RESUMEN
Monosodium L-glutamate (MSG) and inosine monophosphate-5 (IMP) are flavor enhancers for umami taste. However, their effects on appetite and food intake are not well-researched. The objective of the current study was to test their additions in a broth preload on subsequent appetite ratings, energy intake and food choice. Eighty-six healthy middle-aged women with normal body weight received three preload conditions on 3 test days 1 week apart - a low-energy chicken flavor broth (200 ml) as the control preload, and broths with added MSG alone (0.5 g/100 ml, MSG broth) or in combination with IMP (0.05 g/100 ml) (MSG+ broth) served as the experimental conditions. Fifteen minutes after preload administration subjects were provided an ad libitum testing meal which consisted of 16 snacks varying in taste and fat content. MSG and MSG+ enhanced savory taste and broth properties of liking and pleasantness. In comparison with control, the MSG preload resulted in less consumption of total energy, as well as energy from sweet and high-fat snacks. Furthermore, MSG broth preload reduced added sugar intake. These findings were not observed after MSG+ preload. Appetite ratings were not different across the three preloads. Results suggest a potential role of MSG addition to a low-energy broth preload in subsequent energy intake and food choice. This trial was registered at clinicaltrials.gov as NCT01761045.
Asunto(s)
Grasas de la Dieta/administración & dosificación , Sacarosa en la Dieta/administración & dosificación , Ingestión de Energía/efectos de los fármacos , Carne , Bocadillos/efectos de los fármacos , Glutamato de Sodio/farmacología , Gusto , Adulto , Animales , Pollos , Dieta , Suplementos Dietéticos , Femenino , Aromatizantes/farmacología , Humanos , PlacerRESUMEN
The concentration of free glutamate (Glu) in rat's milk is â¼10 times higher than that in plasma. Previous work has shown that mammary tissue actively transports circulatory leucine (Leu), which is transaminated to synthesize other amino acids such as Glu and aspartate (Asp). To investigate the molecular basis of Leu transport and its conversion into Glu in the mammary gland, we characterized the expression of Leu transporters and [(3)H]Leu uptake in rat mammary cells. Gene expression analysis indicated that mammary cells express two Leu transporters, LAT1 and LAT2, with LAT1 being more abundant than LAT2. This transport system is sodium independent and transports large neutral amino acids. The Leu transport system in isolated rat mammary cells could be specifically blocked by the LAT1 inhibitors 2-aminobicyclo-[2.2.1]-heptane-2-carboxylic acid (BCH) and triiodothyronine (T3). In organ cultures, Glu secretion was markedly inhibited by these LAT1 inhibitors. Furthermore, the profiles of Leu uptake inhibition by amino acids in mammary cells were similar to those reported for LAT1. In vivo, concentrations of free Glu and Asp increased in milk by oral gavage with Leu at 6, 12, and 18 days of lactation. These results indicate that the main Leu transporter in mammary tissue is LAT1 and the transport of Leu is a limiting factor for the synthesis and release of Glu and Asp into milk. Our studies provide the bases for the molecular mechanism of Leu transport in mammary tissue by LAT1 and its active role on free Glu secretion in milk, which confer umami taste in suckling pups.
Asunto(s)
Ácido Glutámico/biosíntesis , Transportador de Aminoácidos Neutros Grandes 1/metabolismo , Leche/metabolismo , Sistema de Transporte de Aminoácidos y+/genética , Sistema de Transporte de Aminoácidos y+/metabolismo , Aminoácidos/genética , Aminoácidos/metabolismo , Animales , Transporte Biológico , Línea Celular , Femenino , Cadenas Ligeras de la Proteína-1 Reguladora de Fusión/genética , Cadenas Ligeras de la Proteína-1 Reguladora de Fusión/metabolismo , Ácido Glutámico/genética , Ácido Glutámico/metabolismo , Transportador de Aminoácidos Neutros Grandes 1/genética , Leucina/genética , Leucina/metabolismo , Glándulas Mamarias Animales/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
Although previous studies have shown that virtually the entire carbon skeleton of dietary glutamate (glutamate-C) is metabolized in the gut for energy production and amino acid synthesis, little is known regarding the fate of dietary glutamate nitrogen (glutamate-N). In this study, we hypothesized that dietary glutamate-N is an effective nitrogen source for amino acid synthesis and investigated the fate of dietary glutamate-N using [(15)N]glutamate. Fischer male rats were given hourly meals containing [U-(13)C]- or [(15)N]glutamate. The concentration and isotopic enrichment of several amino acids were measured after 0-9 h of feeding, and the net release of each amino acid into the portal vein was calculated. Most of the dietary glutamate-C was metabolized into CO(2), lactate, or alanine (56, 13, and 12% of the dietary input, respectively) in the portal drained viscera (PDV). Most of the glutamate-N was utilized for the synthesis of other amino acids such as alanine and citrulline (75 and 3% of dietary input, respectively) in the PDV, and only minor amounts were released into the portal vein in the form of ammonia and glutamate (2 and 3% of the dietary input, respectively). Substantial incorporation of (15)N into systemic amino acids such as alanine, glutamine, and proline, amino acids of the urea cycle, and branched-chain amino acids was also evident. These results provide quantitative evidence that dietary glutamate-N distributes extensively to amino acids synthesized in the PDV and, consequently, to circulating amino acids.
