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Brain-gut axis and its role in the control of food intake.
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2004
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NutritionFood IntakeSatiety ResearchDigestive TractHypothalamic CircuitsGastrointestinal Peptide HormoneObesityBrain-gut AxisHypothalamic PeptideGut-organ AxisPublic HealthAppetite ControlAppetiteBehavioral NeuroscienceFood DigestionNeuropharmacologyAfferent NervesNervous SystemEndocrinologyPharmacologyNeurophysiologyPhysiologyNeuropeptide ReceptorNeuroscienceCentral Nervous SystemLeptin ActsGut HealthMedicineNeuropeptides
The gut–brain axis involves bidirectional communication between the gastrointestinal tract and central/enteric nervous systems, with afferent nerves sensing mechanical, chemical, and nociceptive signals that influence appetite via leptin, neuropeptide Y, and gut hormones such as CCK, PYY, OXM, ghrelin, and orexins, thereby regulating short‑term and long‑term food intake. Disruption of this gut–brain regulatory balance can lead to feeding disorders, including obesity or cachexia.
Gastrointestinal tract (GIT) and nervous system, both central (CNS) and enteric (ENS), are involved in two-way extrinsic communication by parasympathetic and sympathetic nerves, each comprising efferents fibers such as cholinergic and noradrenergic, respectively, and afferent sensory fibers required for gut-brain signaling. Afferent nerves are equipped with numerous sensors at their terminals in the gut related to visceral mechano- chemo- and noci-receptors, whose excitations may trigger a variety of visceral reflexes regulating GIT functions, including the appetitive behaviour. Food intake depends upon various influences from the CNS as well as from the body energy stores (adipocytes) that express and release the product of Ob gene, leptin, in proportion to fat stored and acting in long-term regulation of food intake. Leptin acts through receptors (Ob-R) present in afferent visceral nerves and hypothalamic arcuate nucleus (ARC), whose neurons are capable of expressing and releasing neuropeptide Y (NPY) and agouti related protein (AgRP) that activate the ingestive behaviour through paraventricular nucleus (PVN) (iVfeeding centerli). In addition, to this long-term regulation, a short-term regulation, on meal-to-meal basis, is secured by several gut hormones, such as cholecystokinin (CCK), peptides YY (PYY) and oxyntomodulin (OXM), released from the endocrine intestinal cells and acting via G-protein coupled receptors (GPCR) either on afferent nerves or directly on ARC neurons, which in turn inhibit expression and release of food-intake stimulating NPY and AgRP, thereby inducing satiety through inhibition of PVN. In contrast, during fasting, the GIT, especially oxyntic mucosa, expresses and releases appetite stimulating (orexigenic) factors such as ghrelin and orexins (OX) -A and OX-B, and cannabinoid CB1 agonist. Ghrelin activates growth-hormone secretagogue receptor (GHS-R) in hypothalamic ARC and stimulates growth hormone (GH) release and in vagal afferents to promote the expression and release of hypothalamic NPY and AgRP stimulating PVN and driving ingestive behaviour. The balance and interaction between anorexigenic (CCK, PYY, OXM) and orexigenic (ghrelin and OX) factors originating from GIT appears to play an important role in short-term regulation of food intake and growth hormone (GH) release. An impairment of this balance may result in disorders of feeding behaviour and weight gain (obesity) or weight loss (cachexia).