CD36 is a transmembrane protein that is involved in the recognition of certain amphiphilic molecules such as polar lipids in various tissues and body fluids. So far, CD36 homologues in insects have been demonstrated to be present on the surface of olfactory dendrites and to participate in the perception of exogenous compounds. However, little is known about the relationship between CD36 and mammalian olfaction. Indeed, the detection of only CD36 mRNA in the mouse olfactory epithelium has been reported to date. In the present study, to provide potential pieces of evidence for the involvement of CD36 in mammalian olfactory perception, we extensively investigated the localisation of this protein in the mouse olfactory mucosa. In situ hybridisation analysis using antisense oligonucleotides to CD36 mRNA detected aggregated signals within the deeper epithelial layer of olfactory mucosa. The mRNA signals were also detected consistently in the superficial layer of the olfactory epithelium, which is occupied by supporting cells. Immunostaining with an anti-CD36 polyclonal antibody revealed that CD36 localises in the somata and dendrites of distinct olfactory receptor cells and that it occurs abundantly on the olfactory epithelial surface. However, immunoreactive CD36 was rarely detectable in the nerve bundles running in the lamina propria of olfactory mucosa, the axons forming the olfactory nerve layer in the outermost layer of the bulb and axon terminals in the glomeruli. We also obtained electron microscopic evidence for the association of CD36 protein with olfactory cilia. Altogether, we suggest that CD36 plays a role in the mammalian olfaction. In addition, signals for CD36 protein were also detected on or around the microvilli of olfactory supporting cells and the cilia of nasal respiratory epithelium, suggesting a role for this protein other than olfaction in the nasal cavity.

CD36 is a broadly expressed transmembrane protein that engages multiple ligands, including polar lipids. This protein is thought to even contribute to the chemosensory detection of long-chain fatty acids in the oral cavity of rodents. In this study, we assessed whether animals consciously perceive a ligand of CD36, 1-(palmitoyl)-2-(5-keto-6-octanedioyl)phosphatidylcholine (KOdiA-PC), and if so, whether CD36 is involved in sensing the oxidised phospholipid species. We found that mice avoided or hesitated to ingest fluids containing KOdiA-PC, suggesting a conscious perception of the lipid in the animals. We assessed the involvement and role of CD36 in the KOdiA-PC perception by comparing the behavioural responses of wild-type and CD36-deficient mice to the test fluids, and provided evidence that the protein could play a role in sensing a lower level of the lipid. We also found that transection of the olfactory nerve of wild-type mice resulted in an inability to perceive KOdiA-PC, suggesting the significance of olfactory system in the lipid sensing. Our findings, coupled with the recent finding of CD36 expression in the mouse olfactory epithelium, led us to predict that the site of CD36 action in the KOdiA-PC sensing plausibly lies within the nasal cavity of the animal.Animals have highly developed chemosensory systems that enable efficient detection of diverse soluble or volatile molecules. Detection of exogenous molecules by taste bud cells and/or olfactory receptor cells transmits signals to the brain and consequently induces various behavioural responses (e.g., appetitive or aversive response to foods) (21, 25). To better understand the mechanisms underlying chemosensory perception, much effort has gone into identifying sensory proteins in the oral and nasal cavities (4, 5). CD36 is a broadly expressed transmembrane protein associated with the recognition of multiple molecules (e.g., amphipathic lipids) (15,19). For instance, in macrophages, CD36 contributes to the clearance of oxidised forms of low-density lipoprotein from the blood by recognising distinct phospholipid species on the surface of the particles (6,20). Furthermore, CD36 expressed by enterocytes is believed to participate in not only recognition and absorption of long-chain fatty acids but also in formation of chylomicrons (18). In addition to its well-characterized functions, CD36 has been postulated to play an important role in the chemosensory detection of longchain fatty acids in the oral cavity, leading to an appetitive response to the lipid species in rodents. Several lines of evidence support this finding: CD36 is localised to the apical surface of taste bud cells in

Class B scavenger receptors, scavenger receptor B1 (SR-B1) and cluster of differentiation 36 (CD36), are broadly expressed cell-surface proteins and are believed to serve as multifaceted players in lipid and lipoprotein metabolism in mammals. Because of its ability to recognise distinct odour-active volatile compounds and its presence in murine olfactory epithelium, CD36 has recently emerged as a participant in the detection of odorants within the nasal cavity. However, there have been no attempts to assess whether SR-B1 has such a role. In this study, we performed a cell-free in-vitro assay utilising a peptide mimic of the receptor, and demonstrated that SR-B1 could recognise aliphatic aldehydes (e.g., tetradecanal), a distinct class of volatile odorants, as potential ligands. By reverse transcription-polymerase chain reaction and western immunoblot analyses, we detected the expression of SR-B1 mRNA and protein, respectively, in mouse olfactory tissue. Finally, we immunohistochemically mapped the distribution of SR-B1 in the surface layer of olfactory epithelium in vivo, which is the first line of odorant detection. These findings uncover a novel role for SR-B1 as a contributor to the capture of specific odorants in the nasal cavity of mammals.Class B scavenger receptors are cell-surface proteins, characterised by two predicted transmembrane spans, broad expression patterns and the ability to recognise diverse ligands (13). Of these, scavenger receptor B1 (SR-B1) was initially identified as comprising 509 amino-acid residues (5). An earlier study has showed that SR-B1 is expressed in several tissues including the liver and adipose tissues, and can serve as a receptor for low-density lipoprotein (LDL), acetylated LDL, oxidised LDL (oxLDL) and maleylated bovine serum albumin (BSA) (2). Later, SR-B1 was found to recognise several other substances such as high-density lipoprotein (HDL) (1) and anionic phospholipids (15). These findings suggested that SR-B1 primarily participates in lipid and lipoprotein metabolism in internal organs (36). As studied extensively, it functions as a physiologically relevant HDL receptor to mediate the selective delivery of HDL-cholesterol (i.e., HDL-cholesteryl ester) to the liver and steroidogenic tissues (1,13,20). Another member of class B scavenger receptors, cluster of differentiation 36 (CD36), which comprises 472 amino-acid residues, is also a multifaceted and multifunctional player in lipid and lipoprotein metabolism (13,27,28). CD36 is known to share with SR-B1 the ability to recognise distinct ligands,