Asunto(s)
Aminoácidos/biosíntesis , Dieta , Ácido Glutámico/química , Ácido Glutámico/farmacocinética , Mucosa Intestinal/metabolismo , Nitrógeno/farmacocinética , Aminoácidos/análisis , Animales , Arterias/química , Arterias/metabolismo , Carbono/química , Carbono/farmacocinética , Ingestión de Alimentos/fisiología , Intestinos/química , Masculino , Concentración Osmolar , Vena Porta/química , Vena Porta/metabolismo , Ratas , Ratas Endogámicas F344 , Factores de TiempoRESUMEN
L-Lysine (Lys) is an essential amino acid and plays an important role in anxiogenic behaviour in both human subjects and rodents. Previous studies have shown the existence of neural plasticity between the Lys-deficient state and the normal state. Lys deficiency causes an increase in noradrenaline release from the hypothalamus and serotonin release from the amygdala in rats. However, no studies have used functional MRI (fMRI) to compare the brain response to ingested Lys in normal, Lys-deficient and Lys-recovered states. Therefore, in the present study, using acclimation training, we performed fMRI on conscious rats to investigate the brain response to an intragastric load of Lys. The brain responses to intragastric administration of Lys (3 mmol/kg body weight) were investigated in six rats intermittently in three states: normal, Lys-deficient and recovered state. First, in the normal state, an intragastric load of Lys activated several brain regions, including the raphe pallidus nucleus, prelimbic cortex and the ventral/lateral orbital cortex. Then, after 6 d of Lys deprivation from the normal state, an intragastric load of Lys activated the ventral tegmental area, raphe pallidus nucleus and hippocampus, as well as several hypothalamic areas. After recovering from the Lys-deficient state, brain activation was similar to that in the normal state. These results indicate that neural plasticity in the prefrontal cortex, hypothalamic area and limbic system is related to the internal Lys state and that this plasticity could have important roles in the control of Lys intake.
Asunto(s)
Encéfalo/fisiología , Neuronas Dopaminérgicas/fisiología , Conducta Alimentaria , Lisina/metabolismo , Plasticidad Neuronal , Estado Nutricional , Animales , Conducta Animal , Encéfalo/fisiopatología , Mapeo Encefálico , Catéteres de Permanencia , Hipocampo/fisiología , Hipocampo/fisiopatología , Hipotálamo/fisiología , Hipotálamo/fisiopatología , Sistema Límbico/fisiología , Sistema Límbico/fisiopatología , Lisina/administración & dosificación , Lisina/deficiencia , Lisina/uso terapéutico , Imagen por Resonancia Magnética , Masculino , Núcleos del Rafe/fisiología , Núcleos del Rafe/fisiopatología , Ratas , Ratas Wistar , Estómago , Área Tegmental Ventral/fisiología , Área Tegmental Ventral/fisiopatologíaRESUMEN
The antibody titers of volunteers, including elderly people, were investigated after the second dose of the BNT162b2 vaccine (Pfizer-BioNTech) as an mRNA vaccine against the coronavirus disease 2019 (COVID-19). Serum samples were collected from 105 volunteers (44 healthcare workers and 61 elderly people) 7-14 days after the second vaccine dose, and antibody titers were measured. The antibody titers of study participants in their 20s were significantly higher than those of other age groups. Furthermore, the antibody titers of participants aged <60 years were significantly higher than those of participants aged ≥60 years. Serum samples were repeatedly collected from 44 healthcare workers until after the third vaccine dose. Eight months after the second round of vaccination, the antibody titer levels decreased to the same level as that before the second vaccine dose. After the third booster vaccination, the antibody titer recovered to the same level as that after the second dose. Neutralizing activities were also investigated at four time points before and after the second vaccine dose. The antibody titers and neutralizing activity were positively correlated. Therefore, neutralizing activity can be predicted by measuring the antibody titer. In conclusion, the antibody titers in the elderly population were significantly lower than those in the younger population. Although the antibody titers increased following vaccination, their levels showed a decline after several months, returning to the same level as that after a single dose of mRNA vaccination. The antibody titer levels recovered after the third dose of vaccination, which had already been administered in Japan. Routine administration of vaccine should be considered in the future.
