CD36 as a lipid sensor

International audience; CD36 is a multifunctional protein homologous to the class B scavenger receptor SR-B1 mainly found in tissues with a sustained lipid metabolism and in several hematopoieic cells. CD36 is thought to be involved in various physiological and pathological processes like angiogenesis, thrombosis, atherogenesis, Alzheimer's disease or malaria. An additive emerging function for CD36 is a role as a lipid sensor. Location of CD36 and orthologue molecules in plasma membrane of cells in contact with the external environment (e.g. gustatory, intestinal or olfactory epithelia) allows the binding of exogenous-derived ligands including dietary lipids, diglycerides from bacterial wal…

O24 Obésité et perception oro-sensorielle des lipides alimentaires : impact sur la triglycéridémie et le taux de cholécystokinine

Resveratrol, a chemopreventive agent, disrupts the cell cycle control of human SW480 colorectal tumor cells

Resveratrol is a natural polyphenolic compound produced by a number of plants and found in high amount in peanuts, seeds, grapes or berries as source of human nutrition. Epidemiological studies strongly suggest that resveratrol may act as a cancer chemopreventive compound. The mechanism by which resveratrol inhibits cell proliferation was studied in human colorectal tumor SW480 cell line. The results show that resveratrol strongly inhibits cell proliferation at the micromolar range in a time- and dose-dependent manner. Resveratrol appears to block the cell cycle at the transition --> G2/M since inhibition of [(3)H]-thymidine incorporation is not observed, while there is an increase of the c…

P129 L’obésité interfère avec la détection oro-sensorielle des acides gras à longue chaîne chez l’homme

L’obésité interfère avec la détection oro-senorielle des acides gras à longue chaîne chez l’homme

National audience

Ciprofibrate stimulates protein kinase C-dependent phosphorylation of an 85 kDa protein in rat Fao hepatic derived cells

The effect of ciprofibrate on early events of signal transduction was previously studied in Fao cells. Protein kinase C (PKC) assays performed on permeabilized cells showed a more than two-fold increase in PKC activity in cells treated for 24 h with 500 microM ciprofibrate. To show the subsequent effect of this increase on protein phosphorylation, the in vitro phosphorylation on particulate fractions obtained from Fao cells was studied. Among several modifications, the phosphorylation of protein(s) with an apparent molecular mass of 85 kDa was investigated. This modification appeared in the first 24 h of treatment with 500 microM ciprofibrate. It was shown to occur on Ser/Thr residue(s). It…

Molecular analysis on the chemopreventive properties of resveratrol, a plant polyphenol microcomponent.

As a plant microcomponent, resveratrol is a polyphenolic compound produced by several species and found especially in Polygonum roots, peanuts seeds, berries and also grape and therefore can be present in human diet or beverages (red wine, for instance). Traditional chinese medicine and more recent epidemiological studies strongly suggested that resveratrol may act as a cancer chemopreventive compound. The biochemical mechanism by which resveratrol inhibits cell proliferation was provided by studies in numerous human cell lines including our work in hepatoblastoma HepG2 and colorectal tumor SW480 cells. The results show that resveratrol strongly inhibits cell proliferation at the micromolar…

The Lipid-Sensor Candidates CD36 and GPR120 Are Differentially Regulated by Dietary Lipids in Mouse Taste Buds: Impact on Spontaneous Fat Preference

BACKGROUND: Recent studies in rodents and humans suggest that the chemoreception of long-chain fatty acids (LCFA) in oral cavity is involved in the spontaneous preference for fatty foods and might contribute to the obesity risk. CD36 and GPR120 are LCFA receptors identified in rodent taste bud cells. The fact that CD36 or GPR120 gene inactivation leads to a decrease in the preference for lipids raises the question of the respective role(s) played by these gustatory lipid-sensor candidates. METHODOLOGY/PRINCIPAL FINDINGS: Using a combination of biochemical, nutritional and behavioural studies in wild-type, CD36(+/-)and CD36(-/-) mice, it was found that: 1°) CD36 and GPR120 display different …

Simultaneous Inhibition of Peripheral CB1R and iNOS Mitigates Obesity-Related Dyslipidemia Through Distinct Mechanisms.

