title: Leptin therapy alters appetite and neural responses to food stimuli in brain areas of leptin-sensitive subjects without altering brain structure.
abstract: BACKGROUND
  Leptin is a key regulator of energy intake and expenditure. Individuals with congenital leptin deficiency demonstrate structural and functional brain changes when given leptin. However, whether acquired leptin deficiency may operate similarly is unclear.
  
  
  OBJECTIVE
  We set out to determine whether the brains of individuals with acquired leptin deficiency may react to leptin in a similar manner.
  
  
  METHODS
  We used functional magnetic resonance imaging before and after short- and long-term metreleptin treatment in three leptin-sensitive patients with acquired hypoleptinemia. Nine healthy women were scanned as normoleptinemic controls.
  
  
  METHODS
  The setting was an academic medical center.
  
  
  METHODS
  The participants were 3 hypoleptinemic women and nine normoleptinemic, matched women.
  
  
  METHODS
  We used metreleptin, recombinant leptin, therapy for 24 weeks in hypoleptinemic women only.
  
  
  METHODS
  We measured neural changes in response to viewing food as compared to nonfood images. We hypothesized that metreleptin treatment would increase brain activity in areas related to cognitive control and inhibition and would decrease brain activity in areas related to reward processing, as compared to the normoleptinemic counterparts.
  
  
  RESULTS
  Unlike patients with congenital leptin deficiency, hypoleptinemic patients demonstrated no structural brain differences from healthy controls and/or structural changes in response to treatment. Short-term metreleptin treatment in leptin-sensitive hypoleptinemic subjects enhances areas involved in detecting the salience and rewarding value of food during fasting, whereas long-term treatment decreases attention to food and the rewarding value of food after feeding. Furthermore, hypothalamic activity is modulated by metreleptin treatment, and leptin decreases functional connectivity of the hypothalamus to key feeding-related areas in these hypoleptinemic subjects.
  
  
  CONCLUSIONS
  Leptin replacement in acutely hypoleptinemic women did not alter brain structure but did alter functional cortical activity to food cues in key feeding and reward-related areas.
authors.affiliation: Division of Endocrinology (O.M.F., C.F., P.P., M.B., F.Z., C.S.M.), VA Boston Healthcare System and Beth-Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts 02215; Department of Anatomy and Neurobiology (B.-B.K.), Boston University School of Medicine, Boston, Massachusetts 02215; and Division of Radiology (R.R.), Beth-Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts 02215.
authors.forename: Olivia M
authors.initials: OM
authors.lastname: Farr
authors.forename: Christina
authors.initials: C
authors.lastname: Fiorenza
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Papageorgiou
authors.forename: Mary
authors.initials: M
authors.lastname: Brinkoetter
authors.forename: Florencia
authors.initials: F
authors.lastname: Ziemke
authors.forename: Bang-Bon
authors.initials: BB
authors.lastname: Koo
authors.forename: Rafael
authors.initials: R
authors.lastname: Rojas
authors.forename: Christos S
authors.initials: CS
authors.lastname: Mantzoros
mesh_terms: D000293:Adolescent; D000328:Adult; D001066:Appetite / Q000187:drug effects*; D001921:Brain / Q000187:drug effects*; D004435:Eating / Q000187:drug effects* / Q000523:psychology*; D005260:Female; D005502:Food; D020249:Hormone Replacement Therapy; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects; D007266:Inhibition, Psychological; D020738:Leptin / Q000031:analogs & derivatives* / Q000097:blood / Q000172:deficiency* / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D010775:Photic Stimulation; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D020738:Leptin; C415771:metreleptin