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PDF is a draft version; International audience; We present a logical framework allowing us to express assessment offacts (is it proven?) and arguments (is it sound?) together with a proofsystem to answer these questions. Our motivation is to clarify the notion of validity in the context of logic-based arguments along different aspects (such as the formulas used and the inference scheme). Origi-nality lies in the possibility for the user to design their own arguments chemes. We show that classical inference obtains when arguments arebased on classical schemes (e.g. Hilbert axioms). We go beyond clas-sical logic by distinguishing “proven” formulas from “uncontroversial”ones (whose negation is not proven). Hence a formal definition of a fallacious argument: it uses controversial formulas or schemes recognizedas illicit. We express some rational arguments and fallacies in the formof schemes.

International audience; Orosensory perception of sweet stimulus is blunted in diet-induced obese (DIO) rodents. Although this alteration might contribute to unhealthy food choices, its origin remains to be understood. Cumulative evidence indicates that prebiotic manipulations of the gut microbiota are associated with changes in food intake by modulating hedonic and motivational drive for food reward. In the present study, we explore whether a prebiotic supplementation can also restore the taste sensation in DIO mice. The preference and licking behavior in response to various sucrose concentrations were determined using respectively two-bottle choice tests and gustometer analysis in lean and obese mice supplemented or not with 10% inulin-type fructans prebiotic (P) in a preventive manner. In DIO mice, P addition reduced the fat mass gain and energy intake, limited the gut dysbiosis and partially improved the sweet taste perception (rise both of sucrose preference and number of licks/10 s vs. non-supplemented DIO mice). No clear effect on orosensory perception of sucrose was found in the supplemented control mice. Therefore, a preventive P supplementation can partially correct the loss of sweet taste sensitivity found in DIO mice, with the efficiency of treatment being dependent from the nutritional status of mice (high fat diet vs. regular chow).

Some obese subjects overeat lipid-rich foods. The origin of this eating behavior is unknown. We have here tested the hypothesis that these subjects could be characterized by an impaired fatty taste sensitivity linked to a change in the gustatory papillae microbial and salivary environment. The composition of microbiota and saliva surrounding the circumvallate papillae was analyzed in combination with the orosensory lipid detection threshold in normal weight (NW) and obese (O) adults. Microbial architecture was similar to what was known in feces, but with an increased frequency of Proteobacteria. No difference in the orosensory sensitivity to lipids and composition of oral microbiota and saliva was observed between NW and O subjects. By contrast, specific bacterial and salivary signatures were found in lipid non-tasters, irrespectively of BMI. A multivariate approach highlighted that the salivary flow, lysozyme activity, total antioxidant capacity and TM7 bacterial family discriminated between tasters and non-tasters. Subgroup analysis of obese tasters (OT) versus obese non-tasters (ONT) identified specific bacterial metabolic pathways (i.e. phosphotransferase and simple sugar transport systems) as being higher in ONT. Altogether with the identification of a set of significant salivary variables, our study suggests that an “obese tongue” phenotype is associated with decreased orosensory sensitivity to lipids in some obese subjects.

IF (4.042); International audience; ObjectiveAn original device for exploring taste‐guided reward behavior in rodents using a newly designed computer‐controlled liquid delivery system equipped with “lickometers” is described.MethodsThis 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 perception in rodents.ResultsA rise in sucrose response threshold and a decrease in the motivation to drink sweet solutions were found in mice fed the obesogenic diet. These data were highly reproducible among independent studies and corroborated the existence of functional links between diet‐induced obesity and gustation in rodents.ConclusionsThe FRM‐8 gustometer appears to be especially suitable for exploring determinants of behavioral outputs in response to oro‐sensory stimuli in the mouse. It also provides substantial information on the taste‐reward relationship, useful for better understanding the origin of gustatory efficiency or, conversely, dysfunction, as reported in nutritional obesity.

IF 5.088; International audience; Obesity is undoubtedly one of the major public health challenges worldwide because of its rapid progression and deleterious effects of associated diseases. The easier access to tasty and energy-dense foods is thought to greatly contribute to this epidemic. Studies also report that obese subjects and animals (rats and mice) preferentially consume foods rich in fat when they can choose. The origin of this eating behavior remains elusive. Over the last decade, the existence of a taste of fat, besides textural and olfactory cues, was supported by a growing number of studies. The existence of a sixth taste modality devoted to the detection/perception of dietary lipids might offer additive information on the quality of food. While the sense of taste is recognized to be a driving-force guiding food choice, interest in the putative relationships between lipids, gustation and obesity is only now emerging. This mini-review will attempt to summarize our current knowledge on this new field of research.

