Ghrelin mimics fasting to enhance human hedonic, orbitofrontal cortex, and hippocampal responses to food.
BACKGROUND
Ghrelin, which is a stomach-derived hormone, increases with fasting and energy restriction and may influence eating behaviors through brain hedonic reward-cognitive systems. Therefore, changes in plasma ghrelin might mediate counter-regulatory responses to a negative energy balance through changes in food hedonics.


OBJECTIVE
We investigated whether ghrelin administration (exogenous hyperghrelinemia) mimics effects of fasting (endogenous hyperghrelinemia) on the hedonic response and activation of brain-reward systems to food.


METHODS
In a crossover design, 22 healthy, nonobese adults (17 men) underwent a functional magnetic resonance imaging (fMRI) food-picture evaluation task after a 16-h overnight fast (Fasted-Saline) or after eating breakfast 95 min before scanning (730 kcal, 14% protein, 31% fat, and 55% carbohydrate) and receiving a saline (Fed-Saline) or acyl ghrelin (Fed-Ghrelin) subcutaneous injection before scanning. One male subject was excluded from the fMRI analysis because of excess head motion, which left 21 subjects with brain-activation data.


RESULTS
Compared with the Fed-Saline visit, both ghrelin administration to fed subjects (Fed-Ghrelin) and fasting (Fasted-Saline) significantly increased the appeal of high-energy foods and associated orbitofrontal cortex activation. Both fasting and ghrelin administration also increased hippocampus activation to high-energy- and low-energy-food pictures. These similar effects of endogenous and exogenous hyperghrelinemia were not explicable by consistent changes in glucose, insulin, peptide YY, and glucagon-like peptide-1. Neither ghrelin administration nor fasting had any significant effect on nucleus accumbens, caudate, anterior insula, or amygdala activation during the food-evaluation task or on auditory, motor, or visual cortex activation during a control task.


CONCLUSIONS
Ghrelin administration and fasting have similar acute stimulatory effects on hedonic responses and the activation of corticolimbic reward-cognitive systems during food evaluations. Similar effects of recurrent or chronic hyperghrelinemia on an anticipatory food reward may contribute to the negative impact of skipping breakfast on dietary habits and body weight and the long-term failure of energy restriction for weight loss.
From the Metabolic and Molecular Imaging Group (APG, CGP, SS, ADM, NC, SSD, and JDB) and Robert Steiner MRI Unit (GD), Medical Research Council Clinical Sciences Centre, the Computational, Cognitive and Clinical Neuroimaging Laboratory, Division of Brain Sciences (CB), the Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism (MAG, DRA, GSF, and SRB), and the Division of Brain Sciences (ADW), Imperial College London, Hammersmith Hospital, London, United Kingdom, and the Department of Endocrinology, University of Virginia, Charlottesville, VA (BDG and MOT).
Anthony P
AP
Goldstone
From the Metabolic and Molecular Imaging Group (APG, CGP, SS, ADM, NC, SSD, and JDB) and Robert Steiner MRI Unit (GD), Medical Research Council Clinical Sciences Centre, the Computational, Cognitive and Clinical Neuroimaging Laboratory, Division of Brain Sciences (CB), the Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism (MAG, DRA, GSF, and SRB), and the Division of Brain Sciences (ADW), Imperial College London, Hammersmith Hospital, London, United Kingdom, and the Department of Endocrinology, University of Virginia, Charlottesville, VA (BDG and MOT).
Christina G
CG
Prechtl
From the Metabolic and Molecular Imaging Group (APG, CGP, SS, ADM, NC, SSD, and JDB) and Robert Steiner MRI Unit (GD), Medical Research Council Clinical Sciences Centre, the Computational, Cognitive and Clinical Neuroimaging Laboratory, Division of Brain Sciences (CB), the Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism (MAG, DRA, GSF, and SRB), and the Division of Brain Sciences (ADW), Imperial College London, Hammersmith Hospital, London, United Kingdom, and the Department of Endocrinology, University of Virginia, Charlottesville, VA (BDG and MOT).
