title: The neural signature of satiation is associated with ghrelin response and triglyceride metabolism.
abstract: Eating behavior is guided by a complex interaction between signals conveying information about energy stores, food availability, and palatability. How peripheral signals regulate brain circuits that guide feeding during sensation and consumption of a palatable food is poorly understood. We used fMRI to measure brain response to a palatable food (milkshake) when n=32 participants were fasted and fed with either a fixed-portion or ad libitum meal. We found that larger post-prandial reductions in ghrelin and increases in triglycerides were associated with greater attenuation of response to the milkshake in brain regions regulating reward and feeding including the midbrain, amygdala, pallidum, hippocampus, insula and medial orbitofrontal cortex. Satiation-induced brain responses to milkshake were not related to acute changes in circulating insulin, glucose, or free fatty acids. The impact of a meal on the response to milkshake in the midbrain and dorsolateral prefrontal cortex differed depending upon whether meal termination was fixed or volitional, irrespective of the amount of food consumed. We conclude that satiation-induced changes in brain response to a palatable food are strongly and specifically associated with changes in circulating ghrelin and triglycerides and by volitional meal termination.
authors.affiliation: Yale Interdepartmental Neuroscience Program, Yale Medical School, New Haven, CT, USA; John B. Pierce Laboratory, 290 Congress Avenue, New Haven, CT, USA. Electronic address: xue.sun@yale.edu.
authors.forename: Xue
authors.initials: X
authors.lastname: Sun
authors.affiliation: John B. Pierce Laboratory, 290 Congress Avenue, New Haven, CT, USA; Department of Psychiatry, Yale Medical School, New Haven, CT, USA.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Veldhuizen
authors.affiliation: John B. Pierce Laboratory, 290 Congress Avenue, New Haven, CT, USA.
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Wray
authors.affiliation: John B. Pierce Laboratory, 290 Congress Avenue, New Haven, CT, USA; Department of Psychiatry, Yale Medical School, New Haven, CT, USA.
authors.forename: Ivan E
authors.initials: IE
authors.lastname: de Araujo
authors.affiliation: Department of Internal Medicine, Yale Medical School, New Haven, CT, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Sherwin
authors.affiliation: Department of Psychiatry, Yale Medical School, New Haven, CT, USA.
authors.forename: Rajita
authors.initials: R
authors.lastname: Sinha
authors.affiliation: Yale Interdepartmental Neuroscience Program, Yale Medical School, New Haven, CT, USA; John B. Pierce Laboratory, 290 Congress Avenue, New Haven, CT, USA; Department of Psychiatry, Yale Medical School, New Haven, CT, USA; Department of Psychology, Yale University, New Haven, CT, USA; Center for Excellence, University of Cologne, Cologne, Germany; Max-Planck Institute for Neurological Research, Cologne, Germany. Electronic address: dsmall@jbpierce.org.
authors.forename: Dana M
authors.initials: DM
authors.lastname: Small
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D001931:Brain Mapping; D004435:Eating / Q000502:physiology / Q000523:psychology*; D005215:Fasting; D005260:Female; D054439:Ghrelin / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D010100:Oxygen / Q000097:blood; D012527:Satiation; D013649:Taste / Q000502:physiology; D014280:Triglycerides / Q000378:metabolism*; D055815:Young Adult
chemical_list: D054439:Ghrelin; D014280:Triglycerides; D010100:Oxygen
keywords: Feeding; Ghrelin; Gut-brain axis; Satiation; Satiety; Triglycerides; fMRI
references.citation: Science. 1971 Sep 17;173(4002):1103-7
references.pmid: 5098954
references.citation: Neuroimage. 2009 Feb 1;44(3):1008-21
references.pmid: 19007893
references.citation: Am J Clin Nutr. 2006 Dec;84(6):1365-73
references.pmid: 17158418
references.citation: Neurosci Biobehav Rev. 1986 Fall;10(3):295-315
references.pmid: 3095717
references.citation: Regul Pept. 2004 Jun 15;119(1-2):77-81
references.pmid: 15093700
references.citation: Eur J Clin Nutr. 1996 Jul;50(7):409-17
references.pmid: 8862476
references.citation: Int J Obes (Lond). 2009 Jun;33 Suppl 2:S8-13
references.pmid: 19528982
references.citation: J Clin Endocrinol Metab. 2001 Dec;86(12):5992
references.pmid: 11739476
references.citation: Science. 2003 Aug 22;301(5636):1104-7
references.pmid: 12934011
references.citation: Chem Senses. 2007 Jul;32(6):569-81
references.pmid: 17495173
references.citation: Behav Brain Res. 2006 Apr 25;169(1):111-9
references.pmid: 16445991
references.citation: Nature. 2007 Nov 1;450(7166):106-9
