暂无摘要。

Retinal sensitivity to a variety of artificial sweeteners was tested by monitoring changes in internal free calcium in isolated retinal neurons using Fluo3. Several ligands, including aspartame and saccharin elevated internal free calcium. The effects of these ligands were mediated by both ligand-gated membrane channels and G-protein coupled receptors. We explored the receptors responsible for this phenomenon. Surprisingly, mRNA for subunits of the sweet taste receptor dimer (T1R2 and T1R3) were found in retina. Interestingly, knockdown of T1R2 reduced the response to saccharin but not aspartame. But TRPV1 channel antagonists suppressed the responses to aspartame. The results indicate that artificial sweeteners can increase internal free calcium in the retinal neurons through multiple pathways. Furthermore, aspartame reduced the b-wave, but not the a-wave, of the electroretinogram, indicating disruption of communication between photoreceptors and second order neurons.

OBJECTIVE: Poorly controlled diabetes frequently exacerbates lung infection, thereby complicating treatment strategies. Recent studies have shown that exendin-4 exhibits not only hypoglycemic but also anti-inflammatory properties. This study aimed to explore the role of exendin-4 in lung infection with diabetes, as well as its association with NOD1/NF-κB and the T1R2/T1R3 sweet taste receptor.
METHODS: 16HBE human bronchial epithelial cells cultured with 20 mM glucose were stimulated with lipopolysaccharide (LPS) isolated from Pseudomonas aeruginosa (PA). Furthermore, Sprague‒Dawley rats were fed a high-fat diet, followed by intraperitoneal injection of streptozotocin and intratracheal instillation of PA. The levels of TNF-α, IL-1β and IL-6 were evaluated using ELISAs and RT‒qPCR. The expression of T1R2, T1R3, NOD1 and NF-κB p65 was assayed using western blotting and immunofluorescence staining. Pathological changes in the lungs of the rats were observed using hematoxylin and eosin (H&E) staining.
RESULTS: At the same dose of LPS, the 20 mM glucose group produced more proinflammatory cytokines (TNF-α, IL-1β and IL-6) and had higher levels of T1R2, T1R3, NOD1 and NF-κB p65 than the normal control group (with 5.6 mM glucose). However, preintervention with exendin-4 significantly reduced the levels of the aforementioned proinflammatory cytokines and signaling molecules. Similarly, diabetic rats infected with PA exhibited increased levels of proinflammatory cytokines in their lungs and increased expression of T1R2, T1R3, NOD1 and NF-κB p65, and these effects were reversed by exendin-4.
CONCLUSIONS: Diabetic hyperglycemia can exacerbate inflammation during lung infection, promote the increase in NOD1/NF-κB, and promote T1R2/T1R3. Exendin-4 can ameliorate PA-related pneumonia with diabetes and overexpression of NOD1/NF-κB. Additionally, exendin-4 suppresses T1R2/T1R3, potentially through its hypoglycemic effect or through a direct mechanism. The correlation between heightened expression of T1R2/T1R3 and an intensified inflammatory response in lung infection with diabetes requires further investigation.

