nucleus tractus solitarius: a portal for visceral afferent signal processing, energy status assessment and integration of their combined effects on food intake

• Published in: International Journal of Obesity 2009-04, Vol.33 (S1), p.S11-S15
• Main Authors: Grill, H.J, Hayes, M.R
• Format: Article
• Language: English
• Subjects: Animal models; Animal models in research; Animals; Appetite Regulation - drug effects; Appetite Regulation - physiology; brain stem; Brain Stem - drug effects; Brain Stem - physiology; Central nervous system; Control; Diabetes; Eating - physiology; Energy; Energy balance; Energy Metabolism - physiology; Epidemiology; Food; Food consumption; food intake; Gastric Emptying; gastrointestinal hormones; Genetic aspects; Glucagon; Glucagon-Like Peptide 1 - physiology; Glucagon-Like Peptide-1 Receptor; Health aspects; Health Promotion and Disease Prevention; Heart surgery; Humans; Hypothalamus; Hypothalamus - drug effects; Hypothalamus - physiology; Internal Medicine; Kinases; Leptin; Leptin - pharmacology; Leptin - physiology; Ligands; literature reviews; Medicine; Medicine & Public Health; Metabolic Diseases; Nervous system; Neurons, Afferent - drug effects; Neurons, Afferent - physiology; neurophysiology; Neurosciences; nucleus tractus solitarius; Nutrients; nutrition assessment; nutrition physiology; nutritional status; Obesity; Peptides; Physiological aspects; Public Health; Rats; Receptors, Glucagon - agonists; Receptors, Glucagon - metabolism; review; Risk factors; Satiation - drug effects; sensory neurons; Signal processing; signal transduction; Solitary Nucleus - drug effects; Solitary Nucleus - physiology; Success; vagal afferent neurons; Visceral Afferents - physiology; Weight control
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/ijo.2009.10

For humans and animal models alike there is general agreement that the central nervous system processing of gastrointestinal (GI) signals arising from ingested food provides the principal determinant of the size of meals and their frequency. Despite this, relatively few studies are aimed at delineating the brain circuits, neurochemical pathways and intracellular signals that mediate GI-stimulation-induced intake inhibition. Two additional motivations to pursue these circuits and signals have recently arisen. First, the success of gastric-bypass surgery in obesity treatment is highlighting roles for GI signals such as glucagon-like peptide-1 (GLP-1) in intake and energy balance control. Second, accumulating data suggest that the intake-reducing effects of leptin may be mediated through an amplification of the intake-inhibitory effects of GI signals. Experiments reviewed show that: (1) the intake-suppressive effects of a peripherally administered GLP-1 receptor agonist is mediated by caudal brainstem neurons and that forebrain-hypothalamic neural processing is not necessary for this effect; (2) a population of medial nucleus tractus solitarius (NTS) neurons that are responsive to gastric distention is also driven by leptin; (3) caudal brainstem-targeted leptin amplifies the food-intake-inhibitory effects of gastric distention and intestinal nutrient stimulation; (4) adenosine monophosphate-activated protein kinase (AMPK) activity in NTS-enriched brain lysates is elevated by food deprivation and reduced by refeeding and (5) the intake-suppressive effect of hindbrain-directed leptin is reversed by elevating hindbrain AMPK activity. Overall, data support the view that the NTS and circuits within the hindbrain mediate the intake inhibition of GI signals, and that the effects of leptin on food intake result from the amplification of GI signal processing.