Samantha
S
Scholtz
From the Metabolic and Molecular Imaging Group (APG, CGP, SS, ADM, NC, SSD, and JDB) and Robert Steiner MRI Unit (GD), Medical Research Council Clinical Sciences Centre, the Computational, Cognitive and Clinical Neuroimaging Laboratory, Division of Brain Sciences (CB), the Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism (MAG, DRA, GSF, and SRB), and the Division of Brain Sciences (ADW), Imperial College London, Hammersmith Hospital, London, United Kingdom, and the Department of Endocrinology, University of Virginia, Charlottesville, VA (BDG and MOT).
Alexander D
AD
Miras
From the Metabolic and Molecular Imaging Group (APG, CGP, SS, ADM, NC, SSD, and JDB) and Robert Steiner MRI Unit (GD), Medical Research Council Clinical Sciences Centre, the Computational, Cognitive and Clinical Neuroimaging Laboratory, Division of Brain Sciences (CB), the Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism (MAG, DRA, GSF, and SRB), and the Division of Brain Sciences (ADW), Imperial College London, Hammersmith Hospital, London, United Kingdom, and the Department of Endocrinology, University of Virginia, Charlottesville, VA (BDG and MOT).
Navpreet
N
Chhina
From the Metabolic and Molecular Imaging Group (APG, CGP, SS, ADM, NC, SSD, and JDB) and Robert Steiner MRI Unit (GD), Medical Research Council Clinical Sciences Centre, the Computational, Cognitive and Clinical Neuroimaging Laboratory, Division of Brain Sciences (CB), the Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism (MAG, DRA, GSF, and SRB), and the Division of Brain Sciences (ADW), Imperial College London, Hammersmith Hospital, London, United Kingdom, and the Department of Endocrinology, University of Virginia, Charlottesville, VA (BDG and MOT).
Giuliana
G
Durighel
From the Metabolic and Molecular Imaging Group (APG, CGP, SS, ADM, NC, SSD, and JDB) and Robert Steiner MRI Unit (GD), Medical Research Council Clinical Sciences Centre, the Computational, Cognitive and Clinical Neuroimaging Laboratory, Division of Brain Sciences (CB), the Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism (MAG, DRA, GSF, and SRB), and the Division of Brain Sciences (ADW), Imperial College London, Hammersmith Hospital, London, United Kingdom, and the Department of Endocrinology, University of Virginia, Charlottesville, VA (BDG and MOT).
Seyedeh S
SS
Deliran
From the Metabolic and Molecular Imaging Group (APG, CGP, SS, ADM, NC, SSD, and JDB) and Robert Steiner MRI Unit (GD), Medical Research Council Clinical Sciences Centre, the Computational, Cognitive and Clinical Neuroimaging Laboratory, Division of Brain Sciences (CB), the Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism (MAG, DRA, GSF, and SRB), and the Division of Brain Sciences (ADW), Imperial College London, Hammersmith Hospital, London, United Kingdom, and the Department of Endocrinology, University of Virginia, Charlottesville, VA (BDG and MOT).
Christian
C
Beckmann
From the Metabolic and Molecular Imaging Group (APG, CGP, SS, ADM, NC, SSD, and JDB) and Robert Steiner MRI Unit (GD), Medical Research Council Clinical Sciences Centre, the Computational, Cognitive and Clinical Neuroimaging Laboratory, Division of Brain Sciences (CB), the Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism (MAG, DRA, GSF, and SRB), and the Division of Brain Sciences (ADW), Imperial College London, Hammersmith Hospital, London, United Kingdom, and the Department of Endocrinology, University of Virginia, Charlottesville, VA (BDG and MOT).
Mohammad A
MA
Ghatei
From the Metabolic and Molecular Imaging Group (APG, CGP, SS, ADM, NC, SSD, and JDB) and Robert Steiner MRI Unit (GD), Medical Research Council Clinical Sciences Centre, the Computational, Cognitive and Clinical Neuroimaging Laboratory, Division of Brain Sciences (CB), the Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism (MAG, DRA, GSF, and SRB), and the Division of Brain Sciences (ADW), Imperial College London, Hammersmith Hospital, London, United Kingdom, and the Department of Endocrinology, University of Virginia, Charlottesville, VA (BDG and MOT).
