Medium-chain triglyceride-specific appetite is regulated by the ß-oxidation of medium-chain fatty acids in the liver.

Most studies on fat appetite have focused on long-chain triglycerides (LCTs) due to their obesogenic properties. Medium-chain triglycerides (MCTs), conversely, exhibit antiobesogenic effects; however, the regulation of MCT intake remains elusive. Here, we demonstrate that mice can distinguish between MCTs and LCTs, and the specific appetite for MCTs is governed by hepatic ß-oxidation. We generated liver-specific medium-chain acyl-CoA dehydrogenase (MCAD)-deficient (MCADL-/-) mice and analyzed their preference for MCT and LCT solutions using glyceryl trioctanoate (C8-TG), glyceryl tridecanoate (C10-TG), corn oil, and lard oil in two-bottle choice tests conducted over 8 days. In addition, we used lick microstructure analyses to evaluate the palatability and appetite for MCT and LCT solutions. Finally, we measured the expression levels of genes associated with fat ingestion (Galanin, Qrfp, and Nmu) in the hypothalamus 2 h after oral gavage of fat. Compared with control mice, MCADL-/- mice exhibited a significantly reduced preference for MCT solutions, with no alteration in the preference for LCTs. Lick analysis revealed that MCADL-/- mice displayed a significantly decreased appetite for MCT solutions only while the palatability of both MCT and LCT solutions remained unaffected. Hypothalamic Galanin expression in control mice was elevated by oral gavage of C8-TG but not by LCTs, and this response was abrogated in MCADL-/- mice. In summary, our data suggest that hepatic ß-oxidation is required for MCT-specific appetite but not for LCT-specific appetite. The induction of hypothalamic galanin upon MCT ingestion, dependent on hepatic ß-oxidation, could be involved in the regulation of MCT-specific appetite.NEW & NOTEWORTHY Whether and how medium-chain triglyceride (MCT) intake is regulated remains unknown. Here, we showed that mice can discriminate between MCTs and LCTs. Hepatic ß-oxidation participates in MCT-specific appetite, and hypothalamic galanin may be one of the factors that regulate MCT intake. Because of the antiobesity effects of MCTs, studying MCT-specific appetite may help combat obesity by promoting the intake of MCTs instead of LCTs.

Binding Interaction Between Lauric Acid and Cluster of Differentiation 36 Underpinned by a Fluorescence- Intensifying Assay.

Cluster of differentiation 36 (CD36) is a scavenger receptor expressed in various vertebrate cells that contains diverse ligands, including long-chain fatty acids. This receptor has recently been suggested as a captor of specific volatile odorants (e.g., aliphatic acetates) in the mammalian nasal epithelium. This study used a fluorescence-intensifying assay to produce the first evidence that lauric acid, an odorous fatty acid, directly binds to CD36. This expansion of the repertoire of volatile ligands supports potential applications for nasal CD36. Our present findings could promote future research aimed at understanding the mechanisms of fatty acid interactions with CD36.

A point of view on human fat olfaction - do fatty derivatives serve as cues for awareness of dietary fats?

Fat (triglycerides) consumption is critical for the survival of animals, including humans. Being able to smell fat can be advantageous in judging food value. However, fat has poor volatility; thus, olfaction of fat seems impossible. What about fatty acids that comprise fat? Humans smell and discriminate medium-chain fatty acids. However, no conclusive evidence has been provided for the olfactory sense of long-chain fatty acids, including essential acids such as linoleic acid (LA). Instead, humans likely perceive the presence of essential fatty acids through the olfaction of volatile compounds generated by their oxidative breakdown (e.g., hexanal and γ-decalactone). For some people, such scents are pleasing, especially when they come from fruit. Nonetheless, it remains unclear whether the olfaction of these volatiles leads to the recognition of fat per se. Nowadays, people often smell LA-borne aldehydes such as E,E-2,4-decadienal that occur appreciably, for example, from edible oils during deep frying, and are pronely captivated by their characteristic "fatty" note, which can be considered a "pseudo-perception" of fat. However, our preference for such LA-borne aldehyde odors may be a potential cause behind the modern overdose of n-6 fatty acids. This review aims to provide a view of whether and, if any, how we olfactorily perceive dietary fats and raises future purposes related to human fat olfaction, such as investigating sub-olfactory systems for detecting long-chain fatty acids.

Application of a novel fluorescence intensity assay: identification of distinct fatty acetates as volatile compounds that bind specifically to amino acid region 149-168 of a transmembrane receptor CD36.

