Intestinal conversion of linoleic acid to arachidonic acid in the rat

Abstract The arachidonic acid (C20:4, n-6) appearing in intestinal lymph during linoleic acid (C18:2, n-6) absorption may originate from enterocyte synthesis or from the liver either after secretion in biliary phospholipids at the same time dietary linoleic acid absorption occurs or via plasma. The radioactivity measured in the total bile collected during the 6 hours of linoleic acid absorption is too small to explain hepatic origin of the C20:4 detected by high performance liquid chromatography analysis of labeled fatty acids recovered in the lymph, in the intestinal mucosa, and the intestinal wall at the peak of linoleic acid intestinal absorption. This study confirms the probability that…

Inconsistency measuring over multisets of formulas

International audience; Measuring Inconsistency in Information : The concept of measuring inconsistency in information was developed by John Grant in a 1978 paper in the context of first-order logic. For more than 20 years very little was done in this area until in the early 2000s a number of AI researchers started to formulate new inconsistency measures primarily in the context of propositional logic knowledge bases. The aim of this volume is to survey what has been done so far, to expand inconsistency measurement to other formalisms, to connect it with related topics, and to provide ideas for further research in a topic that is particularly relevant now in view of the many inconsistencies…

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

Perception oro-sensorielle des lipides alimentaires et obésité

International audience; The gustation is a dynamic system able to rapid physiological adaptations in response to on-going environmental changes that characterize our feed (rhythm, quality, quantity). Based on the modulation of taste sensitivity thresholds, this homeostatic system contributes to build the feeding behavior by driving the food choices. Therefore, a dysfunction of this regulatory system might impact on dietary habits and thus, ultimately, on health. Consistent with this assumption, recent data report that a diet-induced obesity is associated both with a dysfunction of the oral fat detection system and a preferential consumption of fat-rich diets in rats and mice. In humans, a s…

CD36 is involved in lycopene and lutein uptake by adipocytes and adipose tissue cultures

International audience; Scope: Carotenoids are mainly stored in adipose tissue. However, nothing is known regarding the uptake of carotenoids by adipocytes. Thus, our study explored the mechanism by which lycopene and lutein, two major human plasma carotenoids, are transported. Methods and results: CD36 was a putative candidate for this uptake, 3T3-L1 cells were treated with sulfosuccinimidyl oleate, a CD36-specific inhibitor. sulfosuccinimidyl oleate-treated cells showed a significant decrease in both lycopene and lutein uptake as compared to control cells. Their uptake was also decreased by partial inhibition of CD36 expression using siRNA, whereas the overexpression of CD36 in Cos-1 cell…

CLA-Enriched Diet Containing t10,c12-CLA Alters Bile Acid Homeostasis and Increases the Risk of Cholelithiasis in Mice

International audience; Mice fed a mixture of CLA containing t10,c12-CLA lose fat mass and develop hyperinsulinemia and hepatic steatosis due to an accumulation of TG and cholesterol. Because cholesterol is the precursor in bile acid (BA) synthesis, we investigated whether t10,c12-CLA alters BA metabolism. In Expt. 1, female C57Bl/6J mice were fed a standard diet for 28 d supplemented with a CLA mixture (1 g/100 g) or not (controls). In Expt. 2, the feeding period was reduced to 4, 6, and 10 d. In Expt. 3, mice were fed a diet supplemented with linoleic acid, c9,t11-CLA, or t10,c12-CLA (0.4 g/100 g) for 28 d. In Expt. 1, the BA pool size was greater in CLA-fed mice than in controls and the …

BPA, an Energy Balance Disruptor

International audience; Bisphenol A (BPA) is used extensively in the world and is present in a diverse range of manufactured articles including dental resins, polycarbonate plastics, and the inner coating of food cans. It is a high volume chemical, with global production at 3.6 × 109 kg per year. BPA was identified as a high priority for assessment of human health risk because it was considered to present greatest potential for human exposure. Most studies of the health effects of BPA have focused on endocrine disruption leading to reproductive toxicity, but it displays additional side effects, including liver damage, disrupted pancreatic β-cell function, thyroid hormone disruption, and obe…

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

Lipides et obésité : aussi une histoire de goût ?

