Modelling of salt intake reduction by incorporation of umami substances into Japanese foods: a cross-sectional study.

BACKGROUND: Evidence has demonstrated that excess sodium intake is associated with development of several non-communicable diseases. The main source of sodium is salt. Therefore, reducing salt intake in foods is an important global public health effort to achieve sodium reduction and improve health. This study aimed to model salt intake reduction with 'umami' substances among Japanese adults. The umami substances considered in this study include glutamate or monosodium glutamates (MSG), calcium diglutamate (CDG), inosinate, and guanylate. METHODS: A total of 21,805 participants aged 57.8 years on average from the National Health and Nutrition Survey was used in the analysis. First, we employed a multivariable linear regression approach with overall salt intake (g/day) as a dependent variable, adjusting for food items and other covariates to estimate the contribution of salt intake from each food item that was selected through an extensive literature review. Assuming the participants already consume low-sodium products, we considered three scenarios in which salt intake could be reduced with the additional umami substances up to 30%, 60% and 100%. We estimated the total amount of population-level salt reduction for each scenario by age and gender. Under the 100% scenario, the Japan's achievement rates against the national and global salt intake reduction goals were also calculated. RESULTS: Without compromising the taste, the 100% or universal incorporation of umami substances into food items reduced the salt intake of Japanese adults by 12.8-22.3% at the population-level average, which is equivalent to 1.27-2.22 g of salt reduction. The universal incorporation of umami substances into food items changed daily mean salt intake of the total population from 9.95 g to 7.73 g: 10.83 g to 8.40 g for men and 9.21 g to 7.17 g for women, respectively. This study suggested that approximately 60% of Japanese adults could achieve the national dietary goal of 8 g/day, while only 7.6% would meet the global recommendation of 5.0 g/day. CONCLUSIONS: Our study provides essential information on the potential salt reduction with umami substances. The universal incorporation of umami substances into food items would enable the Japanese to achieve the national dietary goal. However, the reduced salt intake level still falls short of the global dietary recommendation.

Salt intake reduction using umami substance-incorporated food: a secondary analysis of NHANES 2017-2018 data.

OBJECTIVE: Excessive salt intake raises blood pressure and increases the risk of non-communicable diseases (NCD), such as CVD, chronic kidney disease and stomach cancer. Reducing the Na content of food is an important public health measure to control the NCD. This study quantifies the amount of salt reduced by using umami substances, i.e. glutamate, inosinate and guanylate, for adults in the USA. DESIGN: The secondary data analysis was performed using data of the US nationally representative cross-sectional dietary survey, the National Health and Nutrition Examination Survey (NHANES) 2017-2018. Per capita daily salt intake corresponding to the NHANES food groups was calculated in the four hypothetical scenarios of 0 %, 30 %, 60 % and 90 % market share of low-Na foods in the country. The salt reduction rates by using umami substances were estimated based on the previous study results. SETTING: The USA. PARTICIPANTS: 4139 individuals aged 20 years and older in the USA. RESULTS: Replacing salt with umami substances could help the US adults reduce salt intake by 7·31-13·53 % (7·50-13·61 % for women and 7·18-13·53 % for men), which is equivalent to 0·61-1·13 g/d (0·54-0·98 g/d for women and 0·69-1·30 g/d for men) without compromising the taste. Approximately, 21·21-26·04 % of the US adults could keep their salt intake below 5 g/d, the WHO's recommendation in the scenario where there is no low-Na product on the market. CONCLUSIONS: This study provides essential information that the use of umami substances as a substitute for salt may help reduce the US adults' salt intake.

Prediction of disability-adjusted life years for diseases due to low fruit intake in 2017-2040 in Japan.