The cluster of differentiation 36 (CD36) is a transmembrane receptor expressed in various cells and has diverse lipid ligands. The expression of CD36 in the murine olfactory epithelium and its ability to recognize certain species of fatty aldehydes, a class of odor-active volatile compounds, have suggested a role for this receptor in the capture of specific odorants in the nasal cavity of mammals. However, the spectrum of CD36-recognizable volatile compounds is poorly understood. In this study, we employed our recently devised assay with fluorescently labeled peptides as probes (fluorescence intensity assay) and identified distinct fatty acetates as volatile compounds that bind specifically to amino acid region 149-168 of CD36 (eg dodecyl and tetradecyl acetates). The present findings demonstrate the utility of our assay for the discovery of novel CD36 ligands and support the notion that the receptor functions as a captor of volatile compounds in the mammalian olfactory system.

Assessment of direct binding interaction between CD36 and its potential lipid ligands using a peptide mimic of the receptor labeled with a fluorophore.

Cluster of differentiation 36 (CD36) is a cell-surface receptor that recognizes diverse substances. We have presented indirect evidence that a short segment of the receptor comprising amino acids 149-168 contains a site for binding of its lipid ligands (e.g., distinct fatty acids and aldehydes). However, experimental support for their direct interactions is yet to be achieved. For this, we devised a fluorescence intensity assay, where a synthetic peptide consisting of CD36 amino acids 149-168 labeled with fluorescein isothiocyanate (FITC-CD36149-168) and its variant peptides were used as positive and negative probes, respectively. First, we obtained results indicating that 1-palmitoyl-2-(5-keto-6-octenedioyl)phosphatidylcholine (an established CD36 ligand) but not 1-palmitoyl-2-arachidonyl-phosphatidylcholine (a non-ligand of the receptor) bound in a saturable and specific manner to FITC-CD36149-168. Strikingly, the assay allowed us to provide the first evidence supporting direct and specific binding between the CD36 segment and fatty aldehydes (e.g., Z-11-hexadecenal). However, this method failed to illustrate specific interactions of the segment with fatty acids, such as oleic acid. Nonetheless, our findings offer further insight into the biologically relevant ligands and the role of CD36. In addition, we suggest that this fluorescence-based technique provides a convenient means to evaluate protein (peptide)-lipid interactions.

Higher Straight-Chain Aliphatic Aldehydes: Importance as Odor-Active Volatiles in Human Foods and Issues for Future Research.

Owing to their apparent lack of health significance, higher straight-chain aliphatic aldehydes, i.e., those having alkyl chains with more than six carbon atoms, have been largely neglected in food and nutraceutical research. However, they are an important class of odor-active volatiles in human foods. Indeed, certain aldehydes, such as hexanal, E-2-nonenal, and E, E-2,4-decadienal, serve as key odorants in a range of our foods and drinks. This perspective describes the significance of higher straight-chain aliphatic aldehydes as food odorants, focusing on several representative ones, and raises the issues regarding these aldehydes to be addressed in the future.

A role for scavenger receptor B1 as a captor of specific fatty acids in taste buds of circumvallate papillae.

Class B scavenger receptor family members, scavenger receptor B1 (SR-B1) and cluster of differentiation 36 (CD36), are broadly expressed cell-surface proteins, both of which are believed to serve as multifaceted players in lipid and lipoprotein metabolism in mammals. Because of its presence in the apical part of taste receptor cells within circumvallate taste buds and its ability to recognise long-chain fatty acids, CD36 has been believed to participate in the sensing of the lipid species within the oral cavity. However, there have been no attempts to address whether SR-B1 has such a role to date. In this study, by reverse transcription- polymerase chain reaction analysis, we detected SR-B1 mRNA in a total RNA sample isolated from the circumvallate papillae of mouse tongue. Immunohistochemical analysis of tongue sections from the animals revealed the expression of SR-B1 protein in a population of taste bud cells of circumvallate papillae. In addition, the pattern of staining in the papillae for SR-B1 agreed closely with that for CD36 in double immunostaining analysis. We performed a cell-free in-vitro assay utilising a peptide mimic of SR-B1 and provided evidence that the receptor could recognise certain of the unsaturated long-chain fatty acids such as oleic acid. Our present findings suggest an additional role for SR-B1 as a captor of specific fatty acids in the oral cavity of mammals and contribute to expanding our knowledge of the physiological function of the receptor.

A novel role for scavenger receptor B1 as a contributor to the capture of specific volatile odorants in the nasal cavity.

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.