Enteroendocrine cells (EECs) and vagal afferent neurons constitute functional sensory units of the gut, which have been implicated in bottom-up modulation of brain functions. Sodium oligomannate (GV-971) has been shown to improve cognitive functions in murine models of Alzheimer\'s disease (AD) and recently approved for the treatment of AD patients in China. In this study, we explored whether activation of the EECs-vagal afferent pathways was involved in the therapeutic effects of GV-971. We found that an enteroendocrine cell line RIN-14B displayed spontaneous calcium oscillations due to TRPA1-mediated calcium entry; perfusion of GV-971 (50, 100 mg/L) concentration-dependently enhanced the calcium oscillations in EECs. In ex vivo murine jejunum preparation, intraluminal infusion of GV-971 (500 mg/L) significantly increased the spontaneous and distension-induced discharge rate of the vagal afferent nerves. In wild-type mice, administration of GV-971 (100 mg· kg-1 ·d-1, i.g. for 7 days) significantly elevated serum serotonin and CCK levels and increased jejunal afferent nerve activity. In 7-month-old APP/PS1 mice, administration of GV-971 for 12 weeks significantly increased jejunal afferent nerve activity and improved the cognitive deficits in behavioral tests. Sweet taste receptor inhibitor Lactisole (0.5 mM) and the TRPA1 channel blocker HC-030031 (10 µM) negated the effects of GV-971 on calcium oscillations in RIN-14B cells as well as on jejunal afferent nerve activity. In APP/PS1 mice, co-administration of Lactisole (30 mg ·kg-1 ·d-1, i.g. for 12 weeks) attenuated the effects of GV-971 on serum serotonin and CCK levels, vagal afferent firing, and cognitive behaviors. We conclude that GV-971 activates sweet taste receptors and TRPA1, either directly or indirectly, to enhance calcium entry in enteroendocrine cells, resulting in increased CCK and 5-HT release and consequent increase of vagal afferent activity. GV-971 might activate the EECs-vagal afferent pathways to modulate cognitive functions.

This article, the second in a two-part series, continues the discussion on the nature of the relationship between the level of sweet taste suppression and eating behaviour, but in animal rather human subjects. In particular, the aim was to review the scientific literature on the impact that bioactive compounds that decrease oral sweet sensations have on intake, preference and physiological status in preclinical studies. This review was registered in the International Prospective Register of Systematic Reviews and conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Scottish Intercollegiate Guidelines Network and covered original papers included in Web of Science, PubMed, Scopus, Food Science Source and Food Science and technology abstracts. We identified 28 peer-reviewed English-language studies that fit the topic and met the inclusion criteria. We identified three plant species, Gymnema sylvestre, Hovenia dulcis, and Ziziphus jujuba, that possess acute sweetness-inhibitory properties. When administered orally, these plants reduced neural responses to sweet stimuli and decreased consumption. However, studies on the longer-term effects of antisweet activity remain to be conducted. Translating the valuable insights into the mechanisms underlying the relationship between sweet taste impairment and eating behaviour into practical clinical applications are discussed.

The taste of food plays a crucial role in determining what and how much we eat. Thus, interventions that temporarily block sweet taste receptors offer a promising approach to addressing unhealthy behaviours associated with sugary foods. However, the relationship between reduced sweet taste response and food consumption remains unclear, with contradictory findings. Certain studies suggest that a diminished perception of sweetness leads to a sense of fullness and results in reduced food intake, while others suggest the opposite effect. To shed some light, our systematic review looked into the relationship between diminished sweet taste response and food consumption by examining the effects of bioactive compounds that experimentally inhibit sweetness in healthy individuals. This review was registered in the International Prospective Register of Systematic Reviews and conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Scottish Intercollegiate Guidelines Network, and covered original papers included in Web of Science, PubMed, Scopus, Food Science Source and Food Science and technology abstracts. We identified 33 peer-reviewed English-language studies that fit the topic and met the inclusion criteria. The current literature predominantly focuses on the immediate impact of oral gymnemic acids, failing to provide preliminary evidence in support of the specific threshold hypothesis, above which food consumption decreases and below which the opposite effect occurs. Additionally, there was inconsistency in the findings regarding the short-term desire to eat following sweetness inhibition. Considering the downstream effects on energy intake and their clinical applications, further research is needed to clarify both the acute within-session effects (i.e., not wanting any more now) and the longer-term effects (i.e., deciding not to start eating) linked to oral sweet-taste-suppressing compounds.

