Fat Taste Receptors Research Articles

Fat taste receptors and fatty milk in dolphins

Fat taste receptors and fatty milk in dolphins

FAHFA promotes intracellular calcium signaling via activating the fat taste receptor, CD36 and Src protein kinases in mice taste bud cells

Two lipid sensors, CD36 and GPR120, are crucial for the orosensory detection of fat taste and for mediating fat preference. However, the mechanism by which endogenous lipid (FAHFA) binds to CD36 to initiate intracellular signaling remains unexplained. Hence, the primary objective of this study is to investigate the binding mechanism of FAHFA to CD36 and its role in isolated mouse taste bud cells (mTBCs). The Schrodinger platform was used to assess the molecular dynamics of protein and ligand interactions, and an in vitro experiment was used to validate the findings. Based on the docking score of the ligand, the molecular mechanistic activities of the targeted complexes, CD36–5-POHSA (−8.2 kcal/mol), were investigated using the dynamic simulation. In comparison to linoleic acid (LA), POHSA rapidly increased [Ca2+]i via acting on CD36, and 5-POHSA treatment in mTBCs activated src-kinase at 20 μM. CD36 siRNA transfection in TBCs downregulate the CD36 protein expression as well as [Ca2+]i flux. This study suggests that 5-POHSA may help combat taste abnormalities and the adverse effects of obesity by binding to the lingual CD36 receptor and activating the tongue-brain axis.

Adiponectin Enhances Fatty Acid Signaling in Human Taste Cells by Increasing Surface Expression of CD36.

Adiponectin, a key metabolic hormone, is secreted into the circulation by fat cells where it enhances insulin sensitivity and stimulates glucose and fatty acid metabolism. Adiponectin receptors are highly expressed in the taste system; however, their effects and mechanisms of action in the modulation of gustatory function remain unclear. We utilized an immortalized human fungiform taste cell line (HuFF) to investigate the effect of AdipoRon, an adiponectin receptor agonist, on fatty acid-induced calcium responses. We showed that the fat taste receptors (CD36 and GPR120) and taste signaling molecules (Gα-gust, PLCβ2, and TRPM5) were expressed in HuFF cells. Calcium imaging studies showed that linoleic acid induced a dose-dependent calcium response in HuFF cells, and it was significantly reduced by the antagonists of CD36, GPR120, PLCβ2, and TRPM5. AdipoRon administration enhanced HuFF cell responses to fatty acids but not to a mixture of sweet, bitter, and umami tastants. This enhancement was inhibited by an irreversible CD36 antagonist and by an AMPK inhibitor but was not affected by a GPR120 antagonist. AdipoRon increased the phosphorylation of AMPK and the translocation of CD36 to the cell surface, which was eliminated by blocking AMPK. These results indicate that AdipoRon acts to increase cell surface CD36 in HuFF cells to selectively enhance their responses to fatty acids. This, in turn, is consistent with the ability of adiponectin receptor activity to alter taste cues associated with dietary fat intake.

Novel Fat Taste Receptor Agonists Curtail Progressive Weight Gain in Obese Male Mice

The spontaneous preference for dietary lipids is principally regulated by 2 lingual fat taste receptors, CD36 and GPR120. Obese animals and most of human subjects exhibit low orosensory perception of dietary fat because of malfunctioning of these taste receptors. Our aim was to target the 2 fat taste receptors by newly synthesized high affinity fatty acid agonists to decrease fat-rich food intake and obesity. We synthesized 2 fat taste receptor agonists (FTA), NKS-3 (CD36 agonist) and NKS-5 (CD36 and GPR120 agonist). We determined their molecular dynamic interactions with fat taste receptors and the effect on Ca2+ signaling in mouse and human taste bud cells (TBC). In C57Bl/6 male mice, we assessed their gustatory perception and effects of their lingual application on activation of tongue-gut loop. We elucidated their effects on obesity and its related parameters in male mice fed a high-fat diet. The two FTA, NKS-3 and NKS-5, triggered higher Ca2+ signaling than a dietary long-chain fatty acid in human and mouse TBC. Mice exhibited a gustatory attraction for these compounds. In conscious mice, the application of FTA onto the tongue papillae induced activation of tongue-gut loop, marked by the release of pancreato-bile juice into collecting duct and cholecystokinin and peptide YY into blood stream. Daily intake of NKS-3 or NKS-5 via feeding bottles decreased food intake and progressive weight gain in obese mice but not in control mice. Our results show that targeting fat sensors in the tongue by novel chemical fat taste agonists might represent a new strategy to reduce obesity.

