FAHFA promotes intracellular calcium signaling via activating the fat taste receptor, CD36 and Src protein kinases in mice taste bud cells

• Published in: Biochimica et biophysica acta. General subjects Vol. 1868; no. 12; p. 130722
• Main Authors: Muthuswamy, Karthi, Vasanthakumar, Keerthana, Panneerselvan, Prabha, Thangamani, Lokesh, Krishnan, Vasanth, Piramanayagam, Shanmughavel, Subramaniam, Selvakumar
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.12.2024
• Subjects: Animals; Calcium - metabolism; Calcium Signaling; CD36; CD36 Antigens - metabolism; FAHFAs; Fat; GPR120; Male; Mice; Mice, Inbred C57BL; Receptors, G-Protein-Coupled - metabolism; src-Family Kinases - metabolism; Taste - physiology; Taste Buds - metabolism; Fat; FAHFAs; GPR120; CD36
• ISSN: 0304-4165; 1872-8006; 1872-8006
• DOI: 10.1016/j.bbagen.2024.130722

Two lipid sensors, CD36 and GPR120, are crucial for the orosensory detection of fat taste and for mediating fat preference. However, the mechanism by which endogenous lipid (FAHFA) binds to CD36 to initiate intracellular signaling remains unexplained. Hence, the primary objective of this study is to investigate the binding mechanism of FAHFA to CD36 and its role in isolated mouse taste bud cells (mTBCs). The Schrodinger platform was used to assess the molecular dynamics of protein and ligand interactions, and an in vitro experiment was used to validate the findings. Based on the docking score of the ligand, the molecular mechanistic activities of the targeted complexes, CD36–5-POHSA (−8.2 kcal/mol), were investigated using the dynamic simulation. In comparison to linoleic acid (LA), POHSA rapidly increased [Ca2+]i via acting on CD36, and 5-POHSA treatment in mTBCs activated src-kinase at 20 μM. CD36 siRNA transfection in TBCs downregulate the CD36 protein expression as well as [Ca2+]i flux. This study suggests that 5-POHSA may help combat taste abnormalities and the adverse effects of obesity by binding to the lingual CD36 receptor and activating the tongue-brain axis. •Targeting fat taste offers a potential therapeutic avenue for reducing body weight and fat consumption.•Studies on mouse fungiform taste bud cells reveal dose-dependent calcium responses to fat taste agonists, highlighting the role of CD36 activation.•Src family kinases play a crucial role in fat-tasting impacts, potentially through CD36 activation.