Sweetness is a crucial indicator for identifying sweeteners used for flavor regulation and nutritional matching of foods. This study established a new quantitative sweetness evaluation method based on a combination of transiently transfected sweet taste receptor cells (STRs) and human sensory evaluation. Here, nine different sweeteners were evaluated and 10 sensory difference intensities and their corresponding concentrations were obtained through sensory evaluation. Using the same concentration solution as in the sensory evaluation, the dosage-response curve and EC50 of the nine sweeteners were obtained by analyzing the intracellular calcium signal fluctuation of STRs. Data analysis revealed that the calcium signal intensity and sweetness intensity under the same concentration of sweetener presented a strong linear correlation (R2 > 0.9). Additionally, we found a favorable correlation (R2 = 0.8746) between the relative sweetness and EC50. These findings indicate that the quantitative evaluation of sweetness based on STRs could be a potential alternative to human sensory evaluation.

Neohesperidin dihydrochalcone (NHDC) is a sweetener, which interacts with the transmembrane domain (TMD) of the T1R3 subunit of the human sweet taste receptor. Although NHDC and a sweet taste inhibitor lactisole share similar structural motifs, they have opposite effects on the receptor. This study involved the creation of an NHDC-docked model of T1R3 TMD through mutational analyses followed by in silico simulations. When certain NHDC derivatives were docked to the model, His7345.44 was demonstrated to play a crucial role in activating T1R3 TMD. The NHDC-docked model was then compared with a lactisole-docked inactive form, several residues were characterized as important for the recognition of NHDC; however, most of them were distinct from those of lactisole. Residues such as His6413.33 and Gln7947.38 were found to be oriented differently. This study provides useful information that will facilitate the design of sweeteners and inhibitors that interact with T1R3 TMD.

Long-term consumption of a high-sugar diet may contribute to the pathogenesis of several chronic diseases, such as obesity and type 2 diabetes. Sweet peptides derived from a wide range of food sources can enhance sweet taste without compromising the sensory properties. Therefore, the research and application of sweet peptides are promising strategies for reducing sugar consumption. This work first outlined the necessity for global sugar reduction, followed by the introduction of sweet taste receptors and their associated transduction mechanisms. Subsequently, recent research progress in sweet peptides from different protein sources was summarized. Furthermore, the main methods for the preparation and evaluation of sweet peptides were presented. In addition, the current challenges and potential applications are also discussed. Sweet peptides can stimulate sweetness perception by binding sweet taste receptors T1R2 and T1R3 in taste buds, which is an effective strategy for reducing sugar consumption. At present, sweet peptides are mainly prepared artificially by synthesis, hydrolysis, microbial fermentation, and bioengineering strategies. Furthermore, sensory evaluation, electronic tongues, and cell models have been used to assess the sweet taste intensity. The present review can provide a theoretical reference for reducing sugar consumption with the aid of sweet peptides in the food industry.

The sweet taste receptor (STR) is a G protein-coupled receptor (GPCR) responsible for mediating cellular responses to sweet stimuli. Early evidence suggests that elements of the STR signaling system are present beyond the tongue in metabolically active tissues, where it may act as an extraoral glucose sensor. This study aimed to delineate expression of the STR in extraoral tissues using publicly available RNA-sequencing repositories. Gene expression data was mined for all genes implicated in the structure and function of the STR, and control genes including highly expressed metabolic genes in relevant tissues, other GPCRs and effector G proteins with physiological roles in metabolism, and other GPCRs with expression exclusively outside the metabolic tissues. Since the physiological role of the STR in extraoral tissues is likely related to glucose sensing, expression was then examined in diseases related to glucose-sensing impairment such as type 2 diabetes. An aggregate co-expression network was then generated to precisely determine co-expression patterns among the STR genes in these tissues. We found that STR gene expression was negligible in human pancreatic and adipose tissues, and low in intestinal tissue. Genes encoding the STR did not show significant co-expression or connectivity with other functional genes in these tissues. In addition, STR expression was higher in mouse pancreatic and adipose tissues, and equivalent to human in intestinal tissue. Our results suggest that STR expression in mice is not representative of expression in humans, and the receptor is unlikely to be a promising extraoral target in human cardiometabolic disease.