Resume La gustation est un systeme dynamique capable d’une adaptation physiologique rapide en reponse aux changements environnementaux permanents qui caracterisent notre alimentation (rythme, qualite, quantite). Base sur la modulation des seuils de sensibilite gustative, ce systeme homeostatique contribue a la construction du comportement alimentaire en orientant les choix de consommation. On peut donc penser qu’un dysfonctionnement de ce systeme regulateur peut avoir un impact sur les habitudes alimentaires et donc, a terme, sur la sante. La mise en evidence recente chez le rongeur (rat, souris) qu’une obesite induite par le regime non seulement entraine une deterioration de la detection o…

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 …

Muricholic Acids Promote Resistance to Hypercholesterolemia in Cholesterol-Fed Mice

International audience; Background and aims: Hypercholesterolemia is a major risk factor for atherosclerosis and cardiovascular diseases. Although resistant to hypercholesterolemia, the mouse is a prominent model in cardiovascular research. To assess the contribution of bile acids to this protective phenotype, we explored the impact of a 2-week-long dietary cholesterol overload on cholesterol and bile acid metabolism in mice. Methods: Bile acid, oxysterol, and cholesterol metabolism and transport were assessed by quantitative real-time PCR, western blotting, GC-MS/MS, or enzymatic assays in the liver, the gut, the kidney, as well as in the feces, the blood, and the urine. Results: Plasma tr…

CLA, “new nutrients”?

International audience; Conjugated linoleic acid (CLA) refers to a class of positional and geometric dienoic isomers of linoleic acid. Chronic dietary supplementation with commercial isomeric mixtures sold as dietary supplements leads to a drop in fat mass in various species. The t10,c12-CLA isomer is responsible for this antiobesity effect.The reduction of fat mass is especially dramatic in the mouse, in which it is associated with a severe hyperinsulinemia, an insulin resistance and a massive liver steatosis. The origin of these adverse side effects and the putative chronology of events leading to CLA-mediated lipoatrophic syndrome are presented and discussed in this review. In Human, the…

ERK1/2 activation in human taste bud cells regulates fatty acid signaling and gustatory perception of fat in mice and humans

Obesity is a major public health problem. An in-depth knowledge of the molecular mechanisms of oro-sensory detection of dietary lipids may help fight it. Humans and rodents can detect fatty acids via lipido-receptors, such as CD36 and GPR120. We studied the implication of the MAPK pathways, in particular, ERK1/2, in the gustatory detection of fatty acids. Linoleic acid, a dietary fatty acid, induced via CD36 the phosphorylation of MEK1/2-ERK1/2-ETS-like transcription factor-1 cascade, which requires Fyn-Src kinase and lipid rafts in human taste bud cells (TBCs). ERK1/2 cascade was activated by Ca2+ signaling via opening of the calcium-homeostasis modulator-1 (CALHM1) channel. Furthermore, f…

P059 Le lipido-récepteur intestinal CD36 et sa cascade de signalisation ERK1/2 dépendante contrôle la synthèse des chylomicrons

International audience; Introduction et but de l’étude. – L’intestin est capable d’adapter sa capacité d’absorption à la teneur en lipide du régime. Cette adaptation implique un système de détection des lipides au niveau entérocytaire. Le CD36, qui est une glycoprotéine transmembranaire liant avec une forte affinité les acides gras à longue chaîne (AGLC), pourrait jouer ce rôle. En effet, ex vivo, la présence d’AGLC est associée à une activation de la voie ERK1/2 et conduit à l’induction de protéines clés du métabolisme intestinal des lipides : l’ApoB48 et la MTP. Cette régulation est CD36 dépendante (Tran et al. 2011). De plus, la déficience de CD36 est associée chez l’Homme et l’animal à …

Induction of the fatty acid transport protein 1 and acyl-CoA synthase genes by dimer-selective rexinoids suggests that the peroxisome proliferator-activated receptor-retinoid X receptor heterodimer is their molecular target

The intracellular fatty acid content of insulin-sensitive target tissues determines in part their insulin sensitivity. Uptake of fatty acids into cells is a controlled process determined in part by a regulated import/export system that is controlled at least by two key groups of proteins, i.e. the fatty acid transport protein (FATP) and acyl-CoA synthetase (ACS), which facilitate, respectively, the transport of fatty acids across the cell membrane and catalyze their esterification to prevent their efflux. Previously it was shown that the expression of the FATP-1 and ACS genes was controlled by insulin and by peroxisome proliferator-activated receptor (PPAR) agonists in liver or in adipose t…

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…

CD36 and taste of fat.

