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 weight1, 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 regions3. 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 humans1, 4, 5. 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.
SourceAvailable from: Hans Eickhoff02/2015, Degree: PhD, Supervisor: Francisco Castro e Sousa
Article: PYY3–36: Beyond food intake[Show abstract] [Hide abstract]
ABSTRACT: The gastrointestinal hormone peptide tyrosine tyrosine 3-36 (PYY3-36) has attained broad recognition with respect to its involvement in energy homeostasis and the control of food intake. It is mainly secreted by distal intestinal enteroendocrine L-cells in response to eating and exerts both neurally mediated paracrine and endocrine effects on various target organs. In addition to its gastrointestinal effects, PYY3-36 has long been known to inhibit food intake. Recent closer examination of the effects of PYY3-36 revealed that this gut-derived peptide also influences a wide spectrum of behavioral and cognitive functions that are pivotal for basic processes of perception and judgment, including central information processing, salience learning, working memory, and behavioral responding to novelty. Here, we review the effects of PYY3-36 that go beyond food intake and provide a conceptual framework suggesting that several apparently unrelated behavioral actions of PYY3-36 may actually reflect different manifestations of modulating the central dopamine system. Copyright © 2014. Published by Elsevier Inc.Frontiers in Neuroendocrinology 12/2014; DOI:10.1016/j.yfrne.2014.12.003 · 7.58 Impact Factor
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ABSTRACT: Bariatric surgery is the most effective treatment for severe obesity, producing marked sustained weight loss with associated reduced morbidity and mortality. Roux-en-Y gastric bypass surgery (RYGBP), the most commonly performed procedure, was initially viewed as a hybrid restrictive-malabsorptive procedure. However, over the last decade, it has become apparent that alternative physiologic mechanisms underlie its beneficial effects. RYGBP-induced altered feeding behavior, including reduced appetite and changes in taste/food preferences, is now recognized as a key driver of the sustained postoperative weight loss. The brain ultimately determines feeding behavior, and here we review the mechanisms by which RYGBP may affect central appetite-regulating pathways.Journal of Clinical Investigation 03/2015; 125(3):939-948. DOI:10.1172/JCI76305 · 13.77 Impact Factor