The sense of taste informs the body about the quality of ingested foods. Tastant‐mediated signals are generated by a rise in free intracellular calcium levels ([Ca ²⁺ ]i) in the taste bud cells and then are transferred to the gustatory area of brain via connections between the gustatory nerves (chorda tym‐ pani and glossopharyngeal nerves) and the nucleus of solitary tract in the brain stem. We have recently shown that lingual CD36 contributes to fat preference and early digestive secretions in the mouse. We show here that 1 ) the induction of an increase in [Ca ²⁺ ]i by linoleic acid is CD36‐dependent in taste receptor cells, 2) the spontaneous preference for or conversely con ditioned aversion to linoleic acid requires intact gusta tory nerves, and 3) the activation of gustatory neurons in the nucleus of the solitary tract elicited by a linoleic acid deposition on the tongue in wild‐type mice cannot be reproduced in CD36‐null animals. We conclude that the CD36‐mediated perception of long‐chain fatty acids involves the gustatory pathway, suggesting that the mouse may have a “taste“ for fatty foods. This system would constitute a potential physiological advantage under conditions of food scarcity by leading the mouse to select and absorb fatty foods. However, it might also lead to a risk of obesity and associated diseases in a context of constantly abundant food.—Gaillard, D., Laugerette, F., Darcel, N., El‐Yassimi, A., Passilly‐De grace, P., Hichami, A., Khan, N. A., Montmayeur, J.‐P., Besnard, P. The gustatory pathway is involved in CD36‐ mediated orosensory perception of long‐chain fatty acids in the mouse. FASEB J . 22, 1458–1468 (2008)

Recent studies in rodents and humans suggest that the chemoreception of long-chain fatty acids (LCFA) in oral cavity is involved in the spontaneous preference for fatty foods and might contribute to the obesity risk. CD36 and GPR120 are LCFA receptors identified in rodent taste bud cells. The fact that CD36 or GPR120 gene inactivation leads to a decrease in the preference for lipids raises the question of the respective role(s) played by these gustatory lipid-sensor candidates. Using a combination of biochemical, nutritional and behavioural studies in wild-type, CD36^+/−and CD36^−/− mice, it was found that: 1°) CD36 and GPR120 display different diurnal rhythms in the gustatory circumvallate papillae, CD36 mRNA levels being down-regulated during the dark period in contrast to GPR120, 2°) this change is due to food intake and strictly dependent of the presence of lipids in the diet, 3°) CD36 protein levels are also rapidly but transiently decreased by the food intake, a two-fold drop in CD36 protein levels being found 1 h after refeeding, followed by a progressive return to the pre-prandial values, 4°) this down-regulation, which has a post-transcriptional origin, seems sufficient to alter the spontaneous fat preference, independently to change in the GPR120 gene expression. In contrast to GPR120, CD36 appears to be a food-sensitive lipid sensor in the gustatory circumvallate papillae. Lipid-mediated change in lingual CD36 expression might modulate the motivation for fat during a meal, initially high and then gradually decreasing secondary to the food intake. This short-term lipid-mediated effect is reminiscent of sensory-specific satiety. These findings, which highlight the role played by CD36 in the oro-sensory perception of dietary lipids, raise the possibility of novel pharmacological strategies to modify attraction for fatty foods and decrease obesity risks.

HumanWNT10Amutations are associated with developmental tooth abnormalities and adolescent onset of a broad range of ectodermal defects. Here we show that β-catenin pathway activity and adult epithelial progenitor proliferation are reduced in the absence of WNT10A, and identify Wnt-active self-renewing stem cells in affected tissues including hair follicles, sebaceous glands, taste buds, nails and sweat ducts. Human and mouseWNT10Amutant palmoplantar and tongue epithelia also display specific differentiation defects that are mimicked by loss of the transcription factor KLF4. We find that β-catenin interacts directly with region-specific LEF/TCF factors, and with KLF4 in differentiating, but not proliferating, cells to promote expression of specialized keratins required for normal tissue structure and integrity. Our data identify WNT10A as a critical ligand controlling adult epithelial proliferation and region-specific differentiation, and suggest downstream β-catenin pathway activation as a potential approach to ameliorate regenerative defects inWNT10Apatients.

Continuous taste bud cell renewal is essential to maintain taste function in adults; however, the molecular mechanisms that regulate taste cell turnover are unknown. Using inducible Cre-lox technology, we show that activation of β-catenin signaling in multipotent lingual epithelial progenitors outside of taste buds diverts daughter cells from a general epithelial to a taste bud fate. Moreover, while taste buds comprise 3 morphological types, β-catenin activation drives overproduction of primarily glial-like Type I taste cells in both anterior fungiform (FF) and posterior circumvallate (CV) taste buds, with a small increase in Type II receptor cells for sweet, bitter and umami, but does not alter Type III sour detector cells. Beta-catenin activation in post-mitotic taste bud precursors likewise regulates cell differentiation; forced activation of β-catenin in these Shh⁺ cells promotes Type I cell fate in both FF and CV taste buds, but likely does so non-cell autonomously. Our data are consistent with a model where β-catenin signaling levels within lingual epithelial progenitors dictate cell fate prior to or during entry of new cells into taste buds; high signaling induces Type I cells, intermediate levels drive Type II cell differentiation, while low levels may drive differentiation of Type III cells. Taste is a fundamental sense that helps the body determine whether food can be ingested. Taste dysfunction can be a side effect of cancer therapies, can result from an alteration of the renewal capacities of the taste buds, and is often associated with psychological distress and malnutrition. Thus, understanding how taste cells renew throughout adult life, i.e. how newly born cells replace old cells as they die, is essential to find potential therapeutic targets to improve taste sensitivity in patients suffering taste dysfunction. Here we show that a specific molecular pathway, Wnt/β-catenin signaling, controls renewal of taste cells by regulating separate stages of taste cell turnover. We show that activating this pathway directs the newly born cells to become primarily a specific taste cell type whose role is to support the other taste cells and help them work efficiently.

The natural like and dislike of foods based on taste is one of the most easily observed behaviors in animals. Animals eat palatable foods and reject aversive foods, which makes measurement of taste perception possible using various behavioral techniques. Three different methods to accurately measure taste behavior are described here. First, two‐bottle preference tests evaluate whether a taste compound (tastant) is preferred over water. Second, lickometer tests quantify the like and dislike for multiple concentrations of the same tastant or multiple tastants at the same time. Finally, conditioned taste aversion tests accurately determine the perceived taste threshold for palatable tastants. Together, these diverse methods enable researchers to observe and measure behavioral taste responses in mice to any tastant. © 2016 by John Wiley & Sons, Inc.