Purpose of review This review explores the recent literature on the role of CD36 in the taste of fat, eating behavior and obesity risk in rodents and humans. Recent findings During the last decade, evidence was accumulated supporting the existence of a taste of fat responsible for the spontaneous preference for lipid-rich foods. Surprisingly, the multifunctional membrane-associated protein CD36 appears to play a significant role in this system in rodents. Recently, another plausible gustatory lipid sensor, the GPR120, was also identified in mice, revealing that the mechanism involved in oral fat detection is more complex than initially expected. Interestingly, lingual CD36 and GPR120 displa…

CD36 Displays Features of a Lipid-Sensor Involved in Chylomicron Processing in the Rodent Small Intestine

International audience; The membrane glycoprotein CD36 binds nanomolar concentrations of long-chain fatty acids (LCFA) and is highly expressed on the luminal surface of enterocytes. CD36 deficiency reduces chylomicron production through unknown mechanisms.In this report, we provide novel insights into the potential underlying mechanisms. Our in vivo data demonstrated that CD36 gene deletion in mice did not affect LCFA uptake and their subsequent esterification into triglycerides by the intestinal mucosa at micellar LCFA concentrations prevailing in the intestine. In rodents, CD36 protein early disappeared from the luminal side of intestinal villi during the post-prandial period but only whe…

Link between Intestinal CD36 Ligand Binding and Satiety Induced by a High Protein Diet in Mice

International audience; CD36 is a ubiquitous membrane glycoprotein that binds long-chain fatty acids. The presence of a functional CD36 is required for the induction of satiety by a lipid load and its role as a lipid receptor driving cellular signal has recently been demonstrated. Our project aimed to further explore the role of intestinal CD36 in the regulation of food intake. Duodenal infusions of vehicle or sulfo-N-succinimidyl-oleate (SSO) was performed prior to acute infusions of saline or Intralipid (IL) in mice. Infusion of minute quantities of IL induced a decrease in food intake (FI) compared to saline. Infusion of SSO had the same effect but no additive inhibitory effect was obser…

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…

Peroxisome Proliferator-Activated Receptor Deficiency Increases the Risk of Maternal Abortion and Neonatal Mortality in Murine Pregnancy with or without Diabetes Mellitus: Modulation of T Cell Differentiation

We assessed the implication of peroxisome proliferator-activated receptor (PPAR) alpha deficiency in pregnancy outcome and neonatal survival and in the modulation of T cell differentiation in murine diabetic pregnancy and their offspring. Pregnant wild-type (WT) and PPAR alpha-null mice of C57BL/6J genetic background were rendered diabetic by five low doses of streptozotocin. We observed that, in the absence of diabetes, PPAR alpha deficiency resulted in an increase in abortion rate, i.e. 0% in WT mice vs. 20% in PPAR alpha-null mice [odds ratio (OR) = 14.33; P = 0.013]. Under diabetic conditions, the abortion rate was enhanced, i.e. 8.3% in WT mice vs. 50% in PPAR alpha-null mice (OR = 4.2…

L’intestin, carrefour des régulations du métabolisme lipidique

Sterol Regulatory Element-binding Protein-1c Is Responsible for Cholesterol Regulation of Ileal Bile Acid-binding Protein Gene in Vivo

Ileal bile acid-binding protein (I-BABP) is a cytosolic protein that binds bile acid (BA) specifically. In the ileum, it is thought to be implied in their enterohepatic circulation. Because the fecal excretion of BA represents the main physiological way of elimination for cholesterol (CS), the I-BABP gene could have a major function in CS homeostasis. Therefore, the I-BABP gene expression might be controlled by CS. I-BABP mRNA levels were significatively increased when the human enterocyte-like CaCo-2 cells were CS-deprived and repressed when CS were added to the medium. A highly conserved sterol regularory element-like sequence (SRE) and a putative GC box were found in human I-BABP gene pr…

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.

Obesity interferes with the oro-sensory detection of long-chain fatty acids in Human

International audience

O04 Le sensing intestinal des lipides alimentaires médié par CD36 est-il altéré en cas de syndrome métabolique ?

