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.

The neurobiology of appetite: hunger as addiction

“…[19][20][21] Functional magnetic resonance imaging studies in humans have confirmed that the appetite-stimulating hormone, ghrelin, enhances the response of the reward system to food cues 22 whereas the anorexigenic peptides, PYY and leptin, also act on reward related brain areas. 23,24 Another similarity between feeding and addiction is the important role of stress in both behaviors. Stress is a major cause of relapse among abstinent drug users and also a significant cause of failure in dieters.…”

Promise and limitations of functional neuroimaging in the study of obesity: is it time for a consortium and a multicenter trial?

“…All these pharmacological (by the administration of so-called 'biologics') intervention studies have confirmed that the central control of eating behavior is operated by brain regions spanning the cortical and subcortical levels, although the consistency of region-specific findings across studies is rather limited. 8,[11][12][13][14] All in all, many of the FN reports await confirmation in independent studies. On the other hand, differences in subject characteristics, study designs, scanners, data acquisition and analysis procedures across studies limit the utility of retrospective cross-validation of FN findings.…”

“…Two studies 13,14 have also described the effects of leptin administration on the brain response to visual food cues in leptin-deficient individuals, who are affected by a very rare genetic form of extreme obesity, though highly responsive to leptin treatment. Another study 8 described the brain response to the administration of PYY 3À36 , an anorexigenic hormone, in normal-weight individuals, also showing that some changes in local neural activity were correlated with subsequent food intake. All these pharmacological (by the administration of so-called 'biologics') intervention studies have confirmed that the central control of eating behavior is operated by brain regions spanning the cortical and subcortical levels, although the consistency of region-specific findings across studies is rather limited.…”

Peripheral signalling involved in energy homeostasis control

“…This occurs through modulation of different cortical and hypothalamic brain areas (322) . However, these anorexigenic effects of PYY 3 -36 have not been confirmed by others (323) .…”