OBJECTIVE: The current study aimed to predict disability-adjusted life years (DALY) rate in Japan through 2040 with plausible future scenarios of fruit intake for neoplasms, cardiovascular diseases (CVD) and diabetes and kidney diseases (DKD). DESIGN: Data from National Health and Nutrition Surveys and the Global Burden of Diseases study in 2017 were used. We developed an autoregressive integrated moving average model with four future scenarios. Reference scenario maintains the current trend. Best scenario assumes that the goal defined in Health Japan 21 is achieved in 2023 and is kept constant afterwards. Moderate scenario assumes that the goal is achieved in 2040. Constant scenario applies the same proportion of 2016 for the period between 2017 and 2040. SETTING: DALY rates in Japan were predicted for the period between 2017 and 2040. PARTICIPANTS: Population aged more than than 20 years old. RESULTS: In our reference forecast, the DALY rates in all-ages group were projected to be stable for CVD and continue increasing for neoplasms and DKD. Age group-specific DALY rates for these three disease groups were forecasted to decrease, with some exceptions. Among men aged 20-49 years, DALY attributable to CVD differed substantially between the scenarios, implying that there is a significant potential for reducing the burden of CVD by increasing fruit intake at the population level. CONCLUSIONS: Our scenario analysis shows that higher fruit intake is associated with lower disease burden in Japan. Further research is required to assess which policies and interventions can be used to achieve an increase in fruit intake as modelled in the scenarios of the current study.

Projections of disability-adjusted life years for major diseases due to a change in vegetable intake in 2017-2040 in Japan.

BACKGROUND: Low vegetable intake is one of the key dietary risk factors known to be associated with a range of health problems, including cardiovascular diseases (CVDs), cancer, and diabetes and kidney diseases (DKDs). Using data from Japan's National Health and Nutrition Surveys and the Global Burden of Diseases study in 2017, this study aimed to forecast the impact of change in vegetable intake on disability-adjusted life years (DALYs) between 2017 and 2040 for three diseases. METHODS: We generated a three-component model of cause-specific DALYs, including changes in major behavioural and metabolic risk predictors, the socio-demographic index and an autoregressive integrated moving average model to project future DALY rates for 2017-2040 using the data between 1990 and 2016. Data on Vegetable consumption and risk predictors, and DALY rate were obtained from Japan's National Health and Nutrition Surveys and the Global Burden of Diseases Study in 2017. We also modelled three scenarios of better, moderate and worse cases to evaluate the impact of change in vegetable consumption on the DALY rates for three diseases (CVDs, cancer, and DKDs). RESULTS: Projected mean vegetable intake in the total population showed a decreasing trend through 2040 to 237.7 g/day. A significant difference between the reference scenario and the better case scenario was observed with un-overlapped 95% prediction intervals of DALY rates in females aged 20-49 years (- 8.0%) for CVDs, the total population for cancer (- 5.6%), and in males (- 8.2%) and females (- 13.7%) for DKDs. CONCLUSIONS: Our analysis indicates that increased vegetable consumption would have a significant reduction in the burdens of CVDs, cancer and DKDs in Japan. By estimating the disease burden attributable to low vegetable intake under different scenarios of future vegetable consumption, our study can inform the design of targeted interventions for public health challenges.

Forecasting disability-adjusted life years for chronic diseases: reference and alternative scenarios of salt intake for 2017-2040 in Japan.

BACKGROUND: In Japan, a high-sodium diet is the most important dietary risk factor and is known to cause a range of health problems. This study aimed to forecast Japan's disability-adjusted life year (DALYs) for chronic diseases that would be associated with high-sodium diet in different future scenarios of salt intake. We modelled DALY forecast and alternative future scenarios of salt intake for cardiovascular diseases (CVDs), chronic kidney diseases (CKDs), and stomach cancer (SC) from 2017 to 2040. METHODS: We developed a three-component model of disease-specific DALYs: a component on the changes in major behavioural and metabolic risk predictors including salt intake; a component on the income per person, educational attainment, and total fertility rate under 25 years; and an autoregressive integrated moving average model to capture the unexplained component correlated over time. Data on risk predictors were obtained from Japan's National Health and Nutrition Surveys and from the Global Burden of Disease Study 2017. To generate a reference forecast of disease-specific DALY rates for 2017-2040, we modelled the three diseases using the data for 1990-2016. Additionally, we generated better, moderate, and worse scenarios to evaluate the impact of change in salt intake on the DALY rate for the diseases. RESULTS: In our reference forecast, the DALY rates across all ages were predicted to be stable for CVDs, continuously increasing for CKDs, and continuously decreasing for SC. Meanwhile, the age group-specific DALY rates for these three diseases were forecasted to decrease, with some exceptions. Except for the ≥70 age group, there were remarkable differences in DALY rates between scenarios, with the best scenario having the lowest DALY rates in 2040 for SC. This represents a wide scope of future trajectories by 2040 with a potential for tremendous decrease in SC burden. CONCLUSIONS: The gap between scenarios provides some quantification of the range of policy impacts on future trajectories of salt intake. Even though we do not yet know the policy mix used to achieve these scenarios, the result that there can be differences between scenarios means that policies today can have a significant impact on the future DALYs.