Cluster of differentiation 36 (CD36) is a broadly expressed transmembrane receptor that has multiple ligands. It has been found to occur abundantly on the surface of the olfactory epithelium in mice and postulated to play a role in mammalian olfaction. However, there have been no ethological analyses of the mammalian behaviour showing CD36 involvement in the olfactory perception of a distinct odour-active volatile compound. In this study, we aimed to assess whether mammals perceive oleic aldehyde, an odour-active volatile that serves as a potential CD36 ligand, and if so, whether CD36 is involved in the sensing by following measurements using CD36-knockout mice and their wild-type littermates. In a two-bottle choice test, wild-type mice, but not CD36-knockout mice, discriminated a sucrose solution containing oleic aldehyde from the sucrose solution alone. To assess the importance of the olfactory system in the oleic aldehyde perception, we conducted an exploration test where the animals could rely primarily on the odour of test volatiles for recognition. We found that the wild-type, but not CD36-knockout mice, were aware of the compound. Our results provide behavioural evidence that CD36 plays a role in the perception of specific odour-active volatile compounds in the nasal cavity.Chemosensory systems are responsible for the detection of soluble and volatile chemicals. The two chemosensory systems in mammals, gustatory and olfactory systems, distinguish nutritive compounds from harmful ones within the oral and nasal cavities (10). The sense of smell is particularly important for avoiding harmful chemicals in foods prior to ingestion (7). The olfactory perception starts from the binding of odorants to specific G-protein-coupled receptors on olfactory sensory neurons located within the olfactory epithelium of the nasal cavity (5). However, for many odorants, the precise mechanisms of olfactory detection in mammals remain to be studied. Cluster of differentiation 36 (CD36) is a membrane-bound receptor with two transmembrane spans that is produced and expressed by a variety of sites in the body of vertebrates (23). The receptor is involved in lipid binding and uptake within tissues, such as the small intestinal, adipose and muscle tissues (6). CD36 has also been postulated to play roles in the gustatory system. Indeed, CD36 has been shown to mediate the detection of long-chain fatty acids in the oral cavity, driving the consumption of the lipid species in rodents (12, 16). More

Most animals, including humans, have a high avidity for consuming dietary fat. Previous studies have reported that fat preference can be attributed to many factors, including palatable flavor, texture, and chemical perception. Moreover, transection of nerves associated with either olfaction or gustation (i.e., olfactory or glossopharyngeal nerve) has been shown to decrease fat ingestion (1-3). In the central nervous system, several studies have suggested that the opioid system, canonically associated with reward circuitry, is associated with dietary preferences for fat. We recently reported that fat ingestion induces elevations in the endogenous opioid peptide, beta-endorphin, in cerebrospinal fluid (4). Furthermore, we have also demonstrated that fat ingestion can activate pro-opiomelanocortin (POMC) neurons in the hypothalamus, which synthesize beta-endorphin (5). Many reports have suggested that administration of opioid receptor antagonists can attenuate fat preference, an observation that is consistent with our findings (4,(6)(7)(8).A significant amount of experimental evidence implicates the opioid system in the reward and reinforcement of drug addiction. We previously demonstrated that, similar to drug administration, fat ingestion can serve as a reinforcer by inducing place preference or strong lever-pressing behavior in mice (we define these as "reinforcing effects") (9, 10). Moreover, it has been reported that opioid receptor antagonists can diminish the reinforcing influence of fat (11). These findings suggest that the opioid system contributes not only to fat preference, but also to reinforcement. However, the concentration of fat that produces a reinforcing effect might differ from that inducing preference behavior. Indeed, while mice prefer fat even at low concentrations (12), the reinforcing property of fat is only observed in response to substances with higher fat content (13). These findings indicate that the mechanisms underlying preference for fat are distinctly dependent on fat content. Since POMC neurons regulate energy homeostasis modulating feeding and/or energy expenditure (14-17), the opioid system might have an influence on the preference for high fat concentrations.It also seems likely that several nerves (i.e., the chorda tympani, glossopharyngeal, and trigeminal nerves) are involved in recognizing the presence of dietary fat in the oral cavity. In particular, the glossopharyngeal nerve contributes to preference behavior associated with high concentrations of fat, since glossopharyngeal nerve transection (GLX) can partially inhibit POMC neurons that have been activated by fat ingestion (5). Conversely, olfactory nerve transection (ONX) can abolish the preference for low fat concentrations (18); thus, olfactory and gustatory transduction related to fat preference might rely on fat concentration in a different manner. Summary High-fat foods tend to be palatable and can cause addiction in mice via a reinforcing effect. However, mice showed preference for low fat concentrations that do not...