Functional neuroimaging demonstrates that ghrelin inhibits the central nervous system response to ingested lipid
- Richard B Jones1,
- Shane McKie2,
- Nerys Astbury1,
- Tanya J Little1,
- Stacey Tivey1,
- Daniel J Lassman1,
- John McLaughlin1,
- Simon Luckman3,
- Steve R Williams4,
- Graham J Dockray5,
- David G Thompson1
- 1Gastrointestinal Sciences, University of Manchester, Hope Hospital, Salford, UK
- 2Neuroscience and Psychiatry Unit, University of Manchester, UK
- 3Life Sciences, University of Manchester, UK
- 4Imaging Science and Biomedical Engineering, University of Manchester, Manchester, UK
- 5Physiological Laboratory, University of Liverpool, Liverpool, UK
- Correspondence to Professor David G Thompson, Gastrointestinal Sciences, Clinical Sciences Building, Manchester Academic Health Sciences Centre (MAHSC), University of Manchester, Salford, UK; david.thompson{at}manchester.ac.uk
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Contributors RBJ and SMc are co-first authors. RBJ: performed studies and wrote article; SMc: performed pilot studies, designed study, analysed data and wrote article; NA: performed study; TJL: designed and performed study; ST: performed study; DJL: performed study; JM: analysed data; SL: designed study; SW: interpreted data, edited article; GJD: wrote grant, contributed to data analysis and wrote article; DGT: co-wrote grant, supervised project, contributed to data analysis and wrote article.
- Revised 28 November 2011
- Accepted 11 December 2011
- Published Online First 7 February 2012
Abstract
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.
Design 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.
Conclusion 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.
- Ghrelin
- fatty acid
- physiological/pharmacological functional magnetic resonance imaging
- CNS
- CCK
- magnetic resonance imaging
- dietary factors
- gastric physiology
- gastrointestinal endocrinology
- gastrointestinal motility
- gastrointestinal regulatory peptides
- gastrointestinal hormones
- tight junction
- gut hormones
- gastrointestinal physiology
- lipid absorption
- gastrointestinal motility
- irritable bowel syndrome
- lipids
- nutrition
- appetite
- abdominal MRI
- nuclear magnetic resonance
- cholecystokinin
- gastrin
- brain/gut interaction
Footnotes
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Funding Supported by grants from the Biotechnology and Biosciences Research Council. TJL was supported by a NHMRC Overseas Clinical Research Postdoctoral Training Fellowship.
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Competing interests None.
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Patient consent The study involved normal healthy human volunteers; patients were not involved. The subjects signed a consent form.
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Ethics approval Salford and Trafford Research and Ethics Committee.
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Provenance and peer review Not commissioned; externally peer reviewed.
