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Updated: Aug 20, 2025
Fat Preference: A Novel Model of Eating Behavior in Rats
Published on: June 27, 2014
Novel Fat Taste Receptor Agonists Curtail Progressive Weight Gain in Obese Male Mice
Amira Sayed Khan1, Aziz Hichami1, Babar Murtaza1
1NUTox, UMR UB/AgroSup/INSERM U1231, Lipides, Nutrition & Cancer, LABEX-LipStick, Université de Bourgogne-Franche Comté (UBFC), Dijon, 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.
Insights
Newly developed fat taste receptor agonists (FTA) activate tongue sensors, reducing food intake and weight gain in obese mice. This research suggests a novel strategy for obesity reduction by targeting oral fat perception.
Area of Science:
- * Physiology
- * Pharmacology
- * Obesity Research
Background:
- * Dietary lipid preference is regulated by CD36 and GPR120 fat taste receptors.
- * Malfunctioning of these receptors leads to reduced fat perception and obesity in humans and animals.
- * Targeting these receptors offers a potential strategy for managing obesity.
Purpose of the Study:
- * To synthesize and evaluate novel high-affinity fatty acid agonists (FTA) for CD36 and GPR120.
- * To investigate the effects of these agonists on fat taste perception and the tongue-gut axis.
- * To determine the efficacy of FTA in reducing food intake and obesity in a mouse model.
Main Methods:
- * Synthesis of two novel fat taste receptor agonists: NKS-3 (CD36 agonist) and NKS-5 (CD36 and GPR120 agonist).
- * Assessment of molecular interactions, Ca2+ signaling in mouse and human taste bud cells, and gustatory perception in mice.
- * Evaluation of the effects on the tongue-gut loop activation and obesity-related parameters in high-fat diet-fed mice.
Main Results:
- * NKS-3 and NKS-5 demonstrated enhanced Ca2+ signaling in taste bud cells compared to natural fatty acids.
- * Lingual application of FTA activated the tongue-gut loop, stimulating digestive secretions and hormone release.
- * Daily administration of NKS-3 or NKS-5 significantly reduced food intake and weight gain in obese mice.
Conclusions:
- * Novel chemical fat taste agonists can effectively target tongue fat sensors.
- * This approach shows promise as a new therapeutic strategy for reducing obesity.
- * Further research into oral fat perception modulation could lead to innovative anti-obesity treatments.
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