title: Leptin is associated with exaggerated brain reward and emotion responses to food images in adolescent obesity.
abstract: OBJECTIVE
  In the U.S., an astonishing 12.5 million children and adolescents are now obese, predisposing 17% of our nation's youth to metabolic complications of obesity, such as type 2 diabetes (T2D). Adolescent obesity has tripled over the last three decades in the setting of food advertising directed at children. Obese adults exhibit increased brain responses to food images in motivation-reward pathways. These neural alterations may be attributed to obesity-related metabolic changes, which promote food craving and high-calorie food (HCF) consumption. It is not known whether these metabolic changes affect neural responses in the adolescent brain during a crucial period for establishing healthy eating behaviors.
  
  
  METHODS
  Twenty-five obese (BMI 34.4 kg/m2, age 15.7 years) and fifteen lean (BMI 20.96 kg/m2, age 15.5 years) adolescents underwent functional MRI during exposure to HCF, low-calorie food (LCF), and nonfood (NF) visual stimuli 2 h after isocaloric meal consumption.
  
  
  RESULTS
  Brain responses to HCF relative to NF cues increased in obese versus lean adolescents in striatal-limbic regions (i.e., putamen/caudate, insula, amygdala) (P < 0.05, family-wise error [FWE]), involved in motivation-reward and emotion processing. Higher endogenous leptin levels correlated with increased neural activation to HCF images in all subjects (P < 0.05, FWE).
  
  
  CONCLUSIONS
  This significant association between higher circulating leptin and hyperresponsiveness of brain motivation-reward regions to HCF images suggests that dysfunctional leptin signaling may contribute to the risk of overconsumption of these foods, thus further predisposing adolescents to the development of obesity and T2D.
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT Division of Pediatric Endocrinology, Department of Pediatrics, Yale University School of Medicine, New Haven, CT.
authors.forename: Ania M
authors.initials: AM
authors.lastname: Jastreboff
authors.affiliation: Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Lacadie
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, Yale Stress Center, New Haven, CT.
authors.forename: Dongju
authors.initials: D
authors.lastname: Seo
authors.affiliation: Division of Pediatric Endocrinology, Department of Pediatrics, Yale University School of Medicine, New Haven, CT.
authors.forename: Jessica
authors.initials: J
authors.lastname: Kubat
authors.affiliation: Division of Pediatric Endocrinology, Department of Pediatrics, Yale University School of Medicine, New Haven, CT.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Van Name
authors.affiliation: Department of Pediatric, University of Chieti, Chieti, Italy.
authors.forename: Cosimo
authors.initials: C
authors.lastname: Giannini
authors.affiliation: Division of Pediatric Endocrinology, Department of Pediatrics, Yale University School of Medicine, New Haven, CT.
authors.forename: Mary
authors.initials: M
authors.lastname: Savoye
authors.affiliation: Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT.
authors.forename: R Todd
authors.initials: RT
authors.lastname: Constable
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Sherwin
authors.affiliation: Division of Pediatric Endocrinology, Department of Pediatrics, Yale University School of Medicine, New Haven, CT sonia.caprio@yale.edu rajita.sinha@yale.edu.
authors.forename: Sonia
authors.initials: S
authors.lastname: Caprio
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, Yale Stress Center, New Haven, CT Department of Neurobiology, Yale University School of Medicine, New Haven, CT Child Study Center, Yale University School of Medicine, New Haven, CT sonia.caprio@yale.edu rajita.sinha@yale.edu.
authors.forename: Rajita
authors.initials: R
authors.lastname: Sinha
mesh_terms: D000293:Adolescent; D001921:Brain / Q000378:metabolism*; D001931:Brain Mapping; D016022:Case-Control Studies; D002648:Child; D003463:Cues; D004644:Emotions; D005260:Female; D005502:Food; D006801:Humans; D020738:Leptin / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D009042:Motivation; D063766:Pediatric Obesity / Q000523:psychology*; D012201:Reward
chemical_list: D020738:Leptin