Tongue Leptin Decreases Oro-Sensory Perception of Dietary Fatty Acids

Leptin, an anorectic hormone, regulates food intake, energy expenditure and body weight. We assessed the implication of tongue leptin in the modulation of oro-sensory detection of dietary fatty acids in mice. The RT-PCR analysis showed that mRNA encoding leptin and leptin receptor (Ob-Rb) was expressed in mice taste bud cells (TBC). Confocal microscopic studies showed that the lipid sensor CD36 was co-expressed with leptin in mice TBC. Silencing of leptin or Ob-Rb mRNA in tongue papillae upregulated preference for a long-chain fatty acid (LCFA), i.e., linoleic acid (LA), in a two-bottle paradigm in mice. Furthermore, tongue leptin application decreased the preference for the LCFA. These results suggest that tongue leptin exerts an inhibitory action on fatty acid preference. In isolated mice TBC, leptin decreased LCFA-induced increases in free intracellular calcium concentrations, [Ca2+]i. Leptin and LCFA induced the phosphorylation of ERK1/2 and STAT-3 and there were no additive or opposite effects of the two agents on the degree of phosphorylation. However, leptin, but not the LCFA, induced phosphoinositide-3-kinase (PI-3-K)-dependent Akt phosphorylation in TBC. Furthermore, leptin induced hyperpolarization, whereas LCFA induced depolarization in TBC. Our study demonstrates that tongue leptin exerts an inhibitory action on oro-sensory detection of a dietary fatty acid by interfering with Ca2+ signaling and membrane potential in mice TBC.

Increased Fat Taste Preference in Progranulin-Deficient Mice

Progranulin deficiency in mice is associated with deregulations of the scavenger receptor signaling of CD36/SCARB3 in immune disease models, and CD36 is a dominant receptor in taste bud cells in the tongue and contributes to the sensation of dietary fats. Progranulin-deficient mice (Grn−/−) are moderately overweight during middle age. We therefore asked if there was a connection between progranulin/CD36 in the tongue and fat taste preferences. By using unbiased behavioral analyses in IntelliCages and Phenomaster cages we showed that progranulin-deficient mice (Grn−/−) developed a strong preference of fat taste in the form of 2% milk as opposed to 0.3% milk, and for diluted MCTs versus tap water. The fat preference in the 7d-IntelliCage observation period caused an increase of 10% in the body weight of Grn−/− mice, which did not occur in the wildtype controls. CD36 expression in taste buds was reduced in Grn−/− mice at RNA and histology levels. There were no differences in the plasma or tongue lipids of various classes including sphingolipids, ceramides and endocannabinoids. The data suggest that progranulin deficiency leads to a lower expression of CD36 in the tongue resulting in a stronger urge for fatty taste and fatty nutrition.

Preparation and application of taste bud organoids in biomedicine towards chemical sensation mechanisms

Taste is one of the most basic and important sensations that is able to monitor the food quality and avoid intake of potential danger materials. Whether as an inevitable symptom of aging or a complication of cancer treatment, taste loss so seriously affects the patient’s life quality. Taste bud organoids provide a great convenience for the research of taste functions and the underlying mechanisms due to their characteristics of availability, strong maneuverability, and high similarity to the in-vivo taste buds. This review gives a systemic and comprehensive introduction to the preparation and application of taste bud organoids towards chemical sensing mechanisms. For the first, the basic structure and function of taste buds in biomedicine will be brief introduced. Then, the currently available approaches for the preparation of taste bud organoids are summarized and discussed, which are mainly divided into two categories, i.e. stem/progenitor cell-derived approach and tissue-derived approach. For the next, different applications of taste bud organoids in biomedicine are outlined based on their central roles such as disease modeling, biological sensing, gene regulation, and signal transduction. Finally, the current challenges, future development trends and prospects of research in taste bud organoids are proposed and discussed.

Additive Effects of L-Ornithine on Preferences to Basic Taste Solutions in Mice

In addition to the taste receptors corresponding to the six basic taste qualities—sweet, salty, sour, bitter, umami, and fatty—another type of taste receptor, calcium-sensing receptor (CaSR), is found in taste-bud cells. CaSR is called the ‘kokumi’ receptor because its agonists increase sweet, salty and umami tastes to induce ‘koku’, a Japanese word meaning the enhancement of flavor characters such as thickness, mouthfulness, and continuity. Koku is an important factor for enhancing food palatability. However, it is not well known whether other kokumi-receptors and substances exist. Here, we show that ornithine (L-ornithine but not D-ornithine) at low concentrations that do not elicit a taste of its own, enhances preferences to sweet, salty, umami, and fat taste solutions in mice. Increased preference to monosodium glutamate (MSG) was the most dominant effect. Antagonists of G-protein-coupled receptor family C group 6 subtype A (GPRC6A) abolished the additive effect of ornithine on MSG solutions. The additive effects of ornithine on taste stimuli are thought to occur in the oral cavity, and are not considered post-oral events because ornithine’s effects were confirmed in a brief-exposure test. Moreover, the additive effects of ornithine and the action of the antagonist were verified in electrophysiological taste nerve responses. Immunohistochemical analysis implied that GPRC6A was expressed in subsets of type II and type III taste cells of mouse circumvallate papillae. These results are in good agreement with those reported for taste modulation involving CaSR and its agonists. The present study suggests that ornithine is a kokumi substance and GPRC6A is a newly identified kokumi receptor.