RESUMEN
The distinctive umami taste elicited by l-glutamate and some other amino acids is thought to be initiated by G-protein-coupled receptors. Proposed umami receptors include heteromers of taste receptor type 1, members 1 and 3 (T1R1+T1R3), and metabotropic glutamate receptors 1 and 4 (mGluR1 and mGluR4). Multiple lines of evidence support the involvement of T1R1+T1R3 in umami responses of mice. Although several studies suggest the involvement of receptors other than T1R1+T1R3 in umami, the identity of those receptors remains unclear. Here, we examined taste responsiveness of umami-sensitive chorda tympani nerve fibres from wild-type mice and mice genetically lacking T1R3 or its downstream transduction molecule, the ion channel TRPM5. Our results indicate that single umami-sensitive fibres in wild-type mice fall into two major groups: sucrose-best (S-type) and monopotassium glutamate (MPG)-best (M-type). Each fibre type has two subtypes; one shows synergism between MPG and inosine monophosphate (S1, M1) and the other shows no synergism (S2, M2). In both T1R3 and TRPM5 null mice, S1-type fibres were absent, whereas S2-, M1- and M2-types remained. Lingual application of mGluR antagonists selectively suppressed MPG responses of M1- and M2-type fibres. These data suggest the existence of multiple receptors and transduction pathways for umami responses in mice. Information initiated from T1R3-containing receptors may be mediated by a transduction pathway including TRPM5 and conveyed by sweet-best fibres, whereas umami information from mGluRs may be mediated by TRPM5-independent pathway(s) and conveyed by glutamate-best fibres.
Asunto(s)
Aminoácidos/fisiología , Nervio de la Cuerda del Tímpano/fisiología , Receptores Acoplados a Proteínas G/fisiología , Receptores de Glutamato Metabotrópico/fisiología , Canales Catiónicos TRPM/fisiología , Animales , Antagonistas de Aminoácidos Excitadores/farmacología , Femenino , Glicina/análogos & derivados , Glicina/farmacología , Técnicas In Vitro , Indanos/farmacología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Fibras Nerviosas/fisiología , Receptores de Glutamato Metabotrópico/antagonistas & inhibidores , Transducción de Señal , Gusto , Lengua/fisiologíaRESUMEN
Recent studies indicate that l-glutamate (l-Glu), abundant in many foods, is a stimulator of gastric vagal afferent nerves. The aim of the present study was to examine the possibility that l-Glu supplementation of a protein-rich liquid diet may prevent the incidence of diarrhoea during repetitive intra-gastric tube feeding. The gastric vagal afferent nerve recording of rats indicated that intra-gastric administration of a protein-rich liquid diet supplemented with 0·5 % monosodium glutamate enhanced the basal afferent activities seen with the protein-rich diet alone. The examination of the faeces showed that the addition of monosodium glutamate to the liquid diet significantly prevented the incidence of diarrhoea induced by repetitive gastric feeding. In conclusion, supplementation of an enteral liquid diet with free l-Glu may ameliorate diarrhoea during intra-gastric tube feeding by sending visceral glutamate information from the stomach to the brain.