Correlation Between Activation of the Prelimbic Cortex, Basolateral Amygdala, and Agranular Insular Cortex During Taste Memory Formation.

Conditioned taste aversion (CTA) is a well-established learning paradigm, whereby animals associate tastes with subsequent visceral illness. The prelimbic cortex (PL) has been shown to be involved in the association of events separated by time. However, the nature of PL activity and its functional network in the whole brain during CTA learning remain unknown. Here, using awake functional magnetic resonance imaging and fiber tracking, we analyzed functional brain connectivity during the association of tastes and visceral illness. The blood oxygen level-dependent (BOLD) signal significantly increased in the PL after tastant and lithium chloride (LiCl) infusions. The BOLD signal in the PL significantly correlated with those in the amygdala and agranular insular cortex (IC), which we found were also structurally connected to the PL by fiber tracking. To precisely examine these data, we then performed double immunofluorescence with a neuronal activity marker (c-Fos) and an inhibitory neuron marker (GAD67) combined with a fluorescent retrograde tracer in the PL. During CTA learning, we found an increase in the activity of excitatory neurons in the basolateral amygdala (BLA) or agranular IC that project to the PL. Taken together, these findings clearly identify a role of synchronized PL, agranular IC, and BLA activity in CTA learning.

Involvement of multiple taste receptors in umami taste: analysis of gustatory nerve responses in metabotropic glutamate receptor 4 knockout mice.

KEY POINTS: The taste receptor T1R1 + T1R3 heterodimer and metabotropic glutamate receptors (mGluR) may function as umami taste receptors. Here, we used mGluR4 knockout (mGluR4-KO) mice and examined the function of mGluR4 in peripheral taste responses of mice. The mGluR4-KO mice showed reduced responses to glutamate and L-AP4 (mGluR4 agonist) in the chorda tympani and glossopharyngeal nerves without affecting responses to other taste stimuli. Residual glutamate responses in mGluR4-KO mice were suppressed by gurmarin (T1R3 blocker) and AIDA (group I mGluR antagonist). The present study not only provided functional evidence for the involvement of mGluR4 in umami taste responses, but also suggested contributions of T1R1 + T1R3 and mGluR1 receptors in glutamate responses. ABSTRACT: Umami taste is elicited by L-glutamate and some other amino acids and is thought to be initiated by G-protein-coupled receptors. Proposed umami receptors include heterodimers of taste receptor type 1, members 1 and 3 (T1R1 + T1R3), and metabotropic glutamate receptors 1 and 4 (mGluR1 and mGluR4). Accumulated evidences support the involvement of T1R1 + T1R3 in umami responses in mice. However, little is known about the in vivo function of mGluR in umami taste. Here, we examined taste responses of the chorda tympani (CT) and the glossopharyngeal (GL) nerves in wild-type mice and mice genetically lacking mGluR4 (mGluR4-KO). Our results indicated that compared to wild-type mice, mGluR4-KO mice showed significantly smaller gustatory nerve responses to glutamate and L-(+)-2-amino-4-phosphonobutyrate (an agonist for group III mGluR) in both the CT and GL nerves without affecting responses to other taste stimuli. Residual glutamate responses in mGluR4-KO mice were not affected by (RS)-alpha-cyclopropyl-4-phosphonophenylglycine (an antagonist for group III mGluR), but were suppressed by gurmarin (a T1R3 blocker) in the CT and (RS)-1-aminoindan-1,5-dicarboxylic acid (an antagonist for group I mGluR) in the CT and GL nerve. In wild-type mice, both quisqualic acid (an agonist for group I mGluR) and L-(+)-2-amino-4-phosphonobutyrate elicited gustatory nerve responses and these responses were suppressed by addition of (RS)-1-aminoindan-1,5-dicarboxylic acid and (RS)-alpha-cyclopropyl-4-phosphonophenylglycine, respectively. Collectively, the present study provided functional evidences for the involvement of mGluR4 in umami taste responses in mice. The results also suggest that T1R1 + T1R3 and mGluR1 are involved in umami taste responses in mice. Thus, umami taste would be mediated by multiple receptors.

