PYY modulation of cortical and hypothalamic brain areas predicts feeding behaviour in humans

• Published in: Nature Vol. 450; no. 7166; pp. 106 - 109
• Main Authors: Batterham, Rachel L., ffytche, Dominic H., Rosenthal, J. Miranda, Zelaya, Fernando O., Barker, Gareth J., Withers, Dominic J., Williams, Steven C. R.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.11.2007; Nature Publishing; Nature Publishing Group
• Subjects: Appetite Regulation - drug effects; Appetite Regulation - physiology; Behavior; Biological and medical sciences; Body weight; Brain; Cerebral Cortex - anatomy & histology; Cerebral Cortex - drug effects; Cerebral Cortex - physiology; Cross-Over Studies; Feeding behavior; Feeding Behavior - drug effects; Feeding Behavior - physiology; Feeding. Feeding behavior; Food; Fundamental and applied biological sciences. Psychology; Homeostasis - drug effects; Humanities and Social Sciences; Humans; Hypothalamus - drug effects; Hypothalamus - physiology; letter; Male; Mammals; multidisciplinary; Neurons; Neurosciences; Nutrients; Obesity; Peptide YY - blood; Peptide YY - metabolism; Peptide YY - pharmacology; Peptides; Physiology; Satiation - drug effects; Satiation - physiology; Science; Science (multidisciplinary); Vertebrates: anatomy and physiology, studies on body, several organs or systems; Human; Orbitofrontal cortex; Feeding behavior; Central nervous system; Satiety; Limbic system; Hypothalamus; Nuclear magnetic resonance imaging; YY peptide; Encephalon; Feeding; Functional imaging
• ISSN: 0028-0836; 1476-4687; 1476-4687; 1476-4679
• DOI: 10.1038/nature06212

Functional magnetic resonance imaging is used to examine brain areas whose activity correlates with subsequent feeding behaviour under different satiety states evoked by intravenous peptide YY 3–36 (PYY), administration. Under high PYY conditions, (mimicking the fed state) changes in orbitofrontal cortex activation better predicted subsequent feeding, whereas in low PYY conditions, hypothalamic activation predicted food intake. 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 1 , 2 . 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 3 . 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 1 , 4 , 5 . Here we show, using functional magnetic resonance imaging, that peptide YY 3–36 (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.