The Visayan Warty Pig (Sus cebifrons) Genome Provides Insight Into Chromosome Evolution and Sensory Adaptation in Pigs.

It is largely unknown how mammalian genomes evolve under rapid speciation and environmental adaptation. An excellent model for understanding fast evolution is provided by the genus Sus, which diverged relatively recently and lacks postzygotic isolation. Here, we present a high-quality reference genome of the Visayan warty pig, which is specialized to a tropical island environment. Comparing the genome sequences and chromatin contact maps of the Visayan warty pig (Sus cebifrons) and domestic pig (Sus scrofa), we characterized the dynamics of chromosomal structure evolution during Sus speciation, revealing the similar chromosome conformation as the potential biological mechanism of frequent postdivergence hybridization among Suidae. We further investigated the different signatures of adaptive selection and domestication in Visayan warty pig and domestic pig with specific emphasize on the evolution of olfactory and gustatory genes, elucidating higher olfactory diversity in Visayan warty pig and positive and relaxed evolution of bitter and fat taste receptors, respectively, in domestic pig. Our comprehensive evolutionary and comparative genome analyses provide insight into the dynamics of genomes and how these change over relative short evolutionary times, as well as how these genomic differences encode for differences in the phenotypes.

Fat preference deficits and experience-induced recovery in global taste-deficient Trpm5 and Calhm1 knockout mice

There is much evidence that gustation mediates the preference for dietary fat in rodents. Several studies indicate that mice have fat taste receptors that activate downstream signaling elements, including TRPM5 and CALHM1 ion channels and P2×2/P2×3 purinergic gustatory nerve receptors. Experiment 1 further documented the involvement of TRPM5 in fat appetite by giving Trpm5 knockout (KO) mice, which show global taste deficits, 24-h two-bottle choice tests with ascending concentrations of soybean oil (0.1 - 10% Intralipid) vs. water. Unlike wildtype (WT) mice, naive Trpm5 KO mice were indifferent to 0.5 - 2.5% fat. They preferred 5–10% fat but consumed much less than WT mice. The same KO mice preferred all fat concentrations in a second test series, which is attributed to a postoral fat conditioned attraction to the non-taste flavor qualities of the Intralipid, although they consumed less fat than the WT mice. The fat preference deficits of the Trpm5 KO mice were as great or greater than those observed in Calhm1 KO mice, another KO line with global taste deficits. Experiment 2 examined experience-enhanced fat preferences in Trpm5 KO and Calhm1 KO mice by giving them one-bottle training with 1%, 2.5%, and 5% fat prior to two-bottle fat vs. water tests. The KO mice displayed increased two-bottle preferences for all concentrations, although they still consumed less 1% and 2.5% fat than WT mice. Thus, the postoral actions of fat induce robust preferences for fat in taste-deficient mice, but do not stimulate the high fat intakes observed in WT mice with normal fat taste signaling.

Single nucleotide polymorphism in CD36: Correlation to peptide YY levels in obese and non-obese adults

Human beings are often driven to exhibit dietary preference according to their hedonic characteristics. Though previous studies proposed that the fat taste preference of an obese individual was associated with BMI, the perception of fat taste differs for every individual. The genetic variation among populations in taste receptor genes such as CD36 may be a contributing factor for this difference. Satiety peptides can also play a role in the regulation of fat taste perception. Generally, this hormone helps us to feel the sense of satiety. We have analysed the relationship among oro-gustatory perception of dietary lipids, salivary peptide-YY and genetic polymorphism in CD36. Oral fatty acid sensitivity analysis was performed by alternative forced choice method. Salivary peptide-YY concentration was analysed by ELISA and single nucleotide polymorphism (SNP) in CD36 gene was determined by Real-Time PCR experiments. We observed that the SNP at rs1761667 of CD36 and oral detection threshold for linoleic acid (LA) are associated with choice of food, lipid profiles, peptide-YY as well as adiposity parameters in obese population. Obese peoples had significantly low levels of peptide YY than people with BMI less than 25. These factors possibly play a role in preference for energy rich diets, development of obesity and associated complications. This study provides a solid foundation for understanding the alterations in the dietary fat intake and levels of peptide-YY, which are associated with polymorphism in fat taste receptor. This is the first report that shows a significant relationship between the satiety hormone level, SNP in CD36 gene and oral fat detection threshold in human subjects.