Asunto(s)
Diarrea/prevención & control , Modelos Animales de Enfermedad , Nutrición Enteral/efectos adversos , Glutamato de Sodio/uso terapéutico , Vías Aferentes , Animales , Diarrea/etiología , Proteínas en la Dieta/administración & dosificación , Heces/química , Alimentos Formulados/análisis , Masculino , Ratas , Ratas Sprague-Dawley , Índice de Severidad de la Enfermedad , Glutamato de Sodio/administración & dosificación , Estómago , Factores de Tiempo , Nervio Vago/fisiopatologíaRESUMEN
The gustatory and visceral stimulation from food regulates digestion and nutrient utilization, and free glutamate (Glu) release from food is responsible for the umami taste perception that increases food palatability. The results of recent studies reveal a variety of physiological roles for Glu. For example, luminal applications of Glu into the mouth, stomach, and intestine increase the afferent nerve activities of the glossopharyngeal nerve, the gastric branch of the vagus nerve, and the celiac branch of the vagus nerve, respectively. Additionally, luminal Glu evokes efferent nerve activation of each branch of the abdominal vagus nerve. The intragastric administration of Glu activates several brain areas (e.g., insular cortex, limbic system, and hypothalamus) and has been shown to induce flavor-preference learning in rats. Functional magnetic resonance imaging of rats has shown that the intragastric administration of Glu activates the nucleus tractus solitarius, amygdala, and lateral hypothalamus. In addition, Glu may increase flavor preference as a result of its postingestive effect. Considering these results, we propose that dietary Glu functions as a signal for the regulation of the gastrointestinal tract via the gut-brain axis and contributes to the maintenance of a healthy life.
Asunto(s)
Encéfalo/efectos de los fármacos , Tracto Gastrointestinal/efectos de los fármacos , Ácido Glutámico/farmacología , Animales , Encéfalo/metabolismo , Tracto Gastrointestinal/inervación , Tracto Gastrointestinal/metabolismo , Ácido Glutámico/administración & dosificación , Humanos , Imagen por Resonancia Magnética , Ratas , Transducción de Señal , Gusto/efectos de los fármacosRESUMEN
Neuroanatomical studies suggest that hippocampal formation (HF) receives information from all sensory modalities including taste via the parahippocampal cortices. To date, however, no neurophysiological study has reported that HF neurons encode taste information. In the present study, we recorded CA1 HF neurons from freely behaving rats during performance of a visually-guided licking task in two different triangular chambers. When a cue lamp came on, the rats were required to press a bar to trigger a tube to protrude into the chambers for 3 s. During this period, the rats could lick one of six sapid solutions: [0.1M NaCl (salty), 0.3M sucrose (sweet), 0.01 M citric acid (sour), 0.0001 M quinine HCl (bitter), 0.01 M monosodium L-glutamate (MSG, umami), and a mixture of MSG and 0.001 M disodium-5'-inosinate (IMP) (MSG+IMP)], and distilled water. Of a total 285 pyramidal and interneurons, the activity of 173 was correlated with at least one of the events in the task-illumination of cue lamps, bar pressing, or licking the solution. Of these, 137 neurons responded during licking, and responses of 62 of these cells were greater to sapid solutions than to water (taste neurons). Multivariate analyses of the taste neurons suggested that, in the HF, taste quality might be encoded based on hedonic value. Furthermore, the activity of most taste neurons was chamber-specific. These results implicate the HF in guiding appetitive behaviors such as conditioned place preference.
Asunto(s)
Potenciales de Acción/fisiología , Región CA1 Hipocampal/fisiología , Preferencias Alimentarias/fisiología , Neuronas/fisiología , Transducción de Señal/fisiología , Gusto/fisiología , Animales , Región CA1 Hipocampal/citología , Señales (Psicología) , Masculino , Estimulación Luminosa/métodos , Ratas , Ratas WistarRESUMEN
In this study, we compared the blood oxygen level-dependent (BOLD) signal changes between intragastric load of monosodium L-glutamate (MSG) and inosine monophosphate (IMP), which elicit the umami taste. An intragastric load of 30 mM IMP or 60 mM MSG induced a BOLD signal increase in several brain regions, including the nucleus of the solitary tract (NTS), lateral hypothalamus (LH), and insular cortex. Only MSG increased the BOLD signal in the amygdala (AMG). The time course of the BOLD signal changes in the NTS and the LH in the IMP group was different from that of the MSG group. We further compared the brain regions correlated with the BOLD signal change in the NTS between MSG and IMP groups. The BOLD responses in the hippocampus and the orbital cortex were associated with activation of the NTS in both MSG and IMP groups, but the association in the AMG and the pyriform was only in MSG group. These results indicate that gut stimulation with MSG and IMP evoked BOLD responses in distinct regions with different temporal patterns and that the mechanism of perception of L-glutamate and IMP in the gastrointestinal tract differed from that in the taste-sensing system.
