Novel Fat Taste Receptor Agonists Curtail Progressive Weight Gain in Obese Male Mice
Amira Sayed Khan, Aziz Hichami, Babar Murtaza, Marie‐Laure Louillat‐Habermeyer, Christophe Ramseyer, Maryam Azadi, Semen Yesylevskyy, Floriane Mangin, Frédéric Lirussi, Julia Leemput, Jean-François Merlin, Antonin Schmitt, Muhtadi Suliman, Jérôme Bayardon, Saeed Semnanian, Sylvain Jugé, Naim Akhtar Khan
Abstract
BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Our results show that targeting fat sensors in the tongue by novel chemical fat taste agonists might represent a new strategy to reduce obesity.