Differential Effects of Continuous versus Intermittent Dietary Fat Intake on Markers of Serotonin Signaling in the Circumvallate Papillae of the Tongue

Taste is a primary sensory modality that guides organisms in their determination of food preferences. Previous studies suggest that orosensory fat sensing may contribute to the intake and preference of dietary fat leading to the development of obesity. CD36 is the proposed fat taste receptor on the circumvallate papillae (CV) of the tongue and mediates fat sensing. Fat signaling via CD36 on the CV involves the regulation of serotonin (5‐HT) in taste receptor cells and activation of gustatory afferent nerves. The aim of these experiments was to investigate the effects of dietary fat intake on 5‐HT signaling in the CV using two feeding paradigms: continuous access to high fat diet (HFD) vs. limited access to dietary fat. We hypothesized that consumption of dietary fat, in specific patterns, contributes to the decreased sensitivity (i.e. hyposensitivity) of fat sensing through 5‐HT signaling dysregulation. The first experiment investigated the effects of continuous access to either a HFD or a low fat diet (LFD) for 1, 3 or 14 days on 5‐HT signaling in the CV. The second experiment investigated the effects of limited daily and intermittent access to dietary fat on 5‐HT signaling in the CV. Body weight and kilocalorie intake were assessed. In the CV, expression levels of CD36, 5‐HT1A, SERT, TPH1, and TPH2 mRNA were determined by Real Time PCR. Continuous HFD consumption for 14 days increased CD36, 5‐HT1A and SERT mRNA expression on the CV, suggesting reduced lingual fat sensing via decreased gustatory signaling from taste receptor cells. Limited, daily access to dietary fat increased CD36 and TPH1 mRNA expression on the CV suggesting enhanced lingual fat sensing compared to chow fed controls. Limited, intermittent access to dietary led to an escalation of fat intake without significant alterations in lingual expression of 5‐HT signaling. These data suggest that different patterns of fat consumption differentially affect 5‐HT signaling in the CV and that continuous access to HFD may lead to decreased orosensory fat perception by altering 5‐HT signaling in taste receptors cells.Support or Funding InformationLSUHSC to SDPThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Taste perception and its effects on oral nutritional supplements in younger life phases.

The current review summarizes the importance of taste perception with regard to acceptance of oral nutritional supplements (ONS) in young children. We also shed light on how basic tastes may influence the orosensory detection of ONS in the light of genetic variations, encoding for different taste modalities, particularly for sweet and bitter (and fat), in children. Single nucleotide polymorphism (SNP) of bitter and sweet taste receptor genes, that is, respectively, TAS2R38 and T1R2/T1R3, may influence orosensory perception of 'bitter-made-sweet' ONS. The SNP of fat taste receptor gene, that is, CD36, might communicate with bitter taste perception. The emerging new sixth fat taste may interfere with obesity in children. Sweet and bitter taste modalities are innate cues, expressed by children from birth to adolescence, either by a strong preference or by food aversion. Sweet and bitter tastes also communicate with each other as sweeteners can mask bitter phenotype. The fat preference, encoded by specific lingual taste receptors, is also modulated, via its interaction with phenotype and genotype, by bitter taste. Sodium salts might interact with bitter taste. Finally, the taste modalities will impact on the intake of ONS in children as the taste phenotype changes in this population, irrespective to genotype.

