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

Abstract

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 intakereducing 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.

Leptin receptor expression in hindbrain Glp-1 neurons regulates food intake and energy balance in mice

“…Several studies have demonstrated that leptin reduces the amount of food consumed during the refeeding phase (reviewed in ref. 33), illustrating the physiological relevance and potency of leptin in the control of metabolic homeostasis. Following the fast, Lepr-null mice displayed more hyperphagia when refed ( Figure 3B), suggesting leptin action is required not only for the regulation of food intake in the fed state but also in the response to fasting as well.…”

Nicotinic Regulation of Energy Homeostasis

“…The NTS, a complex brain stem nucleus located in the dorsal medulla oblongata, plays a prominent role as an input station to energy metabolism control systems (Grill & Hayes, 2009). Its rostral part receives taste afferents, whereas its intermediate portion receives gastrointestinal afferents.…”

The role of relaxin-3 and its receptor RXFP3 in defense of elevated body weight in diet-induced obesity

“…The NTS is the first brain relay for the vagal sensory signals, and the NTS neurons directly project to the NI, CeA, and PVNp [140][141][142] . The direct effects of relaxin-3 in the CeA and NTS have not yet been shown, but given the important role of these brain structures in feeding behavior [143][144][145][146][147] , increased RXFP3 expression in the CeA and NTS in DIO rats during refeeding may contribute to an increase in sensitivity to the orexigenic effects of relaxin-3. In the NI, RXFP3 may be involved in autoregulating the expression of relaxin-3 or other neuropeptides expressed in this brain nucleus such as galanin, cholecystokinin, and somatostatin [56,148] .…”