International audience; The literature on inconsistency measures has ignored a distinction, that is, differentiating absolute measures and relative measures. An absolute measure gives the total amount of inconsistency in the knowledge base but a relative measure computes, by some criteria, the proportion of the base that is inconsistent. To compare the inconsistency measures, researchers have proposed postulates for such measures. We split these postulates into three groups: ones (including two new postulates) that relative measures should satisfy, ones inappropriate for relative measures, and ones that relative measures may satisfy. We obtain some new results upon the relationships between these groups of postulates. On these grounds, we introduce a formal definition for relative inconsistency measures. We consider some relative measures previously proposed and define several new ones that serve as examples. We show that all of these measures satisfy the new formal definition.

Origin of the great inter-individual variability of the fatty taste perception found in obese subjects is challenging. The fact that recent studies suggest interrelations between taste perception and oral microbiota composition, prompt us to explore the putative impact of such a connection in the context of obesity. To check this hypothesis, the oro-sensory perception thresholds of linoleic acid and the composition of oral microbiota surrounding the gustatory circumvallate papillae (CVPs) were analyzed in obese adult men (BMI ≥ 30 kg/m2, n = 42). A specific microbial signature (higher diversity, pro-inflammatory bacterial profile, lower methanogenesis activity) discriminated subjects with a degraded fatty taste sensitivity (perception threshold ≥ 0.05% LA = Low-LA tasters, n = 22) from high-LA tasters (n = 20). Collectively, these data substantiate the association between the microbial microenvironment surrounding CVPs and the fatty taste sensitivity and provide a plausible explanation about the variability of the fatty taste sensitivity in obesity.

Rule learning is a data analysis task consisting of extracting rules to generalize examples. For a data scientist, some generalizations called here admissible generalizations, make more sense. We explore formal properties of admissible generalizations. A formalization for generalization of examples is proposed that allows to express rule admissibility. Some admissible generalizations are captured by topological operators. We examine selecting supersets of examples that induce these operators and we define classes of such choice functions. This formalization is particularly developed in the case of numerical attributes. Classes of such functions are associated with notions of generalization and they are used to comment some behaviours of the CN2 algorithm.

Author Correction: obese subjects with specifc gustatory papillae microbiota and salivary cues display an impairment to sense lipids Correction to: Scientifc Reports https://doi.org/10.1038/s41598-018-24619-1, published online 30 April 2018; International audience; A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

International audience; Ranking-based semantics are a way of assessing the acceptability of arguments in an abstract argumentation framework, by providing a ranking on arguments. This paper aims at going towards a generalization of the construction of such semantics, by investigating subsumption and incompatibility cases that may arise when principles that may enter into their composition are combined.