references.pmid: 17934448
references.citation: Appl Physiol Nutr Metab. 2007 Feb;32(1):61-75
references.pmid: 17332785
references.citation: N Engl J Med. 2008 Dec 11;359(24):2558-66
references.pmid: 19073975
references.citation: Am J Clin Nutr. 2006 Jun;83(6):1297-305
references.pmid: 16762940
references.citation: Cereb Cortex. 2003 Oct;13(10):1064-71
references.pmid: 12967923
references.citation: PLoS One. 2012;7(11):e49131
references.pmid: 23155456
references.citation: Science. 2007 May 11;316(5826):889-94
references.pmid: 17434869
references.citation: Obesity (Silver Spring). 2008 May;16(5):945-50
references.pmid: 18292747
references.citation: Chem Senses. 2009 Nov;34(9):739-51
references.pmid: 19833660
references.citation: Neuroimage. 2013 Feb 15;67:322-30
references.pmid: 23201365
references.citation: Cereb Cortex. 2008 Nov;18(11):2604-13
references.pmid: 18308706
references.citation: Am J Clin Nutr. 2006 Oct;84(4):725-31
references.pmid: 17023697
references.citation: Cell Metab. 2008 May;7(5):400-9
references.pmid: 18460331
references.citation: Neuron. 2006 Jan 5;49(1):157-66
references.pmid: 16387647
references.citation: Behav Neurosci. 2001 Apr;115(2):493-500
references.pmid: 11345973
references.citation: Physiol Behav. 2004 Aug;82(1):109-14
references.pmid: 15234598
references.citation: Chem Senses. 2012 Nov;37(9):769-97
references.pmid: 22832483
references.citation: Science. 1983 Apr 22;220(4595):431-3
references.pmid: 6836286
references.citation: Science. 1968 Aug 23;161(3843):751-6
references.pmid: 5663800
references.citation: Physiol Behav. 2011 Apr 18;103(1):59-68
references.pmid: 21167850
references.citation: Behav Neurosci. 1985 Dec;99(6):1031-9
references.pmid: 3843537
references.citation: Neuroimage. 2008 Feb 15;39(4):1559-69
references.pmid: 18096409
references.citation: Am J Clin Nutr. 2002 Jun;75(6):1017-22
references.pmid: 12036808
references.citation: Am J Clin Nutr. 2013 Mar;97(3):471-9
references.pmid: 23364016
references.citation: J Clin Invest. 2013 Aug;123(8):3539-51
references.pmid: 23867619
references.citation: J Neurophysiol. 2001 Mar;85(3):1315-21
references.pmid: 11248000
references.citation: Neuron. 2002 Feb 28;33(5):815-26
references.pmid: 11879657
references.citation: Neuroimage. 2008 Feb 15;39(4):1824-31
references.pmid: 18155924
references.citation: Science. 2008 Oct 17;322(5900):449-52
references.pmid: 18927395
references.citation: Chem Senses. 1996 Jun;21(3):323-34
references.pmid: 8670711
references.citation: J Neurosci. 2010 Oct 27;30(43):14346-55
references.pmid: 20980590
references.citation: Brain Res. 2010 Sep 2;1350:159-66
references.pmid: 20423700
references.citation: J Clin Endocrinol Metab. 2008 Sep;93(9):3640-3
references.pmid: 18583465
references.citation: Hippocampus. 2009 Mar;19(3):235-52
references.pmid: 18831000
references.citation: J Neurosci. 2001 Jul 15;21(14):5304-10
references.pmid: 11438606
references.citation: Physiol Behav. 2008 Aug 6;94(5):722-8
references.pmid: 18499202
references.citation: Am J Clin Nutr. 2009 Dec;90(6):1453-6
references.pmid: 19828708
references.citation: Obesity (Silver Spring). 2008 Aug;16(8):1961-5
references.pmid: 18551109
references.citation: Science. 2009 May 1;324(5927):646-8
references.pmid: 19407204
references.citation: Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4569-74
references.pmid: 10200303
references.citation: Obes Res. 2001 Nov;9(11):676-84
references.pmid: 11707534
references.citation: Neurosci Biobehav Rev. 2011 Apr;35(5):1219-36
references.pmid: 21185861
references.citation: Hippocampus. 1999;9(2):143-57
references.pmid: 10226775
references.citation: Hum Brain Mapp. 2003 Oct;20(2):116-21
references.pmid: 14505337
references.citation: J Endocrinol Invest. 2001 Jun;24(6):RC19-21
references.pmid: 11434675
references.citation: Behav Brain Res. 2009 Mar 2;198(1):149-58
references.pmid: 19028527
references.citation: Curr Opin Pharmacol. 2007 Dec;7(6):613-6
references.pmid: 18032108
references.citation: Diabetes. 2000 May;49(5):838-46
references.pmid: 10905495
references.citation: Brain. 2001 Sep;124(Pt 9):1720-33
references.pmid: 11522575
references.citation: Neuroreport. 2000 Mar 20;11(4):893-7
references.pmid: 10757540
references.citation: Eur J Neurosci. 2009 Oct;30(8):1625-35
references.pmid: 19811532
references.citation: Eat Behav. 2003 Aug;4(2):197-209
references.pmid: 15000982
references.citation: Neuron. 2011 Feb 24;69(4):664-79
references.pmid: 21338878
references.citation: Neuroimage. 2004 May;22(1):360-6
references.pmid: 15110027
references.citation: Int J Obes (Lond). 2009 Jan;33(1):42-5
references.pmid: 18838977
references.citation: J Clin Invest. 1956 Feb;35(2):150-4
references.pmid: 13286333