: Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany Day Clinic of Cognitive Neurology, University of Leipzig, Leipzig, Germany.
authors.forename: Arno
authors.initials: A
authors.lastname: Villringer
authors.affiliation: Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany Department of Neurology, BG University Clinic Bergmannsheil, Ruhr University Bochum, Bochum, Germany.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Pleger
authors.affiliation: Department of Medicine, University Hospital Leipzig, Leipzig, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Stumvoll
authors.affiliation: Department of Medicine, University Hospital Leipzig, Leipzig, Germany Integrated Research and Treatment Center AdiposityDiseases, University of Leipzig, Leipzig, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Fasshauer
mesh_terms: D000328:Adult; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D005247:Feeding Behavior / Q000187:drug effects*; D005260:Female; D006801:Humans; D006815:Hunger / Q000187:drug effects; D020738:Leptin / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use*; D008060:Lipodystrophy / Q000188:drug therapy* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D012527:Satiation / Q000187:drug effects
chemical_list: D020738:Leptin; C415771:metreleptin