Resume Discipline Experimental/mecanismes cellulaires et moleculaires. Introduction et but de l’etude La surconsommation d’aliments riches en sucres et en graisses est un des facteurs de risque d’obesite. Ces aliments s’averent fortement attractifs probablement en raison de la satisfaction hedonique qu’ils procurent. Ce constat suppose l’existence d’une detection precoce et selective de ces nutriments des la mise en bouche des aliments orientant les choix alimentaires. Chez le rat, le fait que des animaux rendus obeses par regime surconsomment les aliments denses en energie suggere que leur detection oro-sensorielle des sucres et lipides pourrait etre perturbee. Ce phenomene est reversible puisque des rats initialement obeses ayant subi un by-pass gastrique Roux en Y delaissent les aliments riches en sucres et graisses au profit d’un regime pauvre en energie. Les mecanismes a l’origine de ces modifications comportementales sont actuellement mal connus. Pour tenter de les elucider, nous avons transpose chez la souris deux chirurgies bariatriques largement pratiquees chez l’Homme : la sleeve gastrectomie (SG, chirurgie restrictive) et le by-pass gastrique Roux en Y (RYGBm) connues pour impacter les choix alimentaires. Utilisant ces modeles, nous avons tente de repondre a la question suivante : Quelle est l’evolution de la detection oro-sensorielle d’un sucre (le saccharose) chez des souris obeses ayant subies une SG ou un RYGBm ? Materiel et methodes Cette etude a ete validee par les comites ethiques ad hoc. Pour chaque modele de chirurgie, 3 groupes de souris ont ete constitues : des temoins operes a blanc en regime standard (T-Std) ou rendus obeses par regime gras (T-HFD) et des souris obeses operees (SG ou RYGBm) maintenues en regime HFD apres operation pour cibler uniquement l’impact de la chirurgie. La composition corporelle (RMN quantitative) et l’intolerance au glucose (OGTT) ont ete evaluees avant et apres chirurgie. La sensibilite orosensorielle du sucre a ete analysee au moyen d’un gustometre permettant l’analyse de la reponse (lapees) des animaux a differentes concentrations de saccharose. Resultats et analyse statistique La SG et le RYGBm induisent une diminution significative de la masse grasse et ameliorent la sensibilite au glucose des souris initialement obeses en depit du fait qu’elles soient maintenues en regime HFD. Globalement, la chute du nombre total de lapees par session de 30 min, du nombre de lapees/10 sec en fonction de la concentration de saccharose et du seuil de detection oro-sensoriel du saccharose observe chez les T-HFD vs T-Std est partiellement corrigee par les 2 chirurgies, le RYGBm s’averant plus efficace que la SG. Conclusion Ces donnees montrent que la chirurgie bariatrique ameliore significativement la perception oro-sensorielle du sucre chez la souris initialement obese en depit de son maintien sur un regime obesogene. Cette observation, inedite pour cette espece, ouvre de nouvelles perspectives d’etude du changement du comportement alimentaire au cours de l’obesite.

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 orale des lipides mais se traduit egalement par une preference accrue pour le « gras », plaide en faveur de cette these. Chez l’homme, nos travaux indiquent que les sujets obeses, dont la detection oro-sensorielle des lipides est defectueuse, surconsomment des aliments riches en graisse. Ces donnees murines et humaines suscitent une question fondamentale : quel est le lien entre lipides, obesite et desordres gustatifs ? Cette mini-revue se propose de faire le point des connaissances actuelles sur ce sujet.

La Presse Medicale - In Press.Proof corrected by the author Available online since mardi 16 aout 2016

The upsurge in studies of Emile Durkheim may surprise and even irritate those who see a break from the "founding fathers" as essential for the progress of sociology. This chapter shows that anomie suicide is situated very precisely at the turning-point of the work, in other words at the moment when the theory of the "juste milieu" is on the point of being supplanted by the theory of equilibrium and reference to variables by reference to trends. This strange and contradictory attitude of Durkheim towards the suicide of women is not of solely anecdotal interest. In terms of taking account of the lesser frequency of suicide among women, the possibility of an explanation of a biological or "organic" type is furthermore explicitly rejected: This influence of gender is much more an effect of social causes than of organic causes.

IF 3.112; International audience; Understanding the mechanisms governing food intake is a public health issue given the dramatic rise of obesity over the world. The overconsumption of tasty energy-dense foods rich in lipids is considered to be one of the nutritional causes of this epidemic. Over the last decade, the identification of fatty acid receptors in strategic places in the body (i.e. oro-intestinal tract and brain) has provided a major progress in the deciphering of regulatory networks involved in the control of dietary intake. Among these lipid sensors, CD36/SR-B2 appears to play a significant role since this membrane protein, known to bind long-chain fatty acid with a high affinity, was specifically found both in enterocytes and in a subset of taste bud cells and entero-endocrine cells. After a short overview on CD36/SR-B2 structure, function and regulation, this mini-review proposes to analyze the key findings about the role of CD36/SR-B2 along of the tongue-gut axis in relation to appetite control. In addition, we discuss whether obesogenic diets might impair lipid sensing mediated by CD36/SR-B2 along this axis.

Postulates for inconsistency measures are examined, the set of postulates proposed by Hunter and Konieczny being the starting point. The focus is on two postulates that were questioned by various authors. Studying the first suggests a systematic transformation to guard postulates against a certain kind of counter-examples. The second postulate under investigation here is devoted to independence, for which a general version is proposed that avoids the pitfalls mentioned in the literature. Combining these two additions with some postulates previously introduced by the same author, a set of basic postulates alternative to the core set given by Hunter and Konieczny arises.

