Leptin Regulates Striatal Regions and Human Eating Behavior
Open accessAbstract
Studies of the fat-derived hormone leptin have provided key insights into the molecular and neural components of feeding behavior and body weight regulation. An important challenge lies in understanding how the rewarding properties of food interact with, and can override, physiological satiety signals and promote overeating. We used functional magnetic resonance imaging to measure brain responses in two human patients with congenital leptin deficiency who were shown images of food before and after 7 days of leptin replacement therapy. Leptin was found to modulate neural activation in key striatal regions, suggesting that the hormone acts on neural circuits governing food intake to diminish the perception of food reward while enhancing the response to satiety signals generated during food consumption.
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After leptin treatment in leptin-deficient patients and in normal subjects, nucleus accumbens activation is only correlated with ratings of liking in the fasted state.
“After leptin treatment in these leptin-deficient patients, and in normal subjects, nucleus accumbens activation was only correlated with ratings of liking in the fasted state”
From Food reward, hyperphagia, and obesity (2011) · cites this paper as [57]
Neural activation in the nucleus accumbens elicited by visual food stimuli is very high in genetically leptin-deficient adolescents and promptly returns to normal levels upon leptin administration.
“Neural activation in the nucleus accumbens elicited by visual food stimuli is very high in genetically leptin-deficient adolescents and promptly returns to normal levels upon leptin administration”
From Food reward, hyperphagia, and obesity (2011) · cites this paper as [57]
Foods considered bland under normal conditions were liked very much in the absence of leptin signaling.
“Even foods considered bland under normal conditions (with leptin in the satiated state) were liked very much in the absence of leptin signaling.”
From Food reward, hyperphagia, and obesity (2011) · cites this paper as [57]
In the leptin-deficient state, nucleus accumbens activation is positively correlated with ratings of liking for the food shown in images in both the fasted and fed state.
“In the leptin-deficient state, nucleus accumbens activation was positively correlated with ratings of liking for the food shown in images in both the fasted and fed state.”
From Food reward, hyperphagia, and obesity (2011) · cites this paper as [57]
In genetically leptin-deficient humans, neural activity in the nucleus accumbens elicited by viewing pictures of palatable foods was exaggerated in the absence of leptin and abolished after leptin administration.
“However, in genetically leptin-deficient humans, neural activity in the nucleus accumbens elicited by viewing pictures of palatable foods was exaggerated in the absence of leptin and abolished after leptin administration ([57](#B57)).”
From Food reward, hyperphagia, and obesity (2011) · cites this paper as [57]
In leptin-deficient subjects, functional magnetic resonance imaging reveals a marked increase in activity in the nucleus accumbens in response to images of food even after eating.
“Consistent with this, functional magnetic resonance imaging of leptin-deficient subjects has revealed a marked increase in activity in the nucleus accumbens in response to images of food even after eating (52)(53)(54).”
From Leptin at 14 y of age: an ongoing story (2009) · cites this paper as [52]
Leptin therapy normalizes the increased accumbens activity after eating in leptin-deficient patients.
“The activity that is seen in the accumbens in leptin-deficient patients after eating was normalized by the use of leptin therapy (52)(53)(54).”
From Leptin at 14 y of age: an ongoing story (2009) · cites this paper as [52]
Leptin-deficient patients show markedly different food preferences and perception of food than do normal individuals.
“In addition, leptin-deficient patients show markedly different food preferences and perception of food than do normal individuals (52)(53)(54).”
From Leptin at 14 y of age: an ongoing story (2009) · cites this paper as [52]
Normal individuals typically show this activity only in the starved state and do not show this response after eating.
“Normal individuals typically show this activity only in the starved state and do not show this response after eating.”
From Leptin at 14 y of age: an ongoing story (2009) · cites this paper as [52]
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- Authors
- Farooqi, I. S., Bullmore, E., Keogh, J., Gillard, J., O'Rahilly, S., & Fletcher, P. C.
- Affiliations
- University of Cambridge (GB)
- University Department of Medicine and Department of Clinical Biochemistry, Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 2QQ, UK.
- Corresponding author
- Farooqi, I. Sadaf
- Fletcher, Paul C.
- Venue
- Science
- Published
- 2007-09-07
- Volume
- 317
- Issue
- 5843
- Pages
- 1355-1355
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC3838941
- OpenAlex
- W1969621876
- Cited by
- 622
- References
- 4
- Citations by year
- 2026: 5 · 2025: 16 · 2024: 20 · 2023: 24 · 2022: 23 · 2021: 42 · 2020: 37 · 2019: 25 · 2018: 28 · 2017: 34 · 2016: 28 · 2015: 44 · 2014: 38 · 2013: 35 · 2012: 59
- FWCI
- 15.77
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Wellcome Trust (068086, 064351)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Social Sciences › Psychology › Clinical Psychology › Eating Disorders and Behaviors
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- leptin, congenital leptin deficiency, leptin replacement therapy, striatum, food reward, satiety signals, dietary habits, food intake regulation, body weight regulation
- MeSH terms
- Adolescent, Adult, Brain Mapping, Corpus Striatum, Eating, Feeding Behavior, Female, Humans, Magnetic Resonance Imaging, Male, Nucleus Accumbens, Satiation, Visual Perception, Leptin
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