title: Functional magnetic resonance imaging analysis of food-related brain activity in patients with lipodystrophy undergoing leptin replacement therapy.
abstract: BACKGROUND
  Lipodystrophy is a disease characterized by a paucity of adipose tissue and low circulating concentrations of adipocyte-derived leptin. Leptin-replacement therapy improves eating and metabolic disorders in patients with lipodystrophy.
  
  
  OBJECTIVE
  The aim of the study was to clarify the pathogenic mechanism of eating disorders in lipodystrophic patients and the action mechanism of leptin on appetite regulation.
  
  
  METHODS
  We investigated food-related neural activity using functional magnetic resonance imaging in lipodystrophic patients with or without leptin replacement therapy and in healthy controls. We also measured the subjective feelings of appetite.
  
  
  RESULTS
  Although there was little difference in the enhancement of neural activity by food stimuli between patients and controls under fasting, postprandial suppression of neural activity was insufficient in many regions of interest including amygdala, insula, nucleus accumbens, caudate, putamen, and globus pallidus in patients when compared with controls. Leptin treatment effectively suppressed postprandial neural activity in many of these regions of interest, whereas it showed little effect under fasting in patients. Consistent with these results, postprandial formation of satiety feeling was insufficient in patients when compared with controls, which was effectively reinforced by leptin treatment.
  
  
  CONCLUSIONS
  This study demonstrated the insufficiency of postprandial suppression of food-related neural activity and formation of satiety feeling in lipodystrophic patients, which was effectively restored by leptin. The findings in this study emphasize the important pathological role of leptin in eating disorders in lipodystrophy and provide a clue to understanding the action mechanism of leptin in human, which may lead to development of novel strategies for prevention and treatment of obesity.
authors.affiliation: Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, and Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Aotani
authors.forename: Ken
authors.initials: K
authors.lastname: Ebihara
authors.forename: Nobukatsu
authors.initials: N
authors.lastname: Sawamoto
authors.forename: Toru
authors.initials: T
authors.lastname: Kusakabe
authors.forename: Megumi
authors.initials: M
authors.lastname: Aizawa-Abe
authors.forename: Sachiko
authors.initials: S
authors.lastname: Kataoka
authors.forename: Takeru
authors.initials: T
authors.lastname: Sakai
authors.forename: Hitomi
authors.initials: H
authors.lastname: Iogawa
authors.forename: Chihiro
authors.initials: C
authors.lastname: Ebihara
authors.forename: Junji
authors.initials: J
authors.lastname: Fujikura
authors.forename: Kiminori
authors.initials: K
authors.lastname: Hosoda
authors.forename: Hidenao
authors.initials: H
authors.lastname: Fukuyama
authors.forename: Kazuwa
authors.initials: K
authors.lastname: Nakao
mesh_terms: D000328:Adult; D000679:Amygdala / Q000502:physiology; D001066:Appetite / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000502:physiology; D003342:Corpus Striatum / Q000502:physiology; D004435:Eating / Q000187:drug effects / Q000502:physiology; D005215:Fasting / Q000502:physiology; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D020738:Leptin / Q000008:administration & dosage* / Q000172:deficiency / Q000502:physiology*; D008060:Lipodystrophy / Q000188:drug therapy* / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D009714:Nucleus Accumbens / Q000502:physiology; D019518:Postprandial Period / Q000502:physiology; D012528:Satiety Response / Q000187:drug effects* / Q000502:physiology*; D055815:Young Adult
chemical_list: D020738:Leptin