High Fat Diet Suppresses Energy Expenditure Via Neurons in the Brainstem.

Oxidation of fat by brown adipose tissue (BAT) contributes to energy balance and heat production. During cold exposure, BAT thermogenesis produces heat to warm the body. Obese subjects and rodents, however, show impaired BAT thermogenesis to the cold. Our previous studies suggest that vagal afferents synapsing in the nucleus tractus solitarius (NTS), tonically inhibit BAT thermogenesis to the cold in obese rats. NTS neurons send projections to the dorsal aspect of the lateral parabrachial nucleus (LPBd), which is a major integrative center that receives warm afferent inputs from the periphery and promotes inhibition of BAT thermogenesis. This study investigated the contribution of LPBd neurons in the impairment of BAT thermogenesis in rats fed a high-fat diet (HFD). By using a targeted dual viral vector approach, we found that chemogenetic activation of an NTS-LPB pathway inhibited BAT thermogenesis to the cold. We also found that the number of Fos-labelled neurons in the LPBd was higher in rats fed a HFD than in chow diet-fed rats after exposure to a cold ambient temperature. Nanoinjections of a GABAA receptor agonist into the LPBd area rescued BAT thermogenesis to the cold in HFD rats. These data reveal the LPBd as a critical brain area that tonically suppresses energy expenditure in obesity during skin cooling. These findings reveal novel effects of high-fat diets in the brain and in the control of metabolism and can contribute to the development of therapeutic approaches to regulate fat metabolism.

Monosynaptic convergence of chorda tympani and glossopharyngeal afferents onto ascending relay neurons in the nucleus of the solitary tract: a high-resolution confocal and correlative electron microscopy approach.

Physiological studies suggest convergence of chorda tympani and glossopharyngeal afferent axons onto single neurons of the rostral nucleus of the solitary tract (rNTS), but anatomical evidence has been elusive. The current study uses high-magnification confocal microscopy to identify putative synaptic contacts from afferent fibers of the two nerves onto individual projection neurons. Imaged tissue is revisualized with electron microscopy, confirming that overlapping fluorescent signals in confocal z-stacks accurately identify appositions between labeled terminal and dendrite pairs. Monte Carlo modeling reveals that the probability of overlapping fluorophores is stochastically unrelated to the density of afferent label, suggesting that convergent innervation in the rNTS is selective rather than opportunistic. Putative synaptic contacts from each nerve are often compartmentalized onto dendrite segments of convergently innervated neurons. These results have important implications for orosensory processing in the rNTS, and the techniques presented here have applications in investigations of neural microcircuitry with an emphasis on innervation patterning.

Ascending projections from the caudal visceral nucleus of the solitary tract to brain regions involved in food intake and energy expenditure.

Metabolic homeostasis reflects the complex output of endocrine, autonomic, and behavioral control circuits that extend throughout the central nervous system. Brain regions that control food intake and energy expenditure are privy to continuous visceral sensory feedback signals that presumably modulate appetite, satiety, digestion, and metabolism. Sensory signals from the gastrointestinal tract and associated digestive viscera are delivered to the brain primarily by vagal afferents that terminate centrally within the caudal nucleus of the solitary tract (NST), with signals subsequently relayed to higher brain regions by parallel noradrenergic and peptidergic projection pathways arising within the NST. This article begins with an overview of these ascending pathways identified in adult rats using a standard anterograde tracer microinjected into the caudal visceral sensory region of the NST, and also by immunocytochemical localization of glucagon-like peptide-1. NST projection targets identified by these two approaches are compared to the distribution of neurons that become infected after inoculating the ventral stomach wall with a neurotropic virus that transneuronally infects synaptically-linked chains of neurons in the anterograde (i.e., ascending sensory) direction. Although the focus of this article is the anatomical organization of axonal projections from the caudal visceral NST to the hypothalamus and limbic forebrain, discussion is included regarding the hypothesized role of these projections in modulating behavioral arousal and coordinating endocrine and behavioral (i.e., hypophagic) responses to stress.

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

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.

Os núcleos vasomotores do bulbo e a regulação cardiovascular: novas evidências e novas questões / Ventrolateral medulla and the cardiovascular control: new evidence new doubts

RESUMO: Há mais de 30 anos foi proposto um modelo para explicar como o sistema nervoso central promove a regulação do sistema cardiovascular, onde os núcleos vasomotores do bulbo seriam as principais estruturas envolvidas no controle do reflexo cardiovascular. Segundo este modelo, o núcleo do trato solitário (NTS) é o primeiro núcleo a integrar as informações cardiovasculares vindas dos baroceptores e também parece integrar vias descendentes provenientes de núcleos superiores como o hipotálamo, importantes para as reações de alerta e defesa. Do NTS saem projeções excitatórias para a região caudoventrolateral (CVL) do bulbo, a qual inibe a região rostroventrolateral (RVL). Esta última região constitui a principal fonte de eferências excitatórias para os neurônios simpáticos pré-ganglionares (SPN), sendo responsável pelo tonus simpático para o coração e vasos. Projeções importantes do CVL para estruturas diencefálicas (núcleo preóptico mediano, núcleo paraventricular do hipotálamo e núcleo supraóptico) também estão envolvidas no controle da composição e/ou volume do compartimento extracelular. A área depressora gigantocelular (GiDA) constitui outro possível centro vasomotor envolvido nos ajustes de fluxo sangüíneo por meio de projeções diretas para o SPN. No entanto, o meio pelo qual a GiDA exerce seu efeito vasodepressor ainda é desconhecido.Nos últimos 10 anos, nosso laboratório tem se dedicado a deslindar as vias e mecanismos neurais associados à regulação do fluxo sangüineo visceral e muscular. Resultados obtidos ao longo destes estudos resultaram em evidências que são incompatíveis com o modelo proposto.