Asunto(s)
Encéfalo/efectos de los fármacos , Ácido Glutámico/farmacología , Inosina Monofosfato/farmacología , Oxígeno/sangre , Estómago/fisiología , Animales , Encéfalo/diagnóstico por imagen , Estado de Conciencia , Imagen por Resonancia Magnética , Masculino , Radiografía , Ratas , Ratas Wistar , Estómago/efectos de los fármacosRESUMEN
Chemosensing of nutrients in the gastrointestinal tract plays physiologically important roles in the regulation of food intake behaviors, including digestion, absorption, metabolism and other subsequently occurring body functions via brain activation. Free amino acids, liberated from ingested foods, are of course essential nutrients which compose the body proteins and sometimes determine the taste of the food. Glutamate, one of the most abundant amino acids in the foods and the liberated free form, critically contributes to the 'umami' taste perception. Recently, it has been revealed that dietary glutamate has many beneficial functions in the gastrointestinal tract. However, the precise mechanism of glutamate sensing still remains unclear. Using primary rat gastric mucosal cell cultures, we demonstrated that somatostatin-secreting D cells are candidate cells for glutamate sensing in the stomach through inhibition of somatostatin release. Considering that somatostatin is one of the major negative regulators of gastric functions, it is suggested that some parts of glutamate's beneficial effects could be explained by suppression of the inhibitory somatostatin effects, i.e. stimulation, by glutamate.
Asunto(s)
Aminoácidos/farmacología , Mucosa Gástrica/citología , Mucosa Gástrica/metabolismo , Receptores Sensibles al Calcio/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Glutamato Metabotrópico/metabolismo , Células Secretoras de Somatostatina/efectos de los fármacos , Animales , Células Cultivadas , Ratas , Ratas Sprague-Dawley , Somatostatina/metabolismoRESUMEN
Monosodium L-glutamate (MSG) elicits a unique taste termed umami and is widely used as a flavor enhancer in various cuisines. In addition, recent studies suggest the existence of sensors for L-glutamate (Glu) and transduction molecules in the gut mucosa as well as in the oral cavity. The vagal gastric afferent responds specifically to the luminal stimulation of Glu in the stomach and regulates the autonomic reflexes. The intragastric infusion of Glu also activates several brain areas (insular cortex, limbic system, and hypothalamus) and is able to induce flavor-preference learning in rats. These results suggest that umami signaling via gustatory and visceral pathways plays an important role in the processes of digestion, absorption, metabolism, and other physiological functions via activation of the brain.
Asunto(s)
Encéfalo/fisiología , Fenómenos Fisiológicos del Sistema Digestivo , Ácido Glutámico/farmacología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Gusto/fisiología , Animales , Sistema Nervioso Autónomo/fisiología , Encéfalo/efectos de los fármacos , Alimentos , Humanos , Estómago/efectos de los fármacos , Estómago/fisiologíaRESUMEN
BACKGROUND: Dietary-free L-glutamate (Glu) in the stomach interacts with specific Glu receptors (T1R1/T1R3 and mGluR1-8) expressed on surface epithelial and gastric gland cells. Furthermore, luminal Glu activates the vagal afferents in the stomach through the paracrine cascade including nitric oxide and serotonin (5-HT). AIM: To elucidate the role of dietary Glu in neuroendocrine control of the gastrointestinal phase of gastric secretion. METHODS: In Pavlov or Heidenhain gastric pouch dogs, secretion was measured in the pouch while monosodium glutamate (MSG) was intubated into the main stomach alone or in combination with liquid diets. RESULTS: In both experimental models, supplementation of the amino acid-rich diet with MSG (100 mmol/l) enhanced secretions of acid, pepsinogen and fluid, and elevated plasma gastrin-17. However, MSG did not affect secretion stimulated by the carbohydrate-rich diet and had no effect on basal secretion when applied in aqueous solution. Effects of MSG were abolished by denervation of the stomach and proximal small intestine with intragastrically applied lidocaine and partially suppressed with the 5-HT(3) receptor blocker granisetron. CONCLUSIONS: Supplementation of amino acid-rich liquid diets with MSG enhances gastrointestinal phase secretion through neuroendocrine pathways which are partially mediated by 5-HT. Possible mechanisms are discussed.