International audience; [Pas de résumé]

Mécanisme d’absorption intestinale des acides gras à longue chaîne : rôle émergent du CD36

International audience; Excessive lipid intake, associated with a qualitative imbalance, favors the development of obesity and associated diseases. Among the organs involved in lipid homeostasis, the small intestine remains the most poorly known although it is responsible for the lipid bioavailability and largely contributes to the regulation of postprandial hypertriglyceridemia. The mechanism of long chain fatty acid (LCFA) intestinal absorption is not totally elucidated. The synthesis of recent literature indicates that the intestine is able to adapt its absorption capacity to the fat content of the diet. This adaptation takes place through a fat-coordinated induction of LBP and apolipopr…

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…

Deregulated Lipid Sensing by Intestinal CD36 in Diet-Induced Hyperinsulinemic Obese Mouse Model

International audience; The metabolic syndrome (MetS) greatly increases risk of cardiovascular disease and diabetes and is generally associated with abnormally elevated postprandial triglyceride levels. We evaluated intestinal synthesis of triglyceride-rich lipoproteins (TRL) in a mouse model of the MetS obtained by feeding a palm oil-rich high fat diet (HFD). By contrast to control mice, MetS mice secreted two populations of TRL. If the smaller size population represented 44% of total particles in the beginning of intestinal lipid absorption in MetS mice, it accounted for only 17% after 4 h due to the secretion of larger size TRL. The MetS mice displayed accentuated postprandial hypertrigl…

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 [(…

Oro-sensory perception of dietary lipids: new insights into the fat taste transduction.

The sense of taste informs the organism about the quality of ingested food. Five basic taste modalities, e.g., sweet, sour, bitter, salty and umami have so far been identified. Recent compelling evidence from rodent and human studies raise the possibility for an additional sixth taste modality devoted to the perception of lipids. Recent studies strongly suggest that lingual CD36, being implicated in the perception of dietary fat, may act as a gustatory lipid sensor. Knocking down of CD36 gene decreases the spontaneous preference for long chain fatty acids (LCFA) in mice subjected to a free choice situation. Lingual CD36, after activation by LCFA, is able to trigger specific signalling mecha…

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…

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 …

STIM1, CD36 lingual et perception gustative lipidique

> Selon l’Organisation mondiale de la sante (OMS) [1], l’obesite atteint des proportions epidemiques dans le monde, avec plus de 1,6 milliards d’adultes en surpoids et au moins 500 millions de personnes cliniquement obeses. Globalement, un adulte sur dix est obese dans le monde. Cette situation a des consequences importantes en termes de sante publique. En effet, l’obesite, particulierement l’obesite viscerale, est un facteur de risque de pathologies telles que le diabete de type II, les atteintes cardiovasculaires, l’hypertension et certaines formes de cancers [2]. Bien qu’il existe un determinisme genetique, les facteurs environnementaux dont l’alimentation jouent un role important dans l…

Cell mechanisms of gustatory lipids perception and modulation of the dietary fat preference.

Dietary lipids are usually responsible of several metabolic disorders. Recent compelling evidences suggest that there is a sixth taste modality, destined for the detection of oro-gustatory fats. The lipid-binding glycoprotein CD36, expressed by circumvallate papillae (CVP) of the mouse tongue, has been shown to be implicated in oro-gustatory perception of dietary lipids. We demonstrate that linoleic acid (LA) by activating sPLA2, cPLA2 and iPLA2 via CD36, produced arachidonic acid (AA) and lyso-phosphatidylcholine (Lyso-PC) which triggered Ca(2+) influx in CD36-positive taste bud cells (TBC), purified from mouse CVP. LA induced the production of Ca(2+) influx factor (CIF). CIF, AA and Lyso-…

9-cis-Retinoic acid enhances fatty acid-induced expression of the liver fatty acid-binding protein gene

The role of retinoic acids (RA) on liver fatty acid- binding protein (L-FABP) expression was investigated in the well differentiated FAO rat hepatoma cell line. 9-cis-Retinoic acid (9-ci's-RA) specifically enhanced L-FABP mRNA levels in a time- and dose-dependent manner. The higher induction was found 6 h after addition of 10 -6 M 9-CK-RA in the medium. RA also enhanced further both L-FABP mRNA levels and cytosolic L-FABP protein content induced by oleic acid. The retinoid X receptor (RXR) and the peroxisome proliferator-activated receptor (PPAR), which are known to be activated, respectively, by 9-c/s-RA and long chain fatty acid (LCFA), co-operated to bind specifically the peroxisome prol…

