Leptin is associated with exaggerated brain reward and emotion responses to food images in adolescent obesity
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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.
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Appetitive brain areas such as the striatum, insula, and orbitofrontal cortex that are commonly activated by viewing rewarding and energy-dense food pictures are significantly reduced by GLP-1 RA.
“Appetitive brain areas such as the striatum, insula, and orbitofrontal cortex that are commonly activated by viewing rewarding and energy-dense food pictures (13) are also significantly reduced by GLP-1 RA (14).”
From New Frontiers in Obesity Treatment: GLP-1 and Nascent Nutrient-Stimulated Hormone-Based Therapeutics (2023) · cites this paper as [13]
Higher leptin levels associated with obesity predicted blunted ventromedial prefrontal cortex and rostral anterior cingulate activation to high-fat food images and to glucose and fructose intake in adolescents.
“higher leptin levels (associated with obesity) predicted blunted ventromedial prefrontal cortex and rostral anterior cingulate (VmPFC/rACC) activation to high fat food images and to glucose and fructose intake in adolescents”
From Role of addiction and stress neurobiology on food intake and obesity (2018) · cites this paper as Jastreboff et al., 2014
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Structural and Functional Brain Changes in Children and Adolescents With Obesity
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- Authors
- Jastreboff, A. M., Lacadie, C., Seo, D., Kubat, J., Van Name, M. A., Giannini, C., Savoye, M., Constable, R. T., Sherwin, R. S., Caprio, S., & Sinha, R.
- Affiliations
- Yale University (US)
- Division of Pediatric Endocrinology, Department of Pediatrics, Yale University School of Medicine, New Haven, CT
- University of Chieti-Pescara (IT)
- Corresponding author
- Caprio, Sonia
- Sinha, Rajita
- ORCID
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2014-10-10
- Volume
- 37
- Issue
- 11
- Pages
- 3061-3068
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- PMC
- PMC4207200
- OpenAlex
- W2166828561
- Cited by
- 83
- References
- 54
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 5 · 2023: 9 · 2022: 3 · 2021: 13 · 2020: 11 · 2019: 8 · 2018: 7 · 2017: 11 · 2016: 5 · 2015: 2 · 2014: 2
- FWCI
- 3.25
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Diabetes Care (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (UL1TR000142)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK020495, R01DK099039, R37 DK 20495, K12DK094714, K23DK101694, R37DK020495, R01DK085577, P30DK045735)
- National Institute of Dental and Craniofacial Research (UL1DE019586)
- National Center for Research Resources (UL1RR024139)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Social Sciences › Psychology › Clinical Psychology › Eating Disorders and Behaviors
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- leptin, adolescent obesity, food images, high-calorie foods, amygdala, insula, caudate nucleus, putamen, food cravings, type 2 diabetes risk, leptin signaling
- MeSH terms
- Adolescent, Brain, Brain Mapping, Child, Cues, Emotions, Female, Food, Humans, Magnetic Resonance Imaging, Male, Motivation, Reward, Case-Control Studies, Leptin, Pediatric Obesity
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