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Gaining insights into how the gut-brain axis regulates feeding behaviour
Complex interrelated neuronal circuits have developed in the mammalian brain to regulate many aspects of feeding behaviour. An increased understanding of how peripheral energy signals act upon these circuits to regulate food intake is essential for effective treatment of the current obesity crisis. We have shown that the gut hormone peptide YY (PYY) regulates feeding behaviour in rodents and humans and identified that the neuropeptide Y2 receptor is crucial for the anorectic effects of PYY. By generating mice-lacking PYY we have shown that this hormone plays a crucial role in the regulation of body weight. Moreover, we have shown that infusion of PYY reduces food intake in obese human subjects. Using fMRI in healthy male volunteers we have shown that PYY modulates neuronal activity within both homeostatic (hypothalamic and brainstem) and hedonic (orbitofrontal cortex) brain regions. More recently, again using fMRI we have shown that the neural response to visual food images within key brain appetite and reward brain regions in markedly altered in normal weight subjects carrying two copies of the obesity-risk FTO gene variant.
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