International audience; This paper investigates when two abstract logic-based argumentation systems are equivalent. It defines various equivalence criteria, investigates the links between them, and identifies cases where two systems are equivalent with respect to each of the proposed criteria. In particular, it shows that under some reasonable conditions on the logic underlying an argumentation system, the latter has an equivalent finite subsystem, called core. This core constitutes a threshold under which arguments of the system have not yet attained their final status and consequently adding a new argument may result in status change. From that threshold, the statuses of all arguments become stable.

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 [(TG)pl] concentrations was analyzed in overnight-fasted lean and obese individuals subjected to a whole-mouth stimulation (sipand-spit procedure) with a control or 1% LA emulsions for 5 min according to a within-subject randomized design. Results: A large distribution of LA detection was shown in both groups. Mean detection thresholds were 0.053% (wt:wt) and 0.071% (wt:wt) in lean and obese subjects, respectively. No relation between the LA detection threshold and BMI was observed. The 5 subjects who detected only the higher concentration of LA (5% wt: wt) or were unable to distinguish properly between control and LA emulsions were obese. An analysis of dietary habits showed that these obese LA nontasters consumed more lipids and energy than did all other subjects. Brief whole-mouth stimulations (sip-and-spit procedure) with a control or 1% LA emulsion revealed an LAmediated rise in (TG)pl concentrations in overnight-fasted, lean subjects. The origin of this change seemed to be hepatic. This (TG)pl upregulation was not shown in obese subjects, which suggested that obesity led to disturbances in the oral-brainstem-periphery loop. Conclusion: Altogether, these data strongly suggest that obesity may interfere with the orosensory system responsible for the detection of free long-chain fatty acids in humans. This trial was registered at clinicaltrials.gov as NCT02028975. Am J Clin Nutr doi: 10. 3945/ajcn.113.077198.

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 perception. We have shown that dietary long-chain fatty acids (LCFAs), in CD36-positive taste bud cells (TBC), induce increases in free intracellular Ca(2+) concentrations, [Ca(2+)]i, by recruiting Ca(2+) from endoplasmic reticulum (ER) pool via inositol 1,4,5-triphosphate production, followed by Ca(2+) influx via opening of store-operated Ca(2+) (SOC) channels. GPR120 is also coupled to increases in [Ca(2+)]i by dietary fatty acids. We observed that stromal interaction molecule 1 (STIM1), a sensor of Ca(2+) depletion in the ER, mediated fatty acid-induced Ca(2+) signaling and spontaneous preference for fat in the mouse. In this review article, we discuss the recent advances and unresolved roles of CD36 and GPR120 in lipid taste signaling in taste bud cells.

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.

Discipline Clinique. Introduction et but de l’etude L’augmentation de la prevalence de l’obesite est l’un des defis majeurs de sante publique. En cas d’obesite morbide, la chirurgie bariatrique, qu’elle soit restrictive (Sleeve gastrectomie - SG) ou malabsorptive (court-circuit gastrique - CCG), entraine une reduction a long terme du poids et des co-morbitites. Ces interventions s’accompagnent generalement d’un changement comportemental privilegiant les aliments peu palatables pauvres en sucres et en graisses. Cette observation suscite deux questions complementaires : la chirurgie bariatrique affecte-t-elle la detection oro-sensorielle du sucre et du gras ? Quel est l’impact respectif de la SG et de la CCG sur ce parametre ? Materiel et methodes L’inclusion des patients a ete realisee apres consentement eclaire et validation du comite de protection des personnes. Les seuils de detection du saccharose (S) puis de l’acide linoleique (AL) ont ete etudies au moyen de tests triangulaires (3 alternative-forced choice) chez des femmes adultes souffrant d’une obesite severe (IMC > 43 kg/m2) 2 semaines avant SG (n = 32) ou CCG (n = 13) puis 6 mois apres la chirurgie. Huit et 18 concentrations croissantes de S et de AL ont ete respectivement testees le matin chez les sujets a jeun ayant consommes la veille au soir un repas standardise. Les solutions temoins etaient de l’eau de Volvic seule (S) ou texturee avec 5 % de gomme d’acacia, 5 % d’huile de paraffine et 0,01 % d’EDTA (AL). Resultats et analyse statistique La perte moyenne de poids a 6 mois post-chirurgie etait respectivement de 31 % (SG) et 36,5 % (CCG). Pour le sucre, le seuil de detection du S etait similaire avant et 6 mois apres chirurgie quelle que soit la technique utilisee (SG : 0,54 % vs 0,56 %, p = 0,44 ; CCG : 0,65 % vs 0,51 %, p = 0,09, test Wilcoxon-Pratt), meme si une tendance a la baisse etait observable apres CCG. Aucun changement significatif du seuil de detection de l’AL apres SG (0,64 mM vs 0,50 mM, p= 0,46) n’a ete observe. En revanche, la CCG a provoque une diminution significative du seuil de detection lipidique (0,90 mM vs 0,41 mM, p = 0,01). Conclusion SG et la CCG ne semblent pas affecter la detection oro-sensorielle du sucre contrairement au « gras » dont la sensibilite semble amelioree apres CCG (i.e. detection a partir d’une plus faible concentration). Ces resultats inedits indiquent que SG et CCG n’ont pas le meme impact sur la detection du sucre et du gras. Ils montrent egalement que la sensibilite de ces 2 modalites gustatives peut etre regulee de facon independante l’une de l’autre. Ces observations sont paradoxalement discordantes avec le ressenti des patientes qui decrivent une augmentation de l’intensite des gouts « gras » et sucre dans plus de 2/3 des cas apres intervention quel que soit le type de chirurgie. Le changement des choix alimentaires consecutifs a la chirurgie bariatrique est donc un phenomene complexe ne se limitant pas a la sensibilite gustative.