Diabetic dyslipidemia, characterized by increased plasma triglycerides and decreased HDL cholesterol levels, is a major factor contributing to nonalcoholic steatohepatitis and cardiovascular risk in type 2 diabetes. Activation of the cannabinoid-1 receptor (CB1R) and activation of inducible nitric oxide synthase (iNOS) are associated with nonalcoholic steatohepatitis progression. Here, we tested whether dual-targeting inhibition of hepatic CB1R and iNOS improves diabetic dyslipidemia in mice with diet-induced obesity (DIO mice). DIO mice were treated for 14 days with (S)-MRI-1867, a peripherally restricted hybrid inhibitor of CB1R and iNOS. (R)-MRI-1867, the CB1R-inactive stereoisomer that …

Taste of Fat: A Sixth Taste Modality?

International audience; An attraction for palatable foods rich in lipids is shared by rodents and humans. Over the last decade, the mechanisms responsible for this specific eating behavior have been actively studied, and compelling evidence implicates a taste component in the orosensory detection of dietary lipids [i.e., long-chain fatty acids (LCFA)], in addition to textural, olfactory, and postingestive cues. The interactions between LCFA and specific receptors in taste bud cells (TBC) elicit physiological changes that affect both food intake and digestive functions. After a short overview of the gustatory pathway, this review brings together the key findings consistent with the existence…

The oral lipid sensor GPR120 is not indispensable for the orosensory detectionof dietary lipids in the mouse

International audience; Implication of the long-chain fatty acid (LCFA) receptor GPR120, also termed free fatty acid receptor 4 (FFAR4), in the taste-guided preference for lipids is a matter of debate. To further unravel the role of GPR120 in the "taste of fat", the present study was conducted on GPR120-null mice and their wild-type littermates. Using a combination of morphological (i.e. immunohistochemical staining of circumvallate papillae - CVP), behavioral (i.e. two-bottle preference tests, licking tests and conditioned taste aversion) and functional studies (i.e. calcium imaging in freshly isolated taste bud cells - TBC), we show that absence of GPR120 in oral cavity was not associated…

Is the taste of fat regulated?

Over the last decade, converging data have been accumulated both in rodents and humans, supporting the existence of a sixth taste modality devoted to the perception of dietary lipids. It is well known that the sense of taste is determinant for the food choice and that the overconsumption of highly palatable energy-dense foods contributes to the current obesity epidemic. Thus, an important issue in terms of Public Health is to understand the mechanisms by which the oro-sensory perception of fat is regulated. An overview of our current knowledge in this field of investigations is proposed in this mini-review.

P208: La chute de la détection oro-sensorielle des lipides alimentaires chez la souris obèse a-t-elle une origine inflammatoire ?

Introduction et but de l’etude Nous avons recemment montre qu’une obesite induite chez la souris par un regime riche en acides gras satures perturbe la detection oro-sensorielle des lipides alimentaires. En effet, les souris obeses deviennent incapables de detecter correctement la presence de faibles concentrations de lipides lors de tests de double choix. Une correlation inverse entre masse grasse et seuil de detection orale des lipides a ete trouvee. Ce phenomene, dont l’origine est un dysfonctionnement de la cascade de signalisation CD36 dependante dans la papille gustative caliciforme (CVP), est reversible puisqu’une perte de masse grasse induite par une restriction calorique permet une…

Obesity interferes with the orosensory detection of long-chain fatty acids in humans

Background: The association between the orosensory detection of lipids, preference for fatty foods, and body mass index (BMI; in kg/m 2 ) is controversial in humans. Objective: We explored the oral lipid-sensing system and the orosensory-induced autonomic reflex system in lean and obese subjects. Design: Lean (BMI: 19 to ,25; n = 30) and obese (BMI .30; n = 29) age-matched men were enrolled. Their oral threshold sensitivity to linoleic acid (LA) was determined by using a 3-alternative forced-choice ascending procedure, and their eating habits were established by the analysis of 4 consecutive 24-h food-consumption diaries. The effect of brief oral lipid stimulations on plasma triglyceride [(…

CD36 involvement in orosensory detection of dietary lipids, spontaneous fat preference, and digestive secretions