A Search for CD36 Ligands from Flavor Volatiles in Foods with an Aldehyde Moiety: Identification of Saturated Aliphatic Aldehydes with 9-16 Carbon Atoms as Potential Ligands of the Receptor.

Volatile compounds with an aldehyde moiety such as (Z)-9-octadecenal are potential ligands for cluster of differentiation 36 (CD36), a transmembrane receptor that has recently been shown to play a role in mammalian olfaction. In this study, by performing an assay using a peptide mimic of human CD36, we aimed to discover additional ligands for the receptor from volatiles containing a single aldehyde group commonly found in human foods. Straight-chain, saturated aliphatic aldehydes with 9-16 carbons exhibited CD36 ligand activities, albeit to varying degrees. Notably, the activities of tridecanal and tetradecanal were higher than that of oleic acid, the most potent ligand among the fatty acids tested. Among the aldehydes other than aliphatic aldehydes, only phenylacetaldehyde showed a weak activity. These findings make a contribution to our knowledge of recognition mechanisms for flavor volatiles in foods with an aldehyde group.

CD36 involvement in the olfactory perception of oleic aldehyde, an odour-active volatile compound, in mice.

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.

Assessment of direct interaction between CD36 and an oxidized glycerophospholipid species.

Cluster of differentiation 36 (CD36) is a transmembrane protein that recognizes multiple diverse ligands. It is believed that (i) oxidized glycerophosphatidylcholine species having a terminal γ-hydroxyl(or oxo)-α,ß-unsaturated carbonyl on the sn-2 acyl group (oxGPCCD36), which can occur on the surface of lipoprotein particles, serve as high-affinity ligands for CD36, and (ii) the amino acid 150-168 of CD36 (CD36150-168) is responsible for recognizing oxGPCCD36. However, it remains uncertain whether CD36150-168 directly interacts with oxGPCCD36 alone. In this study, we addressed this issue by investigating and comparing the banding pattern by non-denaturing polyacrylamide gel electrophoresis of a glutathione S-transferase (GST) fusion protein containing CD36150-168 (GST-CD36150-168), in the presence and absence of an oxGPCCD36 species, 1-(palmitoyl)-2-(5-keto-6-octenedioyl)phosphatidylcholine (KOdiA-PC). It was shown that GST-CD36150-168 pre-incubated with KOdiA-PC produced bands at upper positions than did the fusion protein alone. Further analyses revealed that the bands produced by the loading of GST-CD36150-168/KOdiA-PC mixture represent complexes consisting of the fusion protein and lipid. To our knowledge, this is the first evidence for direct interaction between CD36150-168 and oxGPCCD36 alone. It is also notable that the electrophoresis-based technique provides a convenient means to evaluate protein-lipid interactions.

Identification of the odor-active volatile compound (Z,Z)-4,7-tridecadienal as a potential ligand for the transmembrane receptor CD36.

Cluster of differentiation 36 (CD36) is a broadly expressed transmembrane protein that has multiple ligands, including oxidized low-density lipoproteins. We found recently that CD36 is expressed in olfactory sensory neurons and postulated that it plays a role in the detection of distinct odorants in the nasal cavity. To date, however, there have been few examples of attempts to identify CD36-recognizable odorants. In this study, by an in vitro assay using a peptide mimic of the receptor, we provided evidence that CD36 recognizes (Z,Z)-4,7-tridecadienal, an odor-active volatile compound that is known to occur in Katsuobushi (dried, fermented, and smoked skipjack tuna commonly used in Japanese cuisine as a seasoning) and in the preorbital secretion of male oribi. In addition, by comparing the data with those of its related compounds, we provided information on the structural requirements of (Z,Z)-4,7-tridecadienal for recognition by CD36. For instance, we showed that flexible rotation around the C2-C3 bond of the volatile may be of importance in gaining access to CD36. Identification of (Z,Z)-4,7-tridecadienal as the ligand prompts us to hypothesize that CD36 could participate in the control of distinct mammalian behaviors (e.g., food selection) through its ability to recognize specific odorants in the environment.

Immunohistochemical localization of fatty acid transporters and MCT1 in the sebaceous glands of mouse skin.

The sebaceous glands secrete sebum to protect the epidermis and hairs by the oily products. The glands express several transporters and binding proteins for the production of fatty acids and uptake of their sources. The present immunohistochemical study examined the expression and localization of CD36, MCT1, FATP4, and E-FABP in the sebaceous glands, including the meibomian and preputial glands of mice. CD36 and MCT1 in sebaceous glands were largely co-localized along the plasma membrane of secretory cells, while they were separately expressed in the glandular portion of meibomian and preputial glands. Immunoreactivities for FATP4 and E-FABP appeared diffusely in the cytoplasm of secretory cells. Genetic deletion of CD36 did not affect the immunolocalization of the three other molecules. The sebaceous glands were judged to be useful for analyzing the functions and relation of fatty acid transporters and binding proteins.

