Novel Fat Taste Receptor Agonists Curtail Progressive Weight Gain in Obese Male MiceSummary
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 w...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Cellular and Molecular Gastroenterology and Hepatology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352345X22002363 |
| _version_ | 1797903559753203712 |
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| author | Amira Sayed Khan Aziz Hichami Babar Murtaza Marie-Laure Louillat-Habermeyer Christophe Ramseyer Maryam Azadi Semen Yesylevskyy Floriane Mangin Frederic Lirussi Julia Leemput Jean-Francois Merlin Antonin Schmitt Muhtadi Suliman Jérôme Bayardon Saeed Semnanian Sylvain Jugé Naim Akhtar Khan |
| author_facet | Amira Sayed Khan Aziz Hichami Babar Murtaza Marie-Laure Louillat-Habermeyer Christophe Ramseyer Maryam Azadi Semen Yesylevskyy Floriane Mangin Frederic Lirussi Julia Leemput Jean-Francois Merlin Antonin Schmitt Muhtadi Suliman Jérôme Bayardon Saeed Semnanian Sylvain Jugé Naim Akhtar Khan |
| author_sort | Amira Sayed Khan |
| collection | DOAJ |
| description | 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: We synthesized 2 fat taste receptor agonists (FTA), NKS-3 (CD36 agonist) and NKS-5 (CD36 and GPR120 agonist). We determined their molecular dynamic interactions with fat taste receptors and the effect on Ca2+ 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: The two FTA, NKS-3 and NKS-5, triggered higher Ca2+ 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. |
| first_indexed | 2024-04-10T09:34:53Z |
| format | Article |
| id | doaj.art-faac987bf7904e528f779ff44b123109 |
| institution | Directory Open Access Journal |
| issn | 2352-345X |
| language | English |
| last_indexed | 2024-04-10T09:34:53Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cellular and Molecular Gastroenterology and Hepatology |
| spelling | doaj.art-faac987bf7904e528f779ff44b1231092023-02-18T04:17:04ZengElsevierCellular and Molecular Gastroenterology and Hepatology2352-345X2023-01-01153633663Novel Fat Taste Receptor Agonists Curtail Progressive Weight Gain in Obese Male MiceSummaryAmira Sayed Khan0Aziz Hichami1Babar Murtaza2Marie-Laure Louillat-Habermeyer3Christophe Ramseyer4Maryam Azadi5Semen Yesylevskyy6Floriane Mangin7Frederic Lirussi8Julia Leemput9Jean-Francois Merlin10Antonin Schmitt11Muhtadi Suliman12Jérôme Bayardon13Saeed Semnanian14Sylvain Jugé15Naim Akhtar Khan16NUTox, UMR UB/AgroSup/INSERM U1231, Lipides, Nutrition & Cancer, LABEX-LipStick, Université de Bourgogne-Franche Comté (UBFC), Dijon, FranceNUTox, UMR UB/AgroSup/INSERM U1231, Lipides, Nutrition & Cancer, LABEX-LipStick, Université de Bourgogne-Franche Comté (UBFC), Dijon, FranceNUTox, UMR UB/AgroSup/INSERM U1231, Lipides, Nutrition & Cancer, LABEX-LipStick, Université de Bourgogne-Franche Comté (UBFC), Dijon, FranceICMUB-OCS, UMR CNRS 6302, Université de Bourgogne-Franche Comté (UBFC), Dijon, FranceLaboratoire ChronoEnvironnement, UMR CNRS6249, Université de Bourgogne Franche-Comté (UBFC), Besançon, FranceDepartment of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, IranLaboratoire ChronoEnvironnement, UMR CNRS6249, Université de Bourgogne Franche-Comté (UBFC), Besançon, France; Department of Physics of Biological Systems, Institute of Physics of the National Academy of Sciences of Ukraine, Kyiv, UkraineICMUB-OCS, UMR CNRS 6302, Université de Bourgogne-Franche Comté (UBFC), Dijon, FranceHSP-pathies, UMR UB/AgroSup/INSERM U1231, Lipides, Nutrition & Cancer, Université de Bourgogne-Franche Comté (UBFC), Dijon, FranceNUTox, UMR UB/AgroSup/INSERM U1231, Lipides, Nutrition & Cancer, LABEX-LipStick, Université de Bourgogne-Franche Comté (UBFC), Dijon, FranceNUTox, UMR UB/AgroSup/INSERM U1231, Lipides, Nutrition & Cancer, LABEX-LipStick, Université de Bourgogne-Franche Comté (UBFC), Dijon, FranceHSP-pathies, UMR UB/AgroSup/INSERM U1231, Lipides, Nutrition & Cancer, Université de Bourgogne-Franche Comté (UBFC), Dijon, FranceNUTox, UMR UB/AgroSup/INSERM U1231, Lipides, Nutrition & Cancer, LABEX-LipStick, Université de Bourgogne-Franche Comté (UBFC), Dijon, FranceICMUB-OCS, UMR CNRS 6302, Université de Bourgogne-Franche Comté (UBFC), Dijon, FranceDepartment of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, IranICMUB-OCS, UMR CNRS 6302, Université de Bourgogne-Franche Comté (UBFC), Dijon, FranceNUTox, UMR UB/AgroSup/INSERM U1231, Lipides, Nutrition & Cancer, LABEX-LipStick, Université de Bourgogne-Franche Comté (UBFC), Dijon, France; Correspondence Address correspondence to: Naim Khan, PhD, DSc, U1231 INSERM, Physiologie de la Nutrition & Toxicologie (NUTox), Université de Bourgogne-Franche Comté (UBFC), Dijon 21000, France.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: We synthesized 2 fat taste receptor agonists (FTA), NKS-3 (CD36 agonist) and NKS-5 (CD36 and GPR120 agonist). We determined their molecular dynamic interactions with fat taste receptors and the effect on Ca2+ 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: The two FTA, NKS-3 and NKS-5, triggered higher Ca2+ 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.http://www.sciencedirect.com/science/article/pii/S2352345X22002363Fat TasteLipidsCD36GPR120Obesity |
| spellingShingle | Amira Sayed Khan Aziz Hichami Babar Murtaza Marie-Laure Louillat-Habermeyer Christophe Ramseyer Maryam Azadi Semen Yesylevskyy Floriane Mangin Frederic Lirussi Julia Leemput Jean-Francois Merlin Antonin Schmitt Muhtadi Suliman Jérôme Bayardon Saeed Semnanian Sylvain Jugé Naim Akhtar Khan Novel Fat Taste Receptor Agonists Curtail Progressive Weight Gain in Obese Male MiceSummary Cellular and Molecular Gastroenterology and Hepatology Fat Taste Lipids CD36 GPR120 Obesity |
| title | Novel Fat Taste Receptor Agonists Curtail Progressive Weight Gain in Obese Male MiceSummary |
| title_full | Novel Fat Taste Receptor Agonists Curtail Progressive Weight Gain in Obese Male MiceSummary |
| title_fullStr | Novel Fat Taste Receptor Agonists Curtail Progressive Weight Gain in Obese Male MiceSummary |
| title_full_unstemmed | Novel Fat Taste Receptor Agonists Curtail Progressive Weight Gain in Obese Male MiceSummary |
| title_short | Novel Fat Taste Receptor Agonists Curtail Progressive Weight Gain in Obese Male MiceSummary |
| title_sort | novel fat taste receptor agonists curtail progressive weight gain in obese male micesummary |
| topic | Fat Taste Lipids CD36 GPR120 Obesity |
| url | http://www.sciencedirect.com/science/article/pii/S2352345X22002363 |
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