title: Effects of leptin deficiency and replacement on cerebellar response to food-related cues.
abstract: Leptin affects eating behavior partly by altering the response of the brain to food-related stimuli. The effects of leptin on brain structure have been observed in the cerebellum, where leptin receptors are most densely expressed, but the function of leptin in the cerebellum remains unclear. We performed a nonrandomized, prospective interventional study of three adults with genetically mediated leptin deficiency. FMRI was recorded three times each year during years 5 and 6 of leptin replacement treatment. Session 1 of each year occurred after 10 months of continuous daily replacement, session 2 after 33-37 days without leptin, and session 3 at 14-23 days after daily replacement was restored. Statistical parametric mapping software (SPM5) was employed to contrast the fMRI blood oxygenation level-dependent response to images of high-calorie foods versus images of brick walls. Covariate analyses quantified the effects of the duration of leptin replacement and concomitant changes in body mass on the cerebral responses. Longer duration of replacement was associated with more activation by food images in a ventral portion of the posterior lobe of the cerebellum, while simultaneous decreases in body mass were associated with decreased activation in a more dorsal portion of the same lobe. These findings indicate that leptin replacement reversibly alters neural function within the posterior cerebellum and modulates plasticity-dependent brain physiology in response to food cues. The results suggest an underexplored role for the posterior cerebellum in the regulation of leptin-mediated processes related to food intake.
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences and the Semel Institute, David Geffen School of Medicine, University of California Los Angeles, 760 Westwood Plaza, C8-831, Los Angeles, CA 90024, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Berman
authors.forename: Gilberto
authors.initials: G
authors.lastname: Paz-Filho
authors.forename: Ma-Li
authors.initials: ML
authors.lastname: Wong
authors.forename: Milky
authors.initials: M
authors.lastname: Kohno
authors.forename: Julio
authors.initials: J
authors.lastname: Licinio
authors.forename: Edythe D
authors.initials: ED
authors.lastname: London
mesh_terms: D000328:Adult; D001069:Appetite Regulation / Q000187:drug effects / Q000502:physiology; D015992:Body Mass Index; D002531:Cerebellum / Q000187:drug effects* / Q000502:physiology; D003463:Cues; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D002149:Energy Intake / Q000187:drug effects / Q000502:physiology; D005260:Female; D020249:Hormone Replacement Therapy / Q000379:methods*; D006801:Humans; D020738:Leptin / Q000008:administration & dosage* / Q000172:deficiency* / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009765:Obesity / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D020738:Leptin