Implication of TRPC3 channel in gustatory perception of dietary lipids.

AIM: The pathogenesis of obesity has been associated with high intake of dietary fat, and some recent studies have explored the cellular mechanisms of oro-sensory detection of dietary fatty acids. We further assessed the role of transient receptor potential canonical (TRPC) channels in oro-sensory perception of dietary lipids. METHODS: We determined by RT-qPCR and western blotting the expression of TRPC3/6/7 channels in mouse fungiform taste bud cells (mTBC). Immunocytochemistry was used to explore whether TRPC3 channels were co-expressed with fatty acid receptors. We employed wild-type (WT) mTBC, and those transfected with small interfering RNAs (siRNAs) against TRPC3 or STIM1. Ca2+ signalling was studied in TBC from TRPC3-/- mice and their WT littermates. RESULTS: We demonstrate that mouse fungiform taste bud cells (mTBC) express TRPC3, but not TRPC6 or TRPC7 channels, and their inactivation by siRNA or experiments on TBC from TRPC3-/- mice brought about a decrease in fatty acid-induced gustatory Ca2+ signalling, coupled with taste bud CD36 lipid sensor. TRPC3 channel activation was found to be under the control of STIM1 in lingual mTBC. Behavioural studies showed that spontaneous preference for a dietary long-chain fatty acid was abolished in TRPC3-/- mice, and in mice wherein lingual TRPC3 expression was silenced by employing siRNA. CONCLUSION: We report that lingual TRPC3 channels are critically involved in fat taste perception.

Preference for dietary fat: From detection to disease.

Recent advances in the field of taste physiology have clarified the role of different basic taste modalities and their implications in health and disease and proposed emphatically that there might be a distinct cue for oro-sensory detection of dietary long-chain fatty acids (LCFAs). Hence, fat taste can be categorized as a taste modality. During mastication, LCFAs activate tongue lipid sensors like CD36 and GPR120 triggering identical signaling pathways as the basic taste qualities do; however, the physico-chemical perception of fat is not as distinct as sweet or bitter or other taste sensations. The question arises whether "fat taste" is a basic or "alimentary" taste. There is compelling evidence that fat-rich dietary intervention modulates fat taste perception where an increase or a decrease in lipid contents in the diet results, respectively, in downregulation or upregulation of fat taste sensitivity. Evidently, a decrease in oro-sensory detection of LCFAs leads to high fat intake and, consequently, to obesity. In this article, we discuss recent relevant advances made in the field of fat taste physiology with regard to dietary fat preference and lipid sensors that can be the target of anti-obesity strategies.

Novel GPR120 agonist TUG891 modulates fat taste perception and preference and activates tongue-brain-gut axis in mice.

GPR120 is implicated as a lipid receptor in the oro-sensory detection of dietary fatty acids. However, the effects of GPR120 activation on dietary fat intake or obesity are not clearly understood. We investigated to determine whether the binding of TUG891, a novel GPR120 agonist, to lingual GPR120 modulates fat preference in mice. We explored the effects of TUG891 on obesity-related hormones and conducted behavioral choice tests on mice to better understand the physiologic relevance of the action of TUG891. In cultured mouse and human taste bud cells (TBCs), TUG891 induced a rapid increase in Ca2+ by acting on GPR120. A long-chain dietary fatty acid, linoleic acid (LA), also recruited Ca2+ via GPR120 in human and mouse TBCs. Both TUG891 and LA induced ERK1/2 phosphorylation and enhanced in vitro release of glucagon-like peptide-1 from cultured human and mouse TBCs. In situ application of TUG891 onto the tongue of anesthetized mice triggered the secretion of pancreatobiliary juice, probably via the tongue-brain-gut axis. Furthermore, lingual application of TUG891 altered circulating concentrations of cholecystokinin and adipokines, associated with decreased circulating LDL, in conscious mice. In behavioral tests, mice exhibited a spontaneous preference for solutions containing either TUG891 or LA instead of a control. However, addition of TUG891 to a solution containing LA significantly curtailed fatty acid preference. Our study demonstrates that TUG891 binds to lingual GPR120 receptors, activates the tongue-brain-gut axis, and modulates fat preference. These findings may support the development of new fat taste analogs that can change the approach to obesity prevention and treatment.

Octadecaneuropeptide (ODN) Induces N2a Cells Differentiation through a PKA/PLC/PKC/MEK/ERK-Dependent Pathway: Incidence on Peroxisome, Mitochondria, and Lipid Profiles.