International audience; Rats and mice exhibit a spontaneous attraction for lipids. Such a behavior raises the possibility that an orosensory system is responsible for the detection of dietary lipids. The fatty acid transporter CD36 appears to be a plausible candidate for this function since it has a high affinity for long-chain fatty acids (LCFAs) and is found in lingual papillae in the rat. To explore this hypothesis further, experiments were conducted in rats and in wild-type and CD36-null mice. In mice, RT-PCR experiments with primers specific for candidate lipid-binding proteins revealed that only CD36 expression was restricted to lingual papillae although absent from the palatal papill…

PPARs as physiological sensors of fatty acid metabolism molecular regulation in peroxisomes

Obesity alters the gustatory perception of lipids in the mouse: plausible involvement of lingual CD36. : Obesity decreases the fat preference

International audience; A relationship between orosensory detection of dietary lipids, regulation of fat intake, and body mass index was recently suggested. However, involved mechanisms are poorly understood. Moreover, whether obesity can directly modulate preference for fatty foods remains unknown. To address this question, exploration of the oral lipid sensing system was undertaken in diet-induced obese (DIO) mice. By using a combination of biochemical, physiological, and behavioral approaches, we found that i) the attraction for lipids is decreased in obese mice, ii) this behavioral change has an orosensory origin, iii) it is reversed in calorie-restricted DIO mice, revealing an inverse …

P073 L’obésité diminue, de manière réversible, la préférence pour les lipides alimentaires chez la souris

International audience; Introduction et but de l’étude. – Au cours des dernières années, il a été suggéré l’existence d’un lien étroit entre la détection oro-sensorielle des lipides alimentaire, la régulation de la prise alimentaire et l’IMC. Toutefois, les mécanismes affectant la sensibilité aux lipides ainsi que l’éventuelle implication directe de l’obésité restent mal connus.

CK36, un sérieu jalon sur la piste du goût du gras

Rôle des lipides dans la régulation du comportement alimentaire

Obesity constitutes a major public health problem for the 21 st Century, with its epidemic spread worldwide, particularly in children. The overconsumption of fatty foods greatly contributes to this phenomenon. Rodents and humans display a spontaneous preference for lipid-rich foods. But why are lipids so attractive? What are the molecular mechanisms involved? The purpose of this mini review is to explore few basic questions raised by recent data providing evidences on the relationships between dietary lipids and feeding behavior.

Sur la piste du « goût du gras »

Sense of taste informs the body about the quality of ingested foods. Five sub-modalities allowing the perception of sweet, salty, sour, bitter, and umami stimuli are classically depicted in Human. However, the spontaneous attraction of mammals for fatty foods raises the possibility of an additional oro-sensory modality devoted to the fat perception. During a long time, oro-sensory perception of dietary lipids was thought to take place only through textural and retronasal olfactory cues. This minireview analyses recent findings showing that the gustation can also play a significant role in the dietary lipid perception.

CD36 is regulated by dietary lipids in mouse circumvallate papillae. Impact on spontaneous fat preference

Orosensory Perception of Dietary Lipids in Mammals

Obesity constitutes a major public health problem for the twenty-first century, with its epidemic spread worldwide, particularly in children. The overconsumption of fatty foods greatly contributes to this phenomenon. Rodents and humans display a spontaneous preference for lipid-rich foods. However, the molecular mechanisms underlying this pattern of eating behaviour in mammals remain unclear. The orosensory perception of dietary lipids was long thought to involve only textural and olfactory cues. Recent findings challenge this limited viewpoint, strongly suggesting that the sense of taste also plays a significant role in dietary lipid perception and might therefore be involved in the prefer…

Role of CD36 in Oral and Postoral Sensing of Lipids

Obesity and associated plethora of diseases constitute a major public health challenge worldwide. The conjunction of profound changes in our lifestyle and a thrifty genetic that evolved in an environment of food scarcity largely explains this epidemic situation. Food abundance promotes our specific appetite for the more palatable food generally rich in lipids. It is noteworthy that this attraction for fatty food is not specific to humans. Rats and mice also spontaneously prefer lipid-rich food in a free-choice situation. Detection of lipids in food requires the presence of specific sensors located in strategic places (e.g., oral cavity, small intestine, brain) whose activation results in a …

