Functional characterization of Gpr120 expressing cells and their role in fatty acid detection in knock-in mouse models
Molecular Biology and Physiology of Neurons and Glial Cells
Final Report Abstract
The gustatory system allows the detection of many food compounds and their discrimination into five well-known taste sensations (i.e. bitter, sweet, salty, sour, and umami). With the rampant obesity epidemic affecting western countries and the over-consumption of calorie-rich food, research aiming to elucidate the factors involved in consumption and metabolism of calorie-rich food (sugar and fat) is important. The discovery of a detector of free fatty acids on the tongue in rodents as well as sensors of sweet compounds in the gut opens new avenues and suggests that these sensors placed at strategic locations along the digestive system play an important role during the transit and metabolism of these compounds in the body. This assumption is confirmed in animals lacking these detectors as they also lose their attraction to fatty acids or sugar. Using molecular biology techniques we have isolated a new detector of long-chain fatty acids (i.e. GPR120) from the taste buds of the circumvallate papillae. Taste buds are groups of cells specialized in chemical detection which cover the surface of the tongue. The importance of this detector in linoleic acid preference was demonstrated by colleagues studying mice without this detector. In order to establish the exact distribution of this new sensor throughout the body and make primary GPR120-expressing cells amenable for electrophysiological and pharmacological analyses, we have generated a novel mouse strain in which the cells containing this detector are fluorescent. In addition, we also generated two other mouse strains, which can be used to eliminate GPR120 from taste cells without affecting its presence in other tissues (adipocytes, immune cells, etc.). With these new genetic tools, which allow visualization and tissue specific ablation of GPR120 we will now analyze the contribution of oral GPR120 in food choices. Systematic analysis of the location of GPR120 at the level of the whole organism in the novel knock-in mouse strain confirms that it is abundant in adipose tissue and immune cells where it plays a role in inflammation. Moreover, we provide for the first time genetic confirmation of GPR120 expression in taste receptor cells of the taste buds. Furthermore, these tools will allow us to refine the contribution of GPR120 in dietary fat preference in mice. Given the role of GPR120 in inflammation, obesity and fat preference it is highly probable that pharmacological compounds modulating the activity of this receptor for medical purposes or to reduce calories in the food industry will be identified. Knowledge of the organs and tissues that these potential new drugs will be targeting is very valuable when it comes to the safety of such compounds and their long term effects on wellness and health.
Publications
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Workshop on Taste and Food Acceptance, Procida, Italy, April 14-18 (2010). GPR120, a G-protein-coupled receptors expressed in mouse taste papillae
Montmayeur J-P., Fenech C., Kusumakshi S., Laugerette F., Liu Z., Wiencis A., Boehm U.
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European Chemoreception Research Organization (ECRO) XXth congress, September 14-19 (2010), Avignon, France. A screening for G-protein-coupled receptors expressed in mouse taste papillae. Chem. Senses 36(1): E43 (2011)
Montmayeur J-P., Fenech C., Kusumakshi S., Laugerette F., Liu Z., Wiencis A., Boehm U.
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Screening for G-protein-coupled receptors expressed in mouse taste papillae. Flavour Frag. J. (2011) 26:223-230
Montmayeur J-P., Fenech C., Kusumakshi S., Laugerette F., Liu Z., Wiencis A., Boehm U.
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European Chemoreception Research Organization (ECRO), August 26-29 (2013), Leuven, Belgium.A binary genetic strategy to visualize and manipulate TRPM5-expressing cells in mice. P047
Kusumakshi S., Voigt A., Hubner S., Dörr J., Meyerhof W., Flockerzi V., Montmayeur J-P., Boehm U.