Differences in BOLD responses to intragastrically infused glucose and saccharin in rats.

The postingestive effect is different between caloric and noncaloric sweeteners. The gut administration of glucose induces a preference for flavored water which is paired with the intragastric infusion of glucose. However, a comparison of the brain response to the gut glucose and saccharin stimuli still remains to be demonstrated. Here, using functional magnetic resonance imaging, we investigated the blood oxygenation level-dependent signal response to gut glucose and saccharin in the brain of conscious rats. Glucose induced a positive signal increase in the amygdala and nucleus accumben, both of which receive dopaminergic input from the ventral tegmental area. In contrast, saccharin administration did not activate these areas. Both glucose and saccharin increased the blood oxygenation level-dependent signal intensity in the insular cortex and the nucleus of the solitary tract. These results show that there were significant differences between postingestive glucose and saccharin-induced increases in the blood oxygenation level-dependent signal in rats. Together with previous findings, these results suggest distinct activation patterns in the brain for both glucose and saccharin, which is partially due to different changes of internal signals, including the blood glucose and insulin levels.

Dietary free L-glutamate contributes to maintaining a low sodium intake among Vietnamese.

Background: The World Health Organization (WHO) and the Food and Agriculture Organization (FAO) recommend the consumption of less than 2,000 mg of sodium/day to reduce blood pressure and the risk of conditions such as cardiovascular disease and coronary heart disease. The sodium intake among Vietnamese was reported to be 7,200 mg/d or more. Free L-glutamate enhances flavor when it is added to food and improves the taste of sodium-reduced foods. Objective: This study aims to investigate whether the intake of free L-glutamate-rich seasonings contributes to maintaining a low sodium intake in a cross-over study. Methods: From a total of 145 subjects, 42 participants were screened for participation in the cross-over design study. Subjects were randomly allocated to the Low free L-glutamate group (Low free L-Gl) and the Normal free L-glutamate group (Normal free L-Gl). Both received a direct educational guideline to reduce sodium intake. The Low free L-Gl group started with a restriction in the variety of free L-glutamate-rich seasonings, and the Normal free L-Gl group had no restriction in the variety of seasonings. Blood pressure was measured at week 0 (baseline), week 2, week 4, and week 6, while body weight, height, urine sodium and potassium excretion, chromogranin-A (CgA pmol/mg protein) from saliva, and free L-glutamate from food were measured at week 0, week 3, and week 6. Results: In Low free L-Gl, the amount of free L-glutamate in food decreased significantly from baseline to week 6 (p < 0.00), while it did not change in the Normal free L-Gl (p > 0.05). However, the reduction of sodium excretion at week 6 was 22% in Low free L-Gl (5,875 mg/d vs. 4,603 mg/d, p < 0.01) and 46% in Normal free L-Gl (6,107 mg/d vs. 3,277 mg/d, p < 0.00), both lower than the baseline. CgA (pmol/mg protein) did not show any difference between the two groups. Conclusion: The group with Normal free L-Gl intake showed a 46% reduction in sodium excretion by week 6 compared to the baseline. This suggests that the consumption of L-glutamate-rich seasonings when complemented with direct educational guidelines, can contribute to maintaining a low sodium intake.

Production of free glutamate in milk requires the leucine transporter LAT1.

The concentration of free glutamate (Glu) in rat's milk is ∼10 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.

Different TRPV1-mediated brain responses to intragastric infusion of capsaicin and capsiate.

Capsaicin and capsiate, which is an analogue of capsaicin, are agonists of capsaicin-binding transient potential vanilloid 1 (TRPV1) receptors. However, their physiological effects are different. Capsaicin induces thermogenesis and nociception, while the different kinetics of capsiate result in thermogenesis without nociception in the oral cavity. In the present study, using functional magnetic resonance imaging, we compared the brain activation after intragastric infusion of non-nociceptive levels of capsaicin and capsiate in wild-type and TRPV1-knockout (KO) mice. Capsaicin activated several brain regions, such as the periaqueductal grey (PAG), thalamic nuclei and hypothalamus, including the medial preoptic area (mPOA) and ventromedial hypothalamus (VMH). Most of these areas were not activated in TRPV1-KO mice. Capsiate activated several regions, including the thalamic nuclei, mPOA and VMH but not PAG in wild-type mice. Most of the activated areas were not activated by intragastric capsiate infusion in TRPV1-KO mice. These results demonstrate that TRPV1 is critical for the induction of activation in the hypothalamus by capsaicin and capsiate, and these distinct brain activations could help to explain the individual physiological reactions of capsaicin and capsiate.