Oleanolic acid improves diet-induced obesity by modulating fat preference and inflammation in mice

Obesity, triggered by high-fat diet (HFD), is associated to altered gustatory perception of dietary lipids. Oleanolic acid (OLA), a triterpene, has been reported to exert anti-obesity effects in animal models. Hence, we investigated the role of OLA in the modulation of oro-sensory perception of lipids in control and HFD-induced obese mice. As expected, OLA-treated obese mice exhibited a decrease in body, liver, and visceral adipose tissue weights. OLA treatment improved glucose tolerance, insulin level, plasma lipopolysaccharide (LPS), and hepatic cholesterol and triglyceride concentrations. OLA-treated obese mice exhibited higher fat preference compared to untreated obese mice, probably due to the increase in mRNA encoding CD36, a fat taste receptor, in mouse taste bud cells (mTBC). This phenomenon was associated with fatty-acid induced increases in free intracellular calcium concentrations, [Ca2+]i, induced in mTBC from OLA-treated obese mice. OLA also influenced the expression of mRNA encoding pro-inflammatory cytokines (IL-1β and IL-6) and some lipogenic genes (PPARα, SREBP1, FAS, ChREBP, and G6Pase) in liver and adipose tissue. These findings reveal that OLA improves gustatory perception of lipids and exerts protective effects in obesity.

Expression of the candidate fat taste receptors in human fungiform papillae and the association with fat taste function.

Significant experimental evidence supports fat as a taste modality; however, the associated peripheral mechanisms are not well established. Several candidate taste receptors have been identified, but their expression pattern and potential functions in human fungiform papillae remain unknown. The aim of this study is to identify the fat taste candidate receptors and ion channels that were expressed in human fungiform taste buds and their association with oral sensory of fatty acids. For the expression analysis, quantitative RT-PCR (qRT-PCR) from RNA extracted from human fungiform papillae samples was used to determine the expression of candidate fatty acid receptors and ion channels. Western blotting analysis was used to confirm the presence of the proteins in fungiform papillae. Immunohistochemistry analysis was used to localise the expressed receptors or ion channels in the taste buds of fungiform papillae. The correlation study was analysed between the expression level of the expressed fat taste receptors or ion channels indicated by qRT-PCR and fat taste threshold, liking of fatty food and fat intake. As a result, qRT-PCR and western blotting indicated that mRNA and protein of CD36, FFAR4, FFAR2, GPR84 and delayed rectifying K+ channels are expressed in human fungiform taste buds. The expression level of CD36 was associated with the liking difference score (R -0·567, β=-0·04, P=0·04) between high-fat and low-fat food and FFAR2 was associated with total fat intake (ρ=-0·535, β=-0·01, P=0·003) and saturated fat intake (ρ=-0·641, β=-0·02, P=0·008).

Oral lipase activities and fat-taste receptors for fat-taste sensing in chickens

It has been reported that a functional fat-taste receptor, GPR120, is present in chicken oral tissues, and that chickens can detect fat taste in a behavioral test. However, although triglycerides need to be digested to free fatty acids to be recognized by fat-taste receptors such as GPR120, it remains unknown whether lipase activities exist in chicken oral tissues. To examine this question, we first cloned another fat-taste receptor candidate gene, CD36, from the chicken palate. Then, using RT-PCR, we determined that GPR120 and CD36 were broadly expressed in chicken oral and gastrointestinal tissues. Also by RT-PCR, we confirmed that several lipase genes were expressed in both oral and gastrointestinal tissues. Finally, we analyzed the lipase activities of oral tissues by using a fluorogenic triglyceride analog as a lipase substrate. We found there are functional lipases in oral tissues as well as in the stomach and pancreas. These results suggested that chickens have a basic fat-taste reception system that incorporates a triglycerides/oral-lipases/free fatty acids/GPR120 axis and CD36 axis.

