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.

Research design and 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.

Trial registration: ClinicalTrials.gov NCT01808846.

© 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Figures

Figure 1

Visual food (picture) task procedure during fMRI. A series of 126 pictures (42 HCF, e.g., ice cream, pizza; 42 LCF, e.g., salads, fruits; and 42 NF, e.g., book, bicycle) was presented in random trials across six runs during the fMRI session, with each run consisting of 21 trials (7 trials per each condition).

Figure 2

Neural response differences in cue condition contrasts. Axial brain slices of neural activation differences in HCF versus NF in obese (A), lean (B), and obese compared with lean (C) adolescents (threshold of P < 0.05, FWE corrected). Obese versus lean individuals show increased activation in the amygdala, ventral striatum, hypothalamus, thalamus, caudate, putamen, and insula. The color scale provides t values of the functional activity. Talairach z levels indicated. IFG, inferior frontal gyrus; IPL, inferior parietal lobe; L, left; R, right.

Figure 3

Whole-brain, voxel-based correlation analyses with leptin. Scatterplot shows the correlation between neural activation (β-weights) (HCF vs. NF) and fasting leptin in all subjects in ROIs and brain maps of correlation regions: amygdala (A), hypothalamus (B), hippocampus/parahippocampus (C), posterior insula (D), striatum (E), and angular gyrus (F) (P < 0.05, FWE corrected). β-Weight values are depicted on the x-axis.