International audience; Dung’s (1995) argumentation framework takes as input two abstract entities: a set of arguments and a binary relation encoding attacks between these arguments. It returns acceptable sets of arguments, called extensions, w.r.t. a given semantics. While the abstract nature of this setting is seen as a great advantage, it induces a big gap with the application that it is used to. This raises some questions about the compatibility of the setting with a logical formalism (i.e., whether it is possible to instantiate it properly from a logical knowledge base), and about the significance of the various semantics in the application context. In this paper we tackle the above questions. We first propose to fill in the previous gap by extending Dung’s (1995) framework. The idea is to consider all the ingredients involved in an argumentation process. We start with the notion of an abstract monotonic logic which consists of a language (defining the formulas) and a consequence operator. We show how to build, in a systematic way, arguments from a knowledge base formalised in such a logic. We then recall some basic postulates that any instantiation should satisfy. We study how to choose an attack relation so that the instantiation satisfies the postulates. We show that symmetric attack relations are generally not suitable. However, we identify at least one ‘appropriate’ attack relation. Next, we investigate under stable, semi-stable, preferred, grounded and ideal semantics the outputs of logic-based instantiations that satisfy the postulates. For each semantics, we delimit the number of extensions an argumentation system may have, characterise the extensions in terms of subsets of the knowledge base, and finally characterise the set of conclusions that are drawn from the knowledge base. The study reveals that stable, semi-stable and preferred semantics either lead to counter-intuitive results or provide no added value w.r.t. naive semantics. Besides, naive semantics either leads to arbitrary results or generalises the coherence-based approach initially developed by Rescher and Manor (1970). Ideal and grounded semantics either coincide and generalise the free consequence relation developed by Benferhat, Dubois, and Prade (1997), or return arbitrary results. Consequently, Dung’s (1995) framework seems problematic when applied over deductive logical formalisms.

International audience; This paper is concerned with intelligent agents that are able to perform nonmonotonic reasoning, not only with, but also about general rules with exceptions. More precisely, the focus is on enriching a knowledge base K with a general rule that is subsumed by other rules already there. Such a problem is important because evolving knowledge needs not follow logic as it is well-known from e.g. the belief revision paradigm. However, belief revision is mainly concerned with the case that the extra information logically conflicts with K. Otherwise, the extra knowledge is simply doomed to extend K with no change altogether. The problem here is different and may require a change in K even though no inconsistency arises.The idea is that when a rule is to be added, it might need to override any rule that subsumes it: preemption must take place. A formalism dedicated to reasoning with and about rules with exceptions is introduced. An approach to dealing with preemption over such rules is then developed. Interestingly, it leads us to introduce several implicants concepts for rules that are possibly defeasible.