Asunto(s)
Mucosa Gástrica/metabolismo , Glutamato de Sodio/farmacología , Estómago/efectos de los fármacos , Aminoácidos/farmacología , Animales , Dieta , Carbohidratos de la Dieta/farmacología , Perros , Femenino , Ácido Gástrico/metabolismo , Mucosa Gástrica/inervación , Gastrinas/sangre , Masculino , Modelos Teóricos , Sistemas Neurosecretores/fisiología , Pepsinógenos/metabolismo , Receptores de Serotonina 5-HT3/fisiología , Glutamato de Sodio/administración & dosificación , Estómago/inervación , Estómago/fisiologíaRESUMEN
BACKGROUND: Glucocorticoid (GC) treatment reportedly exaggerates renal fibrosis in progressive kidney diseases during which hypoxia occurs as an unavoidable consequence in renal tubular cells. Two major fibrotic factors, hypoxia and transforming growth factor-ß (TGF-ß), upregulate the production of plasminogen activator inhibitor-1 (PAI-1), a fibrosis enhancer. Most recently, we reported that GC increases PAI-1 production in human proximal tubular epithelial cells (HPTEC). However, the detailed interactions that occur between these PAI-1 inducers in HPTEC remain to be clarified. METHODS: Confluent HPTECs were treated with GC and/or TGF-ß for 24 h under normoxia or hypoxia. The mRNA and protein amounts of PAI-1 and GC receptor (GR) were determined by TaqMan quantitative PCR and immunoassays, respectively. GC and hypoxia response element (GRE and HRE) activities were measured by transient transfection of GRE- and HRE-luciferase expression vector. RESULTS: Hypoxia had no influence on dexamethasone (DXA)-enhanced GRE activity, as DXA had no influence on hypoxia-enhanced HRE activity. Hypoxia induced PAI-1 expression. TGF-ß increased basal and hypoxia-stimulated PAI-1 production. Hydrocortisone (HC) and DXA increased hypoxia- or TGF-ß-stimulated production of PAI-1 mRNA and protein. Moreover, DXA enhanced hypoxia plus TGF-ß-stimulated PAI-1 production. The PAI-1-increasing effect of HC under hypoxia was abolished completely by RU-486, a specific inhibitor of the GR, and largely by PP2, a specific inhibitor of the Src family of protein tyrosine kinases. CONCLUSION: Glucocorticoid induces hypoxia- and hypoxia plus TGF-ß-stimulated PAI-1 production via the GR and tyrosine kinase pathways. These actions of GC may partially explain the renal fibrotic changes seen in progressive inflammatory kidney diseases during GC treatment.
Asunto(s)
Glucocorticoides/farmacología , Hipoxia/metabolismo , Túbulos Renales Proximales/efectos de los fármacos , Túbulos Renales Proximales/metabolismo , Inhibidor 1 de Activador Plasminogénico/biosíntesis , Factor de Crecimiento Transformador beta1/farmacología , Células Cultivadas , Dexametasona/farmacología , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Túbulos Renales Proximales/citología , Túbulos Renales Proximales/patología , Proteínas Tirosina Quinasas/metabolismo , Receptores de Glucocorticoides/metabolismoRESUMEN
It is well known that the postingestive effect modulates subsequent food preference. We previously showed that monosodium L-glutamate (MSG) can increase flavor preference by its postingestive effect. The neural pathway involved in mediating this effect, however, remains unknown. We show here the role of the vagus nerve in acquiring this learned flavor preference and in the brain's response to intragastric glutamate infusion. Adult rats with an intragastric cannula underwent total abdominal branch vagotomies (TVX), common hepatic branch vagotomies (HVX), total abdominal branch vagotomies with the common hepatic branch intact (TVXh), or sham operations (Sham). Following recovery, rats were subjected to a conditioned flavor preference paradigm, in which they drank a flavored solution (CS+) paired with intragastric MSG or another flavored solution (CS-) paired with intragastric distilled water. After conditioning, the Sham and HVX groups demonstrated significantly higher intake of CS+ than CS-, whereas the TVXh and TVX groups showed no significant differences. We then conducted an fMRI study to identify the brain areas that responded to the intragastric glutamate in each group. In the Sham, HVX and TVXh groups, intragastric MSG significantly increased the BOLD intensity in the nucleus of the solitary tract. The amygdala, hippocampus and lateral hypothalamus were also activated in the Sham and HVX groups but not in the TVXh and TVX groups. These results indicate that the abdominal vagus nerve is necessary for acquiring preference and that the lateral hypothalamus and limbic system could be key areas for integrating the information on gut glutamate and oronasal stimuli.