Amino acid sensing in the gastrointestinal tract.

Rapid progress in gastroenterology during the first part of the last century has shown that gastrointestinal (GI) function is regulated by neuroendocrine, paracrine and endocrine signals. However, recent advances in chemical sensing, especially in the last decade, have revealed that free L-amino acids (AA), among other nutrients, play a critical role in modifying exocrine and endocrine secretion, modulating protein digestion, metabolism and nutrient utilization, and supporting the integrity and defense of the GI mucosa. Many of the mechanisms by which AAs elicit these functions in the GI has been linked to the traditional concept of hormone release and nervous system activation. But most these effects are not direct. AAs appear to function by binding to a chemical communication system such as G protein-coupled receptors (GPCRs) that activate signaling pathways. These intracellular signals, although their molecular bases are not completely elucidated yet, are the ones responsible for the neuronal activity and release of hormones that in turn regulate GI functions. This review aims to describe the distribution of the known GPCRs from the class 3 superfamily that bind to different kinds of AA, especially from the oropharyngeal cavity to the stomach, what kind of taste qualities they elicit, such as umami, bitter or sweet, and their activity in the GI tract.

Reversible brain response to an intragastric load of L-lysine under L-lysine depletion in conscious rats.

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.

Reducing salt intake with umami: A secondary analysis of data in the UK National Diet and Nutrition Survey.

Reducing sodium content in foods is an important public health measure to reduce salt intake and decrease the incidence of noncommunicable diseases, such as cardiovascular disease and chronic kidney disease. This study quantified the amount of salt intake that could potentially be reduced by using umami substances, including glutamate, inosinate, and guanylate, without compromising taste, for adults in the United Kingdom (UK). We used data comprised of 1834 adults aged 20 years and over from the National Diet and Nutrition Survey (NDNS RP) 2016/2017-2018/2019. Four hypothetical scenarios in which the market share of low-sodium foods accounts for 0%, 30%, 60%, or 90% of consumed products were considered in the analyses. Per capita daily salt intake corresponding to the NDNS RP food groups was calculated for each scenario, and the salt intake was aggregated by gender and age groups. Replacing salt with umami substances could help UK adults reduce daily salt intake by 9.09%-18.59% (9.21%-18.43% for women; 8.83%-19.43% for men), which is equivalent to 0.45-0.92 g/day of salt reduction (0.41-0.82 g/day for women; 0.50-1.10 g/day for men). The use of umami substances may serve as one method for the UK government to encourage salt intake reduction, particularly in the context of food product reformulation, as 80% of salt consumed in the country comes from processed foods. Empirical studies with sensory evaluation should be conducted to confirm consumer tolerance. The food industry should also be engaged in conversations regarding the addition of umami to food products in the United Kingdom.

Dietary free glutamate prevents diarrhoea during intra-gastric tube feeding in a rat model.

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.

Sense of taste in the gastrointestinal tract.

Recent advances in molecular biology have led to the investigation of the molecular mechanism by which chemicals such as odors and tastants are perceived by specific chemosensory organs. For example, G protein-coupled receptors expressed within the nasal epithelium and taste receptors in the oral cavity have been identified as odorant and taste receptors, respectively. However, there is much evidence to indicate that these chemosensory receptors are not restricted to primary chemosensory cells; they are also expressed and have function in other cells such as those in the airways and gastrointestinal (GI) tract. This short review describes the possible mechanisms by which taste signal transduction occurs in the oral cavity and tastants/nutrients are sensed in the GI tract by taste-like cells, mainly enteroendocrine and brush cells. Furthermore, it discusses the future perspectives of chemosensory studies.

New therapeutic strategy for amino acid medicine: effects of dietary glutamate on gut and brain function.

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.

Different BOLD responses to intragastric load of L-glutamate and inosine monophosphate in conscious rats.

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.

Luminal amino acid-sensing cells in gastric mucosa.

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.

Dietary glutamate signal evokes gastric juice excretion in dogs.

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.