Grill HJ, Hayes MR. The nucleus tractus solitarius: a portal for visceral afferent signal processing, energy status assessment and integration of their combined effects on food intake. Int J Obes (Lond) 33(Suppl 1): S11-S15

Psychology and Neuroscience, University of Pennsylvania, Philadelphia, PA, USA.
International journal of obesity (2005) (Impact Factor: 5). 05/2009; 33 Suppl 1(Suppl 1):S11-5. DOI: 10.1038/ijo.2009.10
Source: PubMed


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.

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Available from: Harvey Grill, Jun 16, 2015
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    • "The central sites integrating hunger and satiety signals such as the hypothalamus and brainstem are potential drug target areas to treat eating disorders and obesity (Grill and Hayes, 2009; Berthoud, 2012). Among the involved signals is a-melanocyte-stimulating hormone (a-MSH), a 13 amino acid acylated neuropeptide produced in the arcuate nucleus of the hypothalamus (Harris and Lerner, 1957). "
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    • "The NTS is formed by heterogeneous groups of neurons located in the dorsolateral medulla, extending from the level of caudal portion of the facial nucleus to the caudal portion of the pyramidal decussation (Loewy, 1990; Dampney, 1994). Previous studies have demonstrated that the NTS plays a key role in the processing of visceral afferent information and transmission to other nuclei in the brainstem, forebrain and spinal cord (for review, see Andresen and Kunze, 1994; Sapru, 1996; Johnson and Thunhorst, 1997; Grill and Hayes, 2009). With respect to the cardiovascular and respiratory systems, the majority of the cardiorespiratory afferents converges preferentially to two different regions of the NTS: the intermediate NTS (iNTS), at the level of the area postrema, and the caudal NTS (cNTS), located caudal to the calamus scriptorius (Kumada et al., 1990; Loewy, 1990; Van Giersbergen et al., 1992). "
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