Asunto(s)
Encéfalo/fisiología , Condicionamiento Clásico/fisiología , Preferencias Alimentarias/fisiología , Tracto Gastrointestinal/fisiología , Nervio Vago/fisiología , Animales , Encéfalo/irrigación sanguínea , Condicionamiento Clásico/efectos de los fármacos , Aromatizantes/farmacología , Tracto Gastrointestinal/efectos de los fármacos , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Masculino , Vías Nerviosas/fisiología , Oxígeno/sangre , Ratas , Ratas Sprague-Dawley , Glutamato de Sodio/farmacología , Gusto/fisiología , Vagotomía/métodosRESUMEN
BACKGROUND & AIMS: The gut-brain axis, which transmits nutrient information from the gastrointestinal tract to the brain, is important for the detection of dietary nutrients. We used functional magnetic resonance imaging of the rat forebrain to investigate how this pathway conveys nutrient information from the gastrointestinal tract to the brain. METHODS: We investigated the contribution of the vagus nerve by comparing changes of blood oxygenation level-dependent signals between 24 control rats and 22 rats that had undergone subdiaphragmatic vagotomy. Functional data were collected under alpha-chloralose anesthesia continuously 30 minutes before and 60 minutes after the start of intragastric infusion of L-glutamate or glucose. Plasma insulin, L-glutamate, and blood glucose levels were measured and compared with blood oxygenation level-dependent signals. RESULTS: Intragastric administration of L-glutamate or glucose induced activation in distinct forebrain regions, including the cortex, hypothalamus, and limbic areas, at different time points. Vagotomy strongly suppressed L-glutamate-induced activation in most parts of the forebrain. In contrast, vagotomy did not significantly affect brain activation induced by glucose. Instead, blood oxygenation level-dependent signals in the nucleus accumbens and amygdala, in response to gastrointestinal glucose, varied along with fluctuations of plasma insulin levels. CONCLUSIONS: These results indicate that the vagus nerve and insulin are important for signaling the presence of gastrointestinal nutrients to the rat forebrain. These signal pathways depend on the ingested nutrients.
Asunto(s)
Sistema Nervioso Entérico/metabolismo , Tracto Gastrointestinal/inervación , Glucosa/metabolismo , Prosencéfalo/metabolismo , Transducción de Señal , Glutamato de Sodio/metabolismo , Nervio Vago/metabolismo , Administración Oral , Animales , Glucemia/metabolismo , Mapeo Encefálico/métodos , Vaciamiento Gástrico , Tracto Gastrointestinal/metabolismo , Glucosa/administración & dosificación , Insulina/sangre , Imagen por Resonancia Magnética , Masculino , Prosencéfalo/anatomía & histología , Ratas , Ratas Sprague-Dawley , Glutamato de Sodio/administración & dosificación , Glutamato de Sodio/sangre , Factores de Tiempo , Vagotomía , Nervio Vago/cirugíaRESUMEN
Taste cells are chemosensory epithelial cells that sense distinct taste quality such as umami, sweet, bitter, sour and salty. Taste cells utilize G protein-coupled receptors to detect umami, sweet and bitter taste whereas ion channels are responsible for detecting salty and sour taste. Among these taste receptors, taste receptor type 2, T1R2 (or Tas1r2), has been identified as a sole sweet taste receptor in mammals that mediates sweet signals upon dimerization with T1R3. However, because of limited availability of reliable antibodies and low expression level of G protein-coupled receptors, it is uneasy to identify the cell-types that express these receptors in non-taste tissues. In this study, we have generated a T1R2-LacZ reporter knock-in mouse to investigate tissue distribution of T1R2 at a single-cell level. We found that the LacZ gene expression in these mice was faithful to the expression of T1R2 in the taste tissue and in the gastrointestinal tract where T1R3 expression has been reported. Surprisingly, T1R2 expression was also found in the testis. Mice homozygous for T1R2 deletion lacked T1R2 protein analyzed by the antibody raised against T1R2 peptide sequences. In summary, the T1R2 knock-in mouse is a powerful tool to analyze the putative targets for sweeteners as well as to study the physiological roles of T1R2 in detecting sugars.