Neurodegenerative diseases are characterized by oxidative stress, mitochondrial damage, and death of neuronal cells. To counteract such damage and to favor neurogenesis, neurotrophic factors could be used as therapeutic agents. Octadecaneuropeptide (ODN), produced by astrocytes, is a potent neuroprotective agent. In N2a cells, we studied the ability of ODN to promote neuronal differentiation. This parameter was evaluated by phase contrast microscopy, staining with crystal violet, cresyl blue, and Sulforhodamine 101. The effect of ODN on cell viability and mitochondrial activity was determined with fluorescein diacetate and DiOC6(3), respectively. The impact of ODN on the topography of mitochondria and peroxisomes, two tightly connected organelles involved in nerve cell functions and lipid metabolism, was evaluated by transmission electron microscopy and fluorescence microscopy: detection of mitochondria with MitoTracker Red, and peroxisome with an antibody directed against the ABCD3 peroxisomal transporter. The profiles in fatty acids, cholesterol, and cholesterol precursors were determined by gas chromatography, in some cases coupled with mass spectrometry. Treatment of N2a cells with ODN (10-14 M, 48 h) induces neurite outgrowth. ODN-induced neuronal differentiation was associated with modification of topographical distribution of mitochondria and peroxisomes throughout the neurites and did not affect cell viability and mitochondrial activity. The inhibition of ODN-induced N2a differentiation with H89, U73122, chelerythrine and U0126 supports the activation of a PKA/PLC/PKC/MEK/ERK-dependent signaling pathway. Although there is no difference in fatty acid profile between control and ODN-treated cells, the level of cholesterol and some of its precursors (lanosterol, desmosterol, lathosterol) was increased in ODN-treated cells. The ability of ODN to induce neuronal differentiation without cytotoxicity reinforces the interest for this neuropeptide with neurotrophic properties to overcome nerve cell damage in major neurodegenerative diseases.

A cross-talk between fat and bitter taste modalities.

The choice of food is governed largely by the sense of taste. To date, five basic taste modalities have been described; however, there is an increasing agreement on the existence of a 6th fat taste. The taste modalities might interact with each other and also with other senses. The advancements in cellular and molecular biology have helped the characterization of taste signaling mechanisms, down to the receptor level and beyond. CD36 and GPR120 have been shown to be involved in the detection of fat taste while bitter taste is perceived by a number of receptors that belong to a family of taste-type 2 receptors (T2R or TAS2R). Hence, the most common role is played by TAS2R16 and TAS2R38 in bitter taste perception in humans. Increasing evidences from behavioural studies suggest that fat and bitter taste modalities might interact with each other, and this interaction might be critical in obesity. In the current review, we will discuss the evidence from genetic and behavioural studies and propose the molecular mechanism of a cross-talk between fat and bitter tastes.

The rs1527483, but not rs3212018, CD36 polymorphism associates with linoleic acid detection and obesity in Czech young adults.

Recent evidence has raised the possibility of the existence of a sixth taste modality - that is, taste for fat - which is mediated by lingual CD36 and plays a role in obesity. Consequently, the genetic polymorphism of CD36 has been shown to be associated with altered oro-sensory detection of dietary lipids. In the present study, we investigated the relationship between oro-sensory perception of linoleic acid (LA), two CD36 polymorphisms (rs1527483 and rs3212018), obesity parameters and craving habits for dietary lipids in young Czech adults. We also sequenced 5 and 6 exons of CD36 to trace out any new mutation that might be responsible for the difference in taste perception. We observed that craving for dietary lipids was correlated with anthropometric parameters (P<0·05) and LA detection threshold (P=0·033). The participants with the CC genotype of the rs1527483 polymorphism had lower BMI (P=0·011), waist circumference (P=0·005), waist:height ratio (P=0·010) and higher sensitivity for LA (P=0·037) than the participants with the CT and TT genotypes. Interestingly, we did not observe any association between the rs3212018 polymorphism and the studied parameters. Moreover, we did not observe any mutation in exons 5 and 6 of the CD36 gene in these subjects. Finally, we can state that rs1527483, but not rs3212018, is associated with high body weight in young Czech subjects.

Alteration in Taste Perception in Cancer: Causes and Strategies of Treatment.

The sense of taste is responsible for the detection and ingestion of food to cover energetic requirements in health and disease. The change in taste perception might lead to malnutrition that is usually one of the frequent causes of morbidity and mortality in patients with cancer. In this review, we summarize the mechanisms of taste perception and how they are altered in cancer. We also address the question of the implication of inflammation, responsible for the alterations in taste modalities. We highlight the role of radio- and chemotherapy in the modulation of taste physiology. Other several factors like damage to taste progenitor cells and disruption of gut microbiota are also dealt with relation to taste perception in cancer. We further shed light on how to restore taste acuity, by using different preventive methods, dietary modifications and pharmacotherapy in subjects with advanced cancer state.