The role of lipolysis in human orosensory fat perception.

Taste perception elicited by food constituents and facilitated by sensory cells in the oral cavity is important for the survival of organisms. In addition to the five basic taste modalities, sweet, umami, bitter, sour, and salty, orosensory perception of stimuli such as fat constituents is intensely investigated. Experiments in rodents and humans suggest that free fatty acids represent a major stimulus for the perception of fat-containing food. However, the lipid fraction of foods mainly consists of triglycerides in which fatty acids are esterified with glycerol. Whereas effective lipolysis by secreted lipases (LIPs) liberating fatty acids from triglycerides in the rodent oral cavity is well established, a similar mechanism in humans is disputed. By psychophysical analyses of humans, we demonstrate responses upon stimulation with triglycerides which are attenuated by concomitant LIP inhibitor administration. Moreover, lipolytic activities detected in minor salivary gland secretions directly supplying gustatory papillae were correlated to individual sensitivities for triglycerides, suggesting that differential LIP levels may contribute to variant fat perception. Intriguingly, we found that the LIPF gene coding for lingual/gastric LIP is not expressed in human lingual tissue. Instead, we identified the expression of other LIPs, which may compensate for the absence of LIPF.

Taste preferences.

Personal experience, learned eating behaviors, hormones, neurotransmitters, and genetic variations affect food consumption. The decision of what to eat is modulated by taste, olfaction, and oral textural perception. Taste, in particular, has an important input into food preference, permitting individuals to differentiate nutritive and harmful substances and to select nutrients. To be perceived as taste, gustatory stimuli have to contact specialized receptors and channels expressed in taste buds in the oral cavity. Gustatory information is then conveyed via afferent nerves to the central nervous system, which processes the gustatory information at different levels, resulting in stimulus recognition, integration with metabolic needs, and control of ingestive reflexes. This review discusses physiological factors influencing the decision of what to eat, spanning the bow from the recognition of the nutritive value of food in the oral cavity, over the feedback received after ingestion, to processing of gustatory information to the central nervous system.

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.

Characterization of Trypanosoma cruzi telomerase.

High telomerase activity is always associated with actively dividing cells, however the detection of this activity in dividing Leishmania and Trypanosoma cruzi cells has always been disappointingly low. Recently, we have found that Leishmania major telomerase activity can be activated by heat, which combined with dilutions of the nuclear extracts produced an increase in activity comparable to cancer cells. Here we examined whether T. cruzi telomerase shares the same physicochemical properties of primer specificity and overall features of the L. major. Our studies revealed that no telomerase inhibitory factors were present in the nuclear lysates of T. cruzi however the enzyme was activated by heat and was very resilient to heat denaturation. We also showed the extension primer specificity, susceptibility to RNase-A and RNase-H digestion, and the effect of telomerase inhibitors.

Modulation of bitter taste perception by a small molecule hTAS2R antagonist.

Human bitter taste is mediated by the hTAS2R family of G protein-coupled receptors. The discovery of the hTAS2Rs enables the potential to develop specific bitter receptor antagonists that could be beneficial as chemical probes to examine the role of bitter receptor function in gustatory and nongustatory tissues. In addition, they could have widespread utility in food and beverages fortified with vitamins, antioxidants, and other nutraceuticals, because many of these have unwanted bitter aftertastes. We employed a high-throughput screening approach to discover a novel bitter receptor antagonist (GIV3727) that inhibits activation of hTAS2R31 (formerly hTAS2R44) by saccharin and acesulfame K, two common artificial sweeteners. Pharmacological analyses revealed that GIV3727 likely acts as an orthosteric, insurmountable antagonist of hTAS2R31. Surprisingly, we also found that this compound could inhibit five additional hTAS2Rs, including the closely related receptor hTAS2R43. Molecular modeling and site-directed mutagenesis studies suggest that two residues in helix 7 are important for antagonist activity in hTAS2R31 and hTAS2R43. In human sensory trials, GIV3727 significantly reduced the bitterness associated with the two sulfonamide sweeteners, indicating that hTAS2R antagonists are active in vivo. Our results demonstrate that small molecule bitter receptor antagonists can effectively reduce the bitter taste qualities of foods, beverages, and pharmaceuticals.

A heat-activated and thermoresistant telomerase activity in Leishmania major Friedlin.

Here we studied the telomerase activity of the human parasite Leishmania major. In this organism we have detected a high activity of this enzyme once several parameters such as heat activation, sequence of extension primer, and protein concentration are adjusted. The activity was not only heat activated, but also very resistant to heat denaturation. We believe L. major telomerase is an important activity and it may provide an adequate drug therapy target.