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

Ca2+ signaling in taste bud cells and spontaneous preference for fat: Unresolved roles of CD36 and GPR120

Recent compelling evidences from rodent and human studies raise the possibility for an additional sixth taste modality devoted to oro-gustatory perception of dietary lipids. Understanding the mechanisms underlying oro-gustatory detection of dietary fat is critical for the prevention and treatment of obesity. A number of studies have suggested that lingual CD36, a glycoprotein, highly expressed by circumvallate papillae of the tongue, is implicated in the perception of dietary fat taste. G protein-coupled receptors (GPCRs) are important signaling molecules for many aspects of cellular functions. It has been shown that these receptors, particularly GPR120, are also involved in lipid taste per…

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.

6th European Conference on Symbolic and Quantitative Approaches to Reasoning with Uncertainty

International audience; no abstract

Linoleic acid induces calcium signaling, Src kinase phosphorylation, and neurotransmitter release in mouse CD36-positive gustatory cells.

We have recently demonstrated that the cells expressing CD36, localized apically on the taste buds of mouse lingual circumvallate papillae, act as gustatory cells. In the present study we isolated these CD36-positive cells from mouse circumvallate papillae and investigated intracellular signaling events, triggered by a long-chain polyunsaturated fatty acid, i.e. linoleic acid (LA). LA induced increases in free intracellular calcium concentrations, [Ca(2+)](i), by recruiting calcium from endoplasmic reticulum pool via inositol 1,4,5-triphosphate production followed by calcium influx via opening of store-operated calcium (SOC) channels. LA also induced phosphorylation of Src-protein-tyrosine …

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…

Intestinal Fat Absorption: Roles of Intracellular Lipid-Binding Proteins and Peroxisome Proliferator-Activated Receptors

Transcriptional induction of the fatty acid binding protein gene in mouse liver by bezafibrate

AbstractThe mechanism by which hypolipidemic peroxisome proliferators of the fibrate family induce the liver fatty acid binding protein in liver of rodents is unknown. In order to delineate the level at which this protein is induced, the transcriptional activity of the specific gene encoding for liver fatty acid binding protein was measured in isolated hepatocyte nuclei obtained from male Swiss mice daily force-fed during 7 days with 400 mg/kg body weight bezafibrate. This treatment induced a 4-fold increase in the liver fatty acid binding protein transcription rate. Liver fatty acid binding protein mRNA level, measured by Northern blot analysis and cytosolic content of this protein, analyz…

Lipopolysaccharides-mediated increase in glucose-stimulated insulin secretion: involvement of the GLP-1 pathway.

Lipopolysaccharides (LPS) of the cell wall of gram–negative bacteria trigger inflammation, which is associated with marked changes in glucose metabolism. Hyperglycemia is frequently observed during bacterial infection and it is a marker of a poor clinical outcome in critically ill patients. The aim of the current study was to investigate the effect of an acute injection or continuous infusion of LPS on experimentally induced hyperglycemia in wild-type and genetically engineered mice. The acute injection of a single dose of LPS produced an increase in glucose disposal and glucose-stimulated insulin secretion (GSIS). Continuous infusion of LPS through mini-osmotic pumps was also associated wi…

Sensing of lipids via receptor signalling in taste buds

Intestinal CD36. A lipid-sensor involved in the processing of chylomicrons in rodents

International audience; CD36 is a multifunctional glycoprotein which binds nanomolar concentrations of long-chain fatty acids (LCFA) and is highly expressed on the luminal surface of enterocytes. Despite of its implication in oleoylethanolamide (OEA) and chylomicron synthesis, CD36 function in small intestine remains incompletely understood. Our in vivo data demonstrated that CD36 gene deletion in mice did not affect intestinal LCFA uptake. CD36 protein disappeared early from the luminal side of intestinal villi during the post-prandial period but only when the diet contained lipids. This drop was significant 1 h after a lipid supply and was associated with ubiquitination of CD36. Using CHO…

Effet anti-obésité des CLA : mythe ou réalité ?

