Functional neuroimaging demonstrates that ghrelin inhibits the central nervous system response to ingested lipid.
OBJECTIVE
Gut-derived humoural factors activate central nervous system (CNS) mechanisms controlling energy intake and expenditure, and autonomic outflow. Ghrelin is secreted from the stomach and stimulates food intake and gastric emptying, but the relevant mechanisms are poorly understood. Nutrient-activated CNS systems can be studied in humans by physiological/pharmacological MRI (phMRI). This method has been used to examine the CNS responses to exogenous ghrelin.


METHODS
phMRI was used to study the CNS responses in healthy people to a ghrelin bolus (0.3 nmol/kg, intravenous) in the post-prandial state, and an intravenous infusion of ghrelin (1.25 pmol/kg/min) alone and after intragastric lipid (dodecanoate, C12) in people who have fasted.


RESULTS
A ghrelin bolus decreased the blood oxygenation level dependent (BOLD) signal detected by phMRI in feeding-activated areas of the CNS in the post-prandial state. Infusion of ghrelin reversed the effect of C12 in delaying gastric emptying but had no effect on hunger. Intragastric C12 caused strong bilateral activation of a matrix of CNS areas, including the brain stem, hypothalamus and limbic areas which was attenuated by exogenous ghrelin. Ghrelin infusion alone had a small but significant stimulatory effect on CNS BOLD signals.


CONCLUSIONS
Ghrelin inhibits activation of the hypothalamus and brain stem induced by ingested nutrients, suggesting a role in suppression of gut-derived satiety signals in humans.
Gastrointestinal Sciences, Clinical Sciences Building, Manchester Academic Health Sciences Centre (MAHSC), University of Manchester, Salford, UK.
Richard B
RB
Jones
Shane
S
McKie
Nerys
N
Astbury
Tanya J
TJ
Little
Stacey
S
Tivey
Daniel J
DJ
Lassman
John
J
McLaughlin
Simon
S
Luckman
Steve R
SR
Williams
Graham J
GJ
Dockray
David G
DG
Thompson
D000328:Adult; D015992:Body Mass Index; D002490:Central Nervous System / Q000187:drug effects / Q000502:physiology*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects / Q000502:physiology; D005260:Female; D059907:Functional Neuroimaging; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology; D054439:Ghrelin / Q000008:administration & dosage / Q000378:metabolism*; D006801:Humans; D006815:Hunger / Q000187:drug effects / Q000502:physiology; D007262:Infusions, Intravenous; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology*; D008055:Lipids / Q000008:administration & dosage; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D012680:Sensitivity and Specificity; D055815:Young Adult
D054439:Ghrelin; D008055:Lipids