A single aldehyde group can serve as a structural element for recognition by transmembrane protein CD36.

Transmembrane protein CD36 is considered to bind its distinct ligands such as long-chain fatty acids primarily by recognizing their terminal carboxyl moiety. In this study, we provide evidence that long-chain fatty aldehydes, such as oleic aldehyde, can be recognized by CD36. We suggest that a single aldehyde group may also serve as one of the structural elements recognizable by CD36.

A role of CD36 in the perception of an oxidised phospholipid species in mice.

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.

Dynamics of Optically-Generated Carriers in Si (100) and Si (111) Substrate-Grown GaAs/AlGaAs Core-Shell Nanowires.

GaAs/Al0.1Ga0.9As core-shell nanowires (CSNWs), with average lateral size of 125 nm, were grown on gold nanoparticle-activated Si (100) and Si (111) substrates via molecular beam epitaxy. Room temperature-photoluminescence (RT-PL) from the samples showed bulk-like GaAs and Al0.1Ga0.9As bandgap emission peaks at 1.43 and 1.56 eV, respectively. Higher PL emission intensity of the sample on Si (111) compared to that on Si (100) is attributed to uniform Al0.1Ga0.9As shell passivation of surface states on Si (111)-grown CSNWs. Carrier dynamics in two different temporal regimes were studied. In the sub-nanosecond time scale (300-500 ps), time-resolved radiative recombination efficiency of carriers was examined. In the 0-4 ps range, surface field-driven ballistic transport of carriers was probed in terms of the radiated terahertz (THz) waves. Time-resolved PL measurements at 300 K revealed that the carrier recombination lifetime of the GaAs core on Si (100)-grown CSNWs is 333 ps while that on Si (111)-grown sample is 500 ps. Ultrafast photoexcitation of GaAs core on the two samples generated a negligible difference in the intensity and bandwidth of emitted THz radiation. This result is ascribed to the fact that the deposited GaAs material on both substrates produced samples with comparable NW densities and similar GaAs core average diameter of about 75 nm. The samples' difference in GaAs core's carrier recombination lifetime did not influence THz emission since the two processes involve distinct mechanisms. The THz spectrum of CSNWs grown on Si (111) exhibited Fabry-Perot modes that originated from multiple reflections of THz waves within the Si substrate.

Mechanisms Involved in Guiding the Preference for Fat Emulsion Differ Depending on the Concentration.

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 elicit a reinforcing effect in a two-bottle choice test with water as the alternative. This behavior indicates the possibility that the mechanism underlying fat palatability may differ depending on the dietary fat content. To address this issue, we examined the influences of the opioid system and olfactory and gustatory transductions on the intake and reinforcing effects of various concentrations of a dietary fat emulsion (Intralipid). We found that the intake and reinforcing effects of fat emulsion were reduced by the administration of an opioid receptor antagonist (naltrexone). Furthermore, the action of naltrexone was only observed at higher concentrations of fat emulsion. The intake and the reinforcing effects of fat emulsion were also reduced by olfactory and glossopharyngeal nerve transections (designated ONX and GLX, respectively). In contrast to naltrexone, the effects of ONX and GLX were mainly observed at lower concentrations of fat emulsion. These results imply that the opioid system seems to have a greater role in determining the palatability of high-fat foods unlike the contribution of olfactory and glossopharyngeal nerves.

A matter of symmetry: terahertz polarization detection properties of a multi-contact photoconductive antenna evaluated by a response matrix analysis.

While terahertz time domain spectroscopy (THz-TDS) is a well-established technique, polarization sensitive measurements are challenging due to the need of broadband polarization devices. Here, we characterize our recently introduced multi-contact photoconductive detector antenna with a response matrix analysis. We show that the lead lines attached to electrodes reduce the antenna symmetry and thereby influence the properties of the response matrices. With a wire grid polarizer, we simulate a sample influencing the polarization angle and the intensity of the incident THz pulse. Evaluating the measurements with the response matrix analysis, our results show a well agreement of the adjusted and measured polarization angles and intensities over a frequency range from 0.25 to 0.8 THz.

Expression of CD36 by Olfactory Receptor Cells and Its Abundance on the Epithelial Surface in Mice.

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.