title: PYY modulation of cortical and hypothalamic brain areas predicts feeding behaviour in humans.
abstract: The ability to maintain adequate nutrient intake is critical for survival. Complex interrelated neuronal circuits have developed in the mammalian brain to regulate many aspects of feeding behaviour, from food-seeking to meal termination. The hypothalamus and brainstem are thought to be the principal homeostatic brain areas responsible for regulating body weight. However, in the current 'obesogenic' human environment food intake is largely determined by non-homeostatic factors including cognition, emotion and reward, which are primarily processed in corticolimbic and higher cortical brain regions. Although the pleasure of eating is modulated by satiety and food deprivation increases the reward value of food, there is currently no adequate neurobiological account of this interaction between homeostatic and higher centres in the regulation of food intake in humans. Here we show, using functional magnetic resonance imaging, that peptide YY3-36 (PYY), a physiological gut-derived satiety signal, modulates neural activity within both corticolimbic and higher-cortical areas as well as homeostatic brain regions. Under conditions of high plasma PYY concentrations, mimicking the fed state, changes in neural activity within the caudolateral orbital frontal cortex predict feeding behaviour independently of meal-related sensory experiences. In contrast, in conditions of low levels of PYY, hypothalamic activation predicts food intake. Thus, the presence of a postprandial satiety factor switches food intake regulation from a homeostatic to a hedonic, corticolimbic area. Our studies give insights into the neural networks in humans that respond to a specific satiety signal to regulate food intake. An increased understanding of how such homeostatic and higher brain functions are integrated may pave the way for the development of new treatment strategies for obesity.
authors.affiliation: Centre for Diabetes and Endocrinology, Department of Medicine, University College London, London WC1E 6JJ, UK. r.batterham@ucl.ac.uk
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Batterham
authors.forename: Dominic H
authors.initials: DH
authors.lastname: ffytche
authors.forename: J Miranda
authors.initials: JM
authors.lastname: Rosenthal
authors.forename: Fernando O
authors.initials: FO
authors.lastname: Zelaya
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Barker
authors.forename: Dominic J
authors.initials: DJ
authors.lastname: Withers
authors.forename: Steven C R
authors.initials: SC
authors.lastname: Williams
mesh_terms: D001069:Appetite Regulation / Q000187:drug effects* / Q000502:physiology; D002540:Cerebral Cortex / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology*; D018592:Cross-Over Studies; D005247:Feeding Behavior / Q000187:drug effects* / Q000502:physiology; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D019894:Peptide YY / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D012527:Satiation / Q000187:drug effects / Q000502:physiology
chemical_list: D019894:Peptide YY