title: Basolateral amygdala response to food cues in the absence of hunger is associated with weight gain susceptibility.
abstract: In rodents, food-predictive cues elicit eating in the absence of hunger (Weingarten, 1983). This behavior is disrupted by the disconnection of amygdala pathways to the lateral hypothalamus (Petrovich et al., 2002). Whether this circuit contributes to long-term weight gain is unknown. Using fMRI in 32 healthy individuals, we demonstrate here that the amygdala response to the taste of a milkshake when sated but not hungry positively predicts weight change. This effect is independent of sex, initial BMI, and total circulating ghrelin levels, but it is only present in individuals who do not carry a copy of the A1 allele of the Taq1A polymorphism. In contrast, A1 allele carriers, who have decreased D2 receptor density (Blum et al., 1996), show a positive association between caudate response and weight change. Regardless of genotype, however, dynamic causal modeling supports unidirectional gustatory input from basolateral amygdala (BLA) to hypothalamus in sated subjects. This finding suggests that, as in rodents, external cues gain access to the homeostatic control circuits of the human hypothalamus via the amygdala. In contrast, during hunger, gustatory inputs enter the hypothalamus and drive bidirectional connectivity with the amygdala. These findings implicate the BLA-hypothalamic circuit in long-term weight change related to nonhomeostatic eating and provide compelling evidence that distinct brain mechanisms confer susceptibility to weight gain depending upon individual differences in dopamine signaling.
authors.affiliation: Interdepartmental Neuroscience Program, Yale School of Medicine, New Haven, Connecticut 06520, The John B. Pierce Laboratory, New Haven, Connecticut 06519, xue.sun@yale.edu dana.small@yale.edu.
authors.forename: Xue
authors.identifier: http://orcid.org/0000-0001-9234-561X
authors.initials: X
authors.lastname: Sun
authors.affiliation: The John B. Pierce Laboratory, New Haven, Connecticut 06519, Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut 06511, Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden 01187, Germany.
authors.forename: Nils B
authors.initials: NB
authors.lastname: Kroemer
authors.affiliation: The John B. Pierce Laboratory, New Haven, Connecticut 06519, Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut 06511.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Veldhuizen
authors.affiliation: The John B. Pierce Laboratory, New Haven, Connecticut 06519.
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Babbs
authors.affiliation: The John B. Pierce Laboratory, New Haven, Connecticut 06519, Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut 06511.
authors.forename: Ivan E
authors.initials: IE
authors.lastname: de Araujo
authors.affiliation: The John B. Pierce Laboratory, New Haven, Connecticut 06519, Advocate Lutheran General Hospital, Park Ridge, Illinois 60068, Department of Neurology, Rosalind Franklin University Medical School, North Chicago, Illinois 60064, Department of Neurology and Radiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611.
authors.forename: Darren R
authors.initials: DR
authors.lastname: Gitelman
authors.affiliation: Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut 06520, and.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Sherwin
authors.affiliation: Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut 06511.
authors.forename: Rajita
authors.initials: R
authors.lastname: Sinha
authors.affiliation: Interdepartmental Neuroscience Program, Yale School of Medicine, New Haven, Connecticut 06520, Department of Psychology, Yale University, New Haven, Connecticut 06520, The John B. Pierce Laboratory, New Haven, Connecticut 06519, Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut 06511, Center for Excellence, University of Cologne, Cologne 50931, Germany xue.sun@yale.edu dana.small@yale.edu.
authors.forename: Dana M
authors.initials: DM
authors.lastname: Small
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D000679:Amygdala / Q000502:physiology*; D003463:Cues; D005260:Female; D006801:Humans; D006815:Hunger; D007031:Hypothalamus / Q000502:physiology; D008297:Male; D011110:Polymorphism, Genetic; D017448:Receptors, Dopamine D2 / Q000235:genetics; D012527:Satiation; D015430:Weight Gain / Q000235:genetics / Q000502:physiology*
chemical_list: C581293:DRD2 protein, human; D017448:Receptors, Dopamine D2
keywords: TaqIA; fMRI; feeding; metabolism; obesity; satiety