CD36, un sérieux jalon sur la piste du goût du gras

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Lipid-mediated release of GLP-1 by mouse taste buds from circumvallate papillae: putative involvement of GPR120 and impact on taste sensitivity

Glucagon-like peptide-1 (GLP-1) signaling modulates sweet-taste sensitivity in the mouse. Because circumvallate papillae (CVPs) express both GLP-1 and its receptor, a local regulation has been suggested. However, whether dietary lipids are involved in this regulation, as shown in the gut, is unknown. By using a combination of biochemical, immunohistochemical, and behavioral approaches, the present data i) confirm the role of GLP-1 signaling in the attraction for sucrose, ii) demonstrate that minute quantities of long-chain FAs (LCFAs) reinforce the attraction for sucrose in a GLP-1 receptor-dependent manner, iii) suggest an involvement of the LCFA receptor GPR120 expressed in taste buds in …

Peroxisome-proliferator-activated receptors as physiological sensors of fatty acid metabolism: molecular regulation in peroxisomes

The enzymes required for the beta-oxidation of fatty acyl-CoA are present in peroxisomes and mitochondria. Administration of hypolipidaemic compounds such as clofibrate to rodents leads to an increase in the volume and density of peroxisomes in liver cells. These proliferators also induce simultaneously the expression of genes encoding acyl-CoA oxidase, enoyl-CoA hydratase-hydroxyacyl-CoA dehydrogenase (multifunctional enzyme) and thiolase (3-ketoacyl-CoA thiolase). All these enzymes are responsible for long-chain and very-long-chain fatty acid beta-oxidation in peroxisomes. Similar results were observed when rat hepatocytes, or liver-derived cell lines, were cultured with a peroxisome prol…

Impacts of obesity on the oro-sensory perception of lipids in Human

Accumulating evidences support the existence of a fatty acid taste both in rodents and humans. A recent study performed in lean subjects suggests the existence of a positive correlation between the oro-sensory perception of dietary lipids and body mass index (BMI) in Human. It was extrapolated that obesity might promote overconsumption of fatty foods by decreasing the detection of lipids in oral cavity. To explore this hypothesis, linoleic acid (LA) detection threshold was determined in lean (18>BMI 30, n=29) volunteers using a 3-alternative force choice ascending concentration presentation procedure in conditions known to minimize other sensory cues. A large distribution of LA detection wa…

Impact of long chain fatty acids on sweet taste sensitivity in mice. Role of the GPR120/GLP-1 signaling

Mécanismes de la perception gustative des lipides alimentaires

> L’obesite constitue indeniablement un des problemes majeurs de sante publique de ce debut du XXIe siecle. Sa prevalence est en constante augmentation notamment chez les enfants. Ce constat n’est pas anodin car l’obesite est souvent associee a diverses pathologies graves (atteintes vasculaires, diabete de type 2, hypertension, cancer). L’opulence alimentaire, en nous permettant de satisfaire nos appetits specifiques, contribue a ce phenomene. C’est ainsi que dans le regime occidental, les lipides alimentaires representent pres de 40 % des apports caloriques journaliers alors que les recommandations nutritionnelles sont inferieures de 5 a 10 %. L’origine de cette attirance pour les corps gr…

Perception gustative des lipides alimentaires

Resume Les grandes mutations techniques et economiques du XXe siecle ont eu de profondes repercutions sur notre facon de nous alimenter. Pour la premiere fois de son histoire, une large partie de la population mondiale « ne court plus apres les calories ». L’opulence alimentaire a une consequence evidente : elle laisse libre cours a nos appetits specifiques. C’est ainsi que dans le regime occidental, les lipides alimentaires representent pres de 40 % des apports caloriques journaliers alors que les recommandations nutritionnelles sont inferieures de 5 a 10 %. Cet apport excessif, associe a un desequilibre qualitatif (exces d’acides gras satures et de cholesterol, rapport des acides gras pol…

P060 Étude comparative par immunolocalisation des lipido-récepteurs CD36 et GPR120 dans la papille caliciforme de souris