A review of the associations between single nucleotide polymorphisms in taste receptors, eating behaviors, and health

ABSTRACTFood preferences and dietary habits are heavily influenced by taste perception. There is growing interest in characterizing taste preferences based on genetic variation. Genetic differences in the ability to perceive key tastes may impact eating behavior and nutritional intake. Therefore, increased understanding of taste biology and genetics may lead to new personalized strategies, which may prevent or influence the trajectory of chronic disease risk. Recent advances show that single nucleotide polymorphisms (SNPs) in the CD36 fat taste receptor are linked to differences in fat perception, fat preference, and chronic-disease biomarkers. Genetic variation in the sweet taste receptor T1R2 has been shown to alter sweet taste preferences, eating behaviors, and risk of dental caries. Polymorphisms in the bitter taste receptor T2R38 have been shown to influence taste for brassica vegetables. Individuals that intensely taste the bitterness of brassica vegetables (“supertasters”) may avoid vegetable consumption and compensate by increasing their consumption of sweet and fatty foods, which may increase risk for chronic disease. Emerging evidence also suggests that the role of genetics in taste perception may be more impactful in children due to the lack of cultural influence compared to adults. This review examines the current knowledge of SNPs in taste receptors associated with fat, sweet, bitter, umami, and salt taste modalities and their contributions to food preferences, and chronic disease. Overall, these SNPs demonstrate the potential to influence food preferences and consequently health.

The role of G-protein-coupled receptor 120 in fatty acids sensing in chicken oral tissues

Clarification of the mechanism of chickens’ taste sense will provide meaningful information for creating and improving new feedstuff for chickens, because the character of taste receptors in oral tissues affects feeding behavior in animals. Although fatty acids are partly recognized via G-protein coupled receptor 120 (GPR120) for fat taste in mammalian oral tissues, the fat taste receptor of chickens has not been elucidated. Here we cloned chicken GPR120 (cGPR120) from the chicken palate, which contains taste buds. By using Ca2+ imaging methods, we identified oleic acid and linoleic acid as cGPR120 agonists. Interestingly, in a behavioral study the chickens preferred corn oil-rich feed over mineral oil (control oil)-rich feed. Because corn oil contains high amounts of oleic acid and linoleic acid, this result was thought to be reasonable. Taken together, the present results suggest that cGPR120 is one of the functional fat taste receptors in chickens.

CD36- and GPR120-Mediated Ca2+ Signaling in Human Taste Bud Cells Mediates Differential Responses to Fatty Acids and Is Altered in Obese Mice

It is important to increase our understanding of gustatory detection of dietary fat and its contribution to fat preference. We studied the roles of the fat taste receptors CD36 and GPR120 and their interactions via Ca(2+) signaling in fungiform taste bud cells (TBC). We measured Ca(2+) signaling in human TBC, transfected with small interfering RNAs against messenger RNAs encoding CD36 and GPR120 (or control small interfering RNAs). We also studied Ca(2+) signaling in TBC from CD36(-/-) mice and from wild-type lean and obese mice. Additional studies were conducted with mouse enteroendocrine cell line STC-1 that express GPR120 and stably transfected with human CD36. We measured release of serotonin and glucagon-like peptide-1 from human and mice TBC in response to CD36 and GPR120 activation. High concentrations of linoleic acid induced Ca(2+) signaling via CD36 and GPR120 in human and mice TBC, as well as in STC-1 cells, and low concentrations induced Ca(2+) signaling via only CD36. Incubation of human and mice fungiform TBC with lineoleic acid down-regulated CD36 and up-regulated GPR120 in membrane lipid rafts. Obese mice had decreased spontaneous preference for fat. Fungiform TBC from obese mice had reduced Ca(2+) and serotonin responses, but increased release of glucagon-like peptide-1, along with reduced levels of CD36 and increased levels of GPR120 in lipid rafts. CD36 and GPR120 have nonoverlapping roles in TBC signaling during orogustatory perception of dietary lipids; these are differentially regulated by obesity.

