Table 3.

Proteins involved in fat chemosensation

Protein	Study (Reference), Year	Findings
α-Gustducin	Avau et al. (86), 2015	α-Gustducin is involved in fat intake and obesity.
	Watanabe et al. (80), 2019	ADRB3 is an essential mediator of fat perception and metabolism in the body. The Trp64Arg variant of this gene is associated with high-fat preference, indicating the structure of the adrenergic receptor protein may play a role in oral fat perception.
ADRB3	Sclafani et al. (124), 2018	CALHM1 KO mice displayed even greater intralipid preference deficits compared with WT and CD36 KO mice. Suggesting that non-CD36 taste receptors also contribute to fat detection and preference. CALHM1 KOs can still develop normal preferences after multiple exposures (not in naïve) attributed to post-oral fat conditionin
CALHM1	Subramaniam et al. (126), 2016	CALHM1 channels are upstream regulators of LA-induced ERK1/2 phosphorylation. LA-induced Ca2+ signaling and ERK1/2 phosphorylation are impaired in Calhm1-/- TBCs. Preference for fat is abolished in Calhm1-/- mice.
	Braymer et al. (89), 2017	CD36 mRNA levels were increased in lean rats.
		Lingual application of CD36 siRNA decreased fat preference in lean, obesity-resistant rats.
CB1R	Avalos et al. (85), 2020	CB1R knockout (KO) mice displayed an attenuated preference for HFD for the first 6 hours of a preference test compared to WT mice.
CD36	Bricio-Barrios et al. (52), 2019	BMI was associated with low serum CD36 and lower fat sensitivity.
	Djeziri et al. (96), 2018	CD36 inhibition prevented lipid-induced intracellular calcium increases. CD36 expression was decreased with HFD alone but increased with oleic acid.
	Gaudet et al. (99), 2019	Continuous access to HFD increased lingual CD36 expression in rats.
	Lee et al. (107), 2015	CD36 contributes to lipid recognition in mice.
	Lee et al. (108), 2017	Wild-type, but not CD36-knockout mice, were able to detect oleic aldehyde, providing evidence for the involvement in CD36 in in the perception of dour-active volatile compounds in the nasal cavity.
	Ozdener et al. (115), 2014	High concentrations of linoleic acid induced Ca2+ signaling via CD36 and GPR120 in human and mice TBC, as well as in STC-1 cells, and low concentrations induced Ca2+ signaling via only CD36. CD36 and GPR120 have nonoverlapping roles in TBC signaling during orogustatory perception of dietary lipids; these are differentially regulated by obesity.
	Sclafani et al. (124), 2018	CD36 KO reduced preference for lipids (in naïve CD36 KO).
	Subramaniam et al. (126), 2016	CD36 is involved in FA induction of ERK1/2 phosphorylation. LA induced phosphorylation of MEK1/2-ERK1/2ETS-like transcription factor-1 cascade via CD36 in human TBCs.
	Tsuzuki et al. (128), 2016	CD36 may be expressed in the nasal cavity and binds to fatty aldehyde. Nasal CD36 can signal to olfactory neurons.
	Xavier et al. (131), 2016	CD36-deficient mice did not demonstrate changes in the organization of the olfactory epithelium but showed impaired preference for a lipid mixture odor. CD36-expressing neurons represent a distinct population of OSNs, which may have specific functions in olfaction.
FFAR4 (GPR120)	Costanzo et al. (144), 2019	FFAR4 in fungiform papillae may play a role in fat perception. FFAR4 expression was positively associated with FAT sensitivity. Increases in FFAR4 may also increase intestinal satiety signals, leading to reduced further fat intake.
GPR120	Ancel et al. (84), 2015	GPR120 is not necessary for fat-taste detection.
	Murtaza et al. (113), 2020	Select GPR120 agonist can trigger intracellular Ca2+ increases, induce MAPK phosphorylation, and modulate fatty acid preference. Therefore, GPR120 is involved in fat-taste pathway.
	Ozdener et al. (115), 2014	GPR120 is involved in amplifying transduction response. CD36 and GPR120 have nonoverlapping roles in TBC signaling during orogustatory perception of dietary lipids
	Sclafani et al. (123), 2015	Post-oral GPR40/120 signaling is not required to process IG fat infusions in food-baited spout training.
	Yasumatsu et al. (132), 2018	GPR120 antagonist caused suppressed CT nerve signaling and the reduction of maximal nerve responses in WT mice.
GPR84	Liu et al. (109), 2021	GPR84 is involved in taste detection of MCFAs in TBCs by triggering intracellular Ca2+ increases and membrane depolarization.
Gr64e, Gr64f, IR56d	Kim et al. (104), 2018	Gr64e is involved in fat chemosensation, but not direct receptor; another Gustatory receptor required for the behavioral and electrophysiological responses to FA detection.
	Tauber et al. (127), 2017	IR56d/Gr64f neurons are activated by medium-chain FAs and are necessary and sufficient for reflexive feeding response to FAs.
Olfr544	Wu et al. (130), 2017	Olfr544 orchestrates the metabolic interplay between liver and adipose tissue, mobilizing stored fats from adipose tissue and shifting fat preference.
OR4D2, OR51A7, OR2T34, OR2Y1	Ramos-Lopez et al. (75), 2019	OR4D2, OR51A7, OR2T34, and OR2Y1, along with several downstream signaling molecules (SLC8A1, ANO2, PDE2A, CALML3, GNG7, CALML6, PRKG1, and CAMK2D) regulate odor detection and signal transduction processes within the complete olfactory cascade.
Prep1	Ricci et al. (117), 2018	Prep1 deficiency alters olfactory morphofunctional integrity and olfaction-mediated eating behavior.
P2X2/P3X3	Bensalem et al. (87), 2020	TGR5 KOs show changes in fat preference and calcium signaling
TGR5	Camandola and Mattson (93), 2017	TLR4 promotes fat ingestion (FA endocytosis) and fat taste preference
TRPC3	Murtaza et al. (114), 2021	TRPC3 KO mice TBCs showed significantly curtailed Ca2+ signaling in response to LA.

BMI, body mass indes; HFD, high-fat diet; WT, wild type; CD36, cluster of differentiation 36; GPR120, G protein-coupled receptor 120; TLR4, Toll-loke receptor 6; FAs, fatty acids; LA, linoleic acid; TBCs, taste bud cells; MCFAs, medium-chain fatty acids.