Damien R
DR
Ashby
From the Metabolic and Molecular Imaging Group (APG, CGP, SS, ADM, NC, SSD, and JDB) and Robert Steiner MRI Unit (GD), Medical Research Council Clinical Sciences Centre, the Computational, Cognitive and Clinical Neuroimaging Laboratory, Division of Brain Sciences (CB), the Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism (MAG, DRA, GSF, and SRB), and the Division of Brain Sciences (ADW), Imperial College London, Hammersmith Hospital, London, United Kingdom, and the Department of Endocrinology, University of Virginia, Charlottesville, VA (BDG and MOT).
Adam D
AD
Waldman
From the Metabolic and Molecular Imaging Group (APG, CGP, SS, ADM, NC, SSD, and JDB) and Robert Steiner MRI Unit (GD), Medical Research Council Clinical Sciences Centre, the Computational, Cognitive and Clinical Neuroimaging Laboratory, Division of Brain Sciences (CB), the Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism (MAG, DRA, GSF, and SRB), and the Division of Brain Sciences (ADW), Imperial College London, Hammersmith Hospital, London, United Kingdom, and the Department of Endocrinology, University of Virginia, Charlottesville, VA (BDG and MOT).
Bruce D
BD
Gaylinn
From the Metabolic and Molecular Imaging Group (APG, CGP, SS, ADM, NC, SSD, and JDB) and Robert Steiner MRI Unit (GD), Medical Research Council Clinical Sciences Centre, the Computational, Cognitive and Clinical Neuroimaging Laboratory, Division of Brain Sciences (CB), the Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism (MAG, DRA, GSF, and SRB), and the Division of Brain Sciences (ADW), Imperial College London, Hammersmith Hospital, London, United Kingdom, and the Department of Endocrinology, University of Virginia, Charlottesville, VA (BDG and MOT).
Michael O
MO
Thorner
From the Metabolic and Molecular Imaging Group (APG, CGP, SS, ADM, NC, SSD, and JDB) and Robert Steiner MRI Unit (GD), Medical Research Council Clinical Sciences Centre, the Computational, Cognitive and Clinical Neuroimaging Laboratory, Division of Brain Sciences (CB), the Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism (MAG, DRA, GSF, and SRB), and the Division of Brain Sciences (ADW), Imperial College London, Hammersmith Hospital, London, United Kingdom, and the Department of Endocrinology, University of Virginia, Charlottesville, VA (BDG and MOT).
Gary S
GS
Frost
From the Metabolic and Molecular Imaging Group (APG, CGP, SS, ADM, NC, SSD, and JDB) and Robert Steiner MRI Unit (GD), Medical Research Council Clinical Sciences Centre, the Computational, Cognitive and Clinical Neuroimaging Laboratory, Division of Brain Sciences (CB), the Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism (MAG, DRA, GSF, and SRB), and the Division of Brain Sciences (ADW), Imperial College London, Hammersmith Hospital, London, United Kingdom, and the Department of Endocrinology, University of Virginia, Charlottesville, VA (BDG and MOT).
Stephen R
SR
Bloom
From the Metabolic and Molecular Imaging Group (APG, CGP, SS, ADM, NC, SSD, and JDB) and Robert Steiner MRI Unit (GD), Medical Research Council Clinical Sciences Centre, the Computational, Cognitive and Clinical Neuroimaging Laboratory, Division of Brain Sciences (CB), the Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism (MAG, DRA, GSF, and SRB), and the Division of Brain Sciences (ADW), Imperial College London, Hammersmith Hospital, London, United Kingdom, and the Department of Endocrinology, University of Virginia, Charlottesville, VA (BDG and MOT).
Jimmy D
JD
Bell
D000005:Abdomen; D000215:Acylation; D000328:Adult; D001069:Appetite Regulation; D062408:Breakfast; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005215:Fasting; D005502:Food; D005518:Food Preferences; D054439:Ghrelin / Q000008:administration & dosage / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D021621:Imaging, Three-Dimensional; D007279:Injections, Subcutaneous; D008279:Magnetic Resonance Imaging; D008297:Male; D019518:Postprandial Period; D017397:Prefrontal Cortex / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000378:metabolism*; D016037:Single-Blind Method; D055815:Young Adult
C515349:GHRL protein, human; D054439:Ghrelin