Assessment of the presence of chemosensing receptors based on bitter and fat taste in the gastrointestinal tract of young pig1

Knowledge on porcine bitter and fat taste receptors and on their expression in gastrointestinal tract of pigs is scarce. We searched for the presence of porcine homologous sequences for 13 human transcripts of bitter and fat taste receptors in ENSEMBL and National Center for Biotechnology Information databases. For taste 2 receptor (TAS2R) 8, alignment was not observed; for TAS2R13 and TAS2R46 the porcine predicted sequence aligned with several other human bitter genes. For 7 genes for bitter taste (TAS2R1, TAS2R3, TAS2R7, TAS2R9, TAS2R10, TAS2R16, and TAS2R38) and for 3 genes for fat taste (GPR40, GPR43, and GPR120), a full homology for exon sequences was found and primers were designed by Primer3. These 7 genes were amplified with real-time PCR and verified on agarose gel in 5 gastrointestinal segments of weaned pigs: oxyntic (ST1), pyloric (ST2), and cardiac to oxyntic transition mucosa (ST3), jejunum (JEJ), and colon (COL). Suitability of mRNA was verified by amplifying RPL4 and HMBS2 genes. Each bitter taste gene was detectable on agarose gel in at least 1 subject of all the gastrointestinal segments except for TAS2R3 and TAS2R38 that were never detected in ST1 and COL, respectively. The inspection of bitter taste genes amplification curve indicated that the expression was in general very low. GPR43 and GPR120 were present in all segments from all pigs. Expression was not detected for GPR40. Data also indicate that colon is the preeminent tract where fat detection by GPR120 takes place (P < 0.001). The presence of gene expression for several chemosensing receptors for bitter and fat taste in different compartments of the stomach confirms that this organ should be considered a player for the early detection of bolus composition.

G Protein-Coupled Receptors in Human Fat Taste Perception

In contrast to carbohydrates and proteins, which are detected by specialized taste receptors in the forms of their respective building blocks, sugars, and L-amino acids, the third macronutrient, lipids, has until now not been associated with gustatory receptors. Instead, the recognition of fat stimuli was believed to rely mostly on textural, olfactory, and postingestive cues. During the recent years, however, research done mainly in rodent models revealed an additional gustatory component for the detection of long-chain fatty acids (LCFAs), the main taste-activating component of lipids. Concomitantly, a number of candidate fat taste receptors were proposed to be involved in rodent's gustatory fatty acid perception. Compared with rodent models, much less is known about human fat taste. In order to investigate the ability of the human gustatory system to respond to fat components, we performed sensory experiments with fatty acids of different chain lengths and derivatives thereof. We found that our panelists discriminated a "fatty" and an irritant "scratchy" taste component, with the "fatty" percept restricted to LCFAs. Using functional calcium-imaging experiments with the human orthologs of mouse candidate fat receptors belonging to the G protein-coupled receptor family, we correlated human sensory data with receptor properties characterized in vitro. We demonstrated that the pharmacological activation profile of human GPR40 and GPR120, 2 LCFA-specific receptors associated with gustatory fat perception in rodents, is inconsistent with the "scratchy" sensation of human subjects and more consistent with the percept described as "fatty." Expression analysis of GPR40 and GPR120 in human gustatory tissues revealed that, while the GPR40 gene is not expressed, GPR120 is detected in gustatory and nongustatory epithelia. On a cellular level, we found GPR120 mRNA and protein in taste buds as well as in the surrounding epithelial cells. We conclude that GPR120 may indeed participate in human gustatory fatty acid perception.

Development of an in vitro system for screening the ligands of a membrane glycoprotein CD36.

It has well been known that human and rodents exhibit a preference for fats. This suggests the existence of an orosensory system responsible for the detection of dietary fats. A plasma membrane glycoprotein CD36, besides the role in the uptake of long-chain fatty acids (LCFAs) as well as oxidized low-density lipoprotein (OxLDL) in a variety of cells, has been postulated to be a candidate fat taste receptor on the tongue. Therefore, molecules that bind with CD36 to cause intracellular signaling but have fewer calories could be substitutes for dietary fats. In the present study, we developed an in vitro system for the screening of CD36 ligands using Chinese hamster ovary-K1 cells (CHO-K1) stably transfected with human or mouse CD36. When incubated with OxLDL labeled with fluorescence dye, the fluorescence was much higher in the transfected CHO-K1 cells than in non-transfected CHO-K1 cells. Incubation of the transfected cells with OxLDL caused a rapid phosphorylation of extracellular signal regulated kinase, and the degree was significantly higher compared with that in non-transfected CHO-K1 cells. The expression system using CHO-K1 cells could be a convenient tool to screen the novel ligands of CD36.