Conjugated linoleic acids (CLA) are positional and geometric isomers of linoleic acid. Inclusion of CLA in the diet provokes a rapid and marked decrease in body weight gain and adiposity in mice leading to a lipoatrophic syndrome. However, CLA supplementation raised fasting blood glucose and insulin concentrations and was associated with severe insulin resistance and liversteatosis. Conflicting results have been reported with regard to reduction of fat mass in humans. We have reviewed the publish literature regarding the effect of CLA on body composition in humans and animal models. These studies indicate that t10-c12 was the isomer that reduced adipose fat storage, however it also increase…

Do we taste fat?

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. However, the inborn attraction of mammals for fatty foods raises the possibility of an additional oro-sensory modality devoted to fat perception. During a long time, dietary lipids were thought to be detected only by trigeminal (texture perception), retronasal olfactory, and post-ingestive cues. This minireview analyses recent findings showing that the gustation also plays a significant role in dietary lipid perception.

Lack of association of cd36 snps with early onset obesity : A meta-analysis in 9,973 european subjects

A recent study suggested that four CD36 polymorphisms (namely rs3211867, rs3211883, rs3211908, and rs1527483) were associated with an increased risk of obesity, an increased BMI and percentage of body fat in European adolescents. We first attempted to confirm these results in three independent case-control genome-wide association studies (GWAS) data totaling 3,509 subjects of French and German origin, but we were unable to find any association of these variants with early onset obesity risk. We then genotyped the four CD36 single-nucleotide polymorphisms (SNPs) in a large population-based study of 4,667 Finnish subjects and we did not replicate any of the recently reported associations with…

Obesogen effects after perinatal exposure of 4,4′-sulfonyldiphenol (Bisphenol S) in C57BL/6 mice

International audience; Bisphenol A were removed from consumer products and replaced by chemical substitutes such as Bisphenol S (BPS). Based on their structural similarity, BPS may be obesogen like Bisphenol A in mice. Our objective was to determine the impact of BPS on lipid homeostasis in C57B1/6 mice after perinatal and chronic exposure. Pregnant mice were exposed to BPS via the drinking water (0.2; 1.5; 50 mu g/kg bw/d). Treatment began at gestational day 0 and continued in offspring up to 23-weeks old. Then, offspring mice were fed with a standard or high fat diet. The body weight, food consumption, fat mass and energy expenditure were measured. A lipid load test was performed to chec…

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

Cet article ne possède pas de résumé.

From fatty-acid sensing to chylomicron synthesis: Role of intestinal lipid-binding proteins

International audience; Today, it is well established that the development of obesity and associated diseases results, in part, from excessive lipid intake associated with a qualitative imbalance. Among the organs involved in lipid homeostasis, the small intestine is the least studied even though it determines lipid bioavailability and largely contributes to the regulation of postprandial hyperlipemia (triacylglycerols (TG) and free fatty acids (FFA)). Several Lipid-Binding Proteins (LBP) are expressed in the small intestine. Their supposed intestinal functions were initially based on what was reported in other tissues, and took no account of the physiological specificity of the small intes…

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 …

A New Method for Studying Licking Behavior Determinants in Rodents: Application to Diet-Induced Obese Mice

OBJECTIVE An original device for exploring taste-guided reward behavior in rodents using a newly designed computer-controlled liquid delivery system equipped with "lickometers" is described. METHODS This octagonal shaped "gustometer" is composed of eight shutters that give random access during a few seconds to eight bottles delivering different liquid stimuli. This original design, which forces the animal to move for access to the drinking source, allows a simultaneous analysis of the licking behavior and motivation to drink. Determination of the sucrose licking behavior in diet-induced obese mice was used to validate this method because nutritional obesity disturbs the sweet taste percepti…

ROLE OF THE CHORDA TYMPANI AND GLOSSOPHARYNGEAL NERVES IN ORAL LINOLEIC ACID DETECTION IN MICE

Luminal Lipid Regulates CD36 Levels and Downstream Signaling to Stimulate Chylomicron Synthesis

International audience; The membrane glycoprotein CD36 binds nanomolar concentrations of long chain fatty acids (LCFA) and is highly expressed on the luminal surface of enterocytes. CD36 deficiency reduces chylomicron production through unknown mechanisms. In this report, we provide novel insights into some of the underlying mechanisms. Our in vivo data demonstrate that CD36 gene deletion in mice does not affect LCFA uptake and subsequent esterification into triglycerides by the intestinal mucosa exposed to the micellar LCFA concentrations prevailing in the intestine. In rodents, the CD36 protein disappears early from the luminal side of intestinal villi during the postprandial period, but …

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