Asunto(s)
Técnicas de Sustitución del Gen , Receptores Acoplados a Proteínas G/genética , Gusto/genética , beta-Galactosidasa/genética , Animales , Carbohidratos/farmacología , Tracto Gastrointestinal/metabolismo , Genes Reporteros , Masculino , Ratones , Ratones Mutantes , Receptores Acoplados a Proteínas G/fisiología , Eliminación de Secuencia , Edulcorantes/farmacología , Gusto/efectos de los fármacos , Testículo/metabolismoRESUMEN
Dietary free glutamate is known to elicit umami, one of the five basic tastes perceived via the specific taste sensor cells on the tongue. Recent studies suggest the specific glutamate sensors exist in the gastric mucosa and contribute to the regulation of gastrointestinal functions, yet the precise mechanism remains still unknown. We established the method to enrich various cell fractions from the isolated rat gastric mucosa and characterized the expression of putative glutamate sensors using such cell fractions. The gastric mucosal cell fractions such as surface mucous, parietal, chief, and endocrine cells were successfully prepared by mucosal protease digestion, elutriation, and gradient centrifugation. The characteristics of these cells were confirmed by real-time RT-PCR using the respective cell-specific markers. Parietal cell fraction exclusively expressed putative umami receptor molecules such as T1R1 and mGluR1 compared to other fractions, although the degree of expression was low. In contrast, the representative taste cell specific markers such as PLCbeta2 and TRPM5 were specifically expressed in the smaller endocrine cell fraction. Both parietal and smaller endocrine cell fractions also positively expressed some mGluR subtypes. The chief-cell fraction less expressed T1R1 and mGluR1. These results suggest that multiple glutamate sensors, probably different mechanisms from taste buds, contribute to the glutamate sensing in the gastric mucosa.
Asunto(s)
Mucosa Gástrica/citología , Mucosa Gástrica/metabolismo , Ácido Glutámico/metabolismo , Animales , Fraccionamiento Celular/métodos , Fraccionamiento Celular/tendencias , Mucosa Gástrica/efectos de los fármacos , Ácido Glutámico/farmacología , Células Parietales Gástricas/citología , Células Parietales Gástricas/efectos de los fármacos , Células Parietales Gástricas/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores de Glutamato/biosíntesisRESUMEN
Ammonia is one of the important toxins produced by Helicobacter pylori (H. pylori), the major cause of peptic ulcer diseases. We examined whether glutamine or marzulene (a gastroprotective drug containing 1% sodium azulene and 99% glutamine) protects the gastric mucosa against H. pylori in vivo and investigated the mechanism underlying glutamine-induced mucosal protection against ammonia in gastric epithelial cells in vitro. Mongolian gerbils were fed for 3 months with a diet containing glutamine (2%-20%) or marzulene (20%) starting from 2 weeks or 2 years after H. pylori infection. Then, gastric mucosal changes were evaluated both macro- and microscopically. Cultured gastric epithelial cells were incubated in the presence of ammonia, with or without glutamine; and cell viability, ammonia accumulation, and chemokine production were determined. Gerbils exhibited edema, congestion, and erosion after 3-month infection; and after 2-year infection, they showed cancer-like changes in the gastric mucosa. Glutamine and marzulene significantly suppressed these pathological changes caused in the gastric mucosa by H. pylori infection. Ammonia was accumulated in the cells, resulting in an increase in chemokine production and a decrease in cell viability. These pathological responses were prevented by glutamine. In addition, glutamine decreased chemokine production and cell death through inhibition of cellular accumulation of ammonia, resulting in the prevention of H. pylori-induced gastric diseases in vivo. These results suggest that glutamine/marzulene would be useful for prophylactic treatment of H. pylori-induced gastric diseases in patients.
Asunto(s)
Glutamina/administración & dosificación , Infecciones por Helicobacter/prevención & control , Helicobacter pylori/efectos de los fármacos , Gastropatías/prevención & control , Animales , Azulenos/administración & dosificación , Línea Celular Tumoral , Células Cultivadas , Combinación de Medicamentos , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/microbiología , Mucosa Gástrica/patología , Gerbillinae , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/patología , Helicobacter pylori/fisiología , Humanos , Masculino , Ratas , Gastropatías/microbiología , Gastropatías/patologíaRESUMEN
Some ingested nutrients have postingestive effects that modulate food intake and improve mood subconsciously. Here, we provide an overview of the positive postingestive effects of such nutrients, primarily L-glutamate, sugar, and lipids, with respect to behavior and brain function. We also discuss the mechanisms of brain activation resulting from signaling through the gut-brain axis. Recent studies have shown that rats prefer solutions paired with intragastric nutrients that have positive postingestive effects. Using functional magnetic resonance imaging (fMRI), we previously evaluated neural activation in response to ingested glucose, L-glutamate, and corn oil emulsion in rats and found that distinct forebrain regions were activated by these nutrients. Most of the areas activated by intragastric administration of L-glutamate were eliminated by abdominal vagotomy. On the other hand, the areas activated by intragastric administration of glucose were not affected by vagotomy. A behavioral study showed similar results for L-glutamate and glucose. These results indicate that brain activation in response to ingested nutrients occurs through distinct internal signals from the gut to the brain. Distinct regional and temporal activation in the brain determines the variety of postingestive behaviors and physiological responses.