An update on extra-oral bitter taste receptors

Bitter taste-sensing type 2 receptors (TAS2Rs or T2Rs), belonging to the subgroup of family A G-protein coupled receptors (GPCRs), are of crucial importance in the perception of bitterness. Although in the first instance, TAS2Rs were considered to be exclusively distributed in the apical microvilli of taste bud cells, numerous studies have detected these sensory receptor proteins in several extra-oral tissues, such as in pancreatic or ovarian tissues, as well as in their corresponding malignancies. Critical points of extra-oral TAS2Rs biology, such as their structure, roles, signaling transduction pathways, extensive mutational polymorphism, and molecular evolution, have been currently broadly studied. The TAS2R cascade, for instance, has been recently considered to be a pivotal modulator of a number of (patho)physiological processes, including adipogenesis or carcinogenesis. The latest advances in taste receptor biology further raise the possibility of utilizing TAS2Rs as a therapeutic target or as an informative index to predict treatment responses in various disorders. Thus, the focus of this review is to provide an update on the expression and molecular basis of TAS2Rs functions in distinct extra-oral tissues in health and disease. We shall also discuss the therapeutic potential of novel TAS2Rs targets, which are appealing due to their ligand selectivity, expression pattern, or pharmacological profiles.

Novel, Fully Characterised Bovine Taste Bud Cells of Fungiform Papillae

Current understanding of functional characteristics and biochemical pathways in taste bud cells have been hindered due the lack of long-term cultured cells. To address this, we developed a holistic approach to fully characterise long term cultured bovine taste bud cells (BTBCs). Initially, cultured BTBCs were characterised using RT-PCR gene expression profiling, immunocytochemistry, flowcytometry and calcium imaging, that confirmed the cells were mature TBCs that express taste receptor genes, taste specific protein markers and capable of responding to taste stimuli, i.e., denatonium (2 mM) and quinine (462.30 μM). Gene expression analysis of forty-two genes implicated in taste transduction pathway (map04742) using custom-made RT-qPCR array revealed high and low expressed genes in BTBCs. Preliminary datamining and bioinformatics demonstrated that the bovine α-gustducin, gustatory G-protein, have higher sequence similarity to the human orthologue compared to rodents. Therefore, results from this work will replace animal experimentation and provide surrogate cell-based throughput system to study human taste transduction.

Sprague Dawley Rats Gaining Weight on a High Energy Diet Exhibit Damage to Taste Tissue Even after Return to a Healthy Diet

Many reports detail taste dysfunction in humans and animals with obesity. For example, mice consuming an obesogenic diet for a short period have fewer taste buds than their lean littermates. Further, rats with diet-induced obesity (DIO) show blunted electrophysiological responses to taste in the brainstem. Here, we studied the effects of high energy diet (HED)-induced peripheral taste damage in rats, and whether this deficiency could be reversed by returning to a regular chow diet. Separate groups of rats consumed a standard chow diet (Chow), a HED for 10 weeks followed by a return to chow (HED/chow), or a HED for 10 weeks followed by a restricted HED that was isocaloric with consumption by the HED/chow group (HED/isocal). Fungiform taste papilla (FP) and circumvallate taste bud abundance were quantified several months after HED groups switched diets. Results showed that both HED/chow and HED/isocal rats had significantly fewer FP and lower CV taste bud abundance than control rats fed only chow. Neutrophil infiltration into taste tissues was also quantified, but did not vary with treatment on this timeline. Finally, the number of cells undergoing programmed cell death, measured with caspase-3 staining, inversely correlated with taste bud counts, suggesting taste buds may be lost to apoptosis as a potential mechanism for the taste dysfunction observed in obesity. Collectively, these data show that DIO has lasting deleterious effects on the peripheral taste system, despite a change from a HED to a healthy diet, underscoring the idea that obesity rather than diet predicts damage to the taste system.

Does intervention with GLP-1 receptor agonist semaglutide modulate perception of sweet taste in women with obesity: study protocol of a randomized, single-blinded, placebo-controlled clinical trial

Background Preclinical studies demonstrated that glucagon-like peptide 1 (GLP-1) is locally synthesized in taste bud cells and that GLP-1 receptor exists on the gustatory nerves in close proximity to GLP-1-containing taste bud cells. This local paracrine GLP-1 signalling seems to be specifically involved in the perception of sweets. However, the role of GLP-1 in taste perception remains largely unaddressed in clinical studies. Whether any weight-reducing effects of GLP-1 receptor agonists are mediated through the modulation of taste perception is currently unknown. Methods and analysis This is an investigator-initiated, randomized single-blind, placebo-controlled clinical trial. We will enrol 30 women with obesity and polycystic ovary syndrome (PCOS). Participants will be randomized in a 1:1 ratio to either semaglutide 1.0 mg or placebo for 16 weeks. The primary endpoints are alteration of transcriptomic profile of tongue tissue as changes in expression level from baseline to follow-up after 16 weeks of treatment, measured by RNA sequencing, and change in taste sensitivity as detected by chemical gustometry. Secondary endpoints include change in neural response to visual food cues and to sweet-tasting substances as assessed by functional MRI, change in body weight, change in fat mass and change in eating behaviour and food intake. Discussion This is the first study to investigate the role of semaglutide on taste perception, along with a neural response to visual food cues in reward processing regions. The study may identify the tongue and the taste perception as a novel target for GLP-1 receptor agonists. Ethics and disseminations The study has been approved by the Slovene National Medical Ethics Committee and will be conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. Results will be submitted for publication in an international peer-reviewed scientific journal. Trial registration ClinicalTrials.govNCT04263415. Retrospectively registered on 10 February 2020