International audience; Human exposure to BPA is low but it occurs during the lifetime and gestation appears to be a critical exposure windows. BPA is an endocrine disruptor which could induce alteration in energy metabolism and obesity development. Pregnant mice were exposed to BPA (0.2, 20 and 2000 μg/kg bw per day) and offsprings were fed with a high fat diet (HFD). Energy expenditure, fat mass and lean masses were measured. A lipid load test was performed in order to determine a potential disturbance of intestine lipid metabolism. BPA induced a effect gender- and dose-dependent effect (non monotonic effect). Only BPA-exposed male offspring exhibited a higher overweight (in correlation with fat mass) than control. A decrease of energy expenditure, a post-prandial hypotriglyceridemia and liver steatosis were observed. BPA appears to potentiate HFD-induced obesity and to alter lipid metabolism in adipose tissue, liver and intestine.; L’Homme est faiblement exposé au bisphénol A (BPA) mais un effet cumulatif délétère est probable, notamment lors de la gestation. C’est un perturbateur endocrinien qui pourrait affecter le métabolisme énergétique et la mise en place de l’obésité. Des souris ont été exposées périnatalement au BPA (0,2, 20 et 2000 μg/kg pc par jour) et les petits ont été soumis à un régime hyperlipidique. Le métabolisme énergétique et les masses grasse et maigre ont été suivis. Un test de surcharge lipidique a été réalisé pour déterminer si le métabolisme intestinal des lipides était perturbé. Les résultats montrent un effet du BPA dépendant du sexe et de la dose (non monotonique). Seule la progéniture mâle exposée présentait un surpoids plus important (corrélé avec la masse grasse) par rapport aux témoins. Une baisse de la dépense énergétique, une hypotriglycéridémie post-prandiale et une stéatose hépatique ont été observées. Le BPA semble potentialiser l’obésité induite par un régime hyperlipidique et agir sur le métabolisme lipidique au niveau du tissu adipeux, du foie et de l’intestin.

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, fatty acid–evoked Ca2+ signaling and ERK1/2 phosphorylation were decreased in both human TBCs after small interfering RNA knockdown of CALHM1 channel and in TBCs from Calhm1−/− mice. Targeted knockdown of ERK1/2 by small interfering RNA or PD0325901 (MEK1/2 inhibitor) in the tongue and genetic ablation of Erk1 or Calhm1 genes impaired preference for dietary fat in mice. Lingual inhibition of ERK1/2 in healthy volunteers also decreased orogustatory sensitivity for linoleic acid. Our data demonstrate that ERK1/2-MAPK cascade is regulated by the opening of CALHM1 Ca2+ channel in TBCs to modulate orogustatory detection of dietary lipids in mice and humans.—Subramaniam, S., Ozdener, M. H., Abdoul-Azize, S., Saito, K., Malik, B., Maquart, G., Hashimoto, T., Marambaud, P., Aribi, M., Tordoff, M. G., Besnard, P., Khan, N. A. ERK1/2 activation in human taste bud cells regulates fatty acid signaling and gustatory perception of fat in mice and humans.

La présence de lipides dans les aliments les rend plus crémeux, onctueux et fondants, en bref plus appétants. Ce constat n'est pas anodin. Il indique que les lipides sont aisément perçus dans une matrice alimentaire qui peut être complexe. Jusqu'à une période récente, on pensait que seules la texture et l'odeur des lipides alimentaires étaient responsables de leur détection orosensorielle. Au cours de la dernière décennie, cette vision restrictive a progressivement été remise en cause par une série de données animales et humaines suggérant que la voie gustative pourrait être également impliquée dans ce phénomène. Après un rappel succinct sur le système gustatif, cette mini-revue se propose de faire un point à date sur une question polémique : existe-t-il un goût du gras ?

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 check the postprandial triglyceridemia. Plasma parameters and mRNA gene expression in adipose tissues were also analysed. BPS induced overweight in male mice offspring fed with a HFD at the two highest doses. There was no change in food intake and energy expenditure. The overweight was correlated to the fat mass, hyperinsulinemia and hyperleptinemia. The plasma triglyceride clearance was significantly increased with BPS and tyloxapol (R) (triglyceride clearance inhibitor) reversed this phenomenon. BPS induced alteration in mRNA expression of marker genes involved in adipose tissue homeostasis: hormone sensitive lipase, PPAR gamma, insulin receptor, SOCS3 and adiponectin. This is the first time that BPS is described as obesogenic at low doses and after perinatal and chronic exposure in male mice. BPS potentiated the obesity induced by a HFD by inducing the lipid storage linked to faster lipid plasma clearance. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

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 hypertriglyceridemia up to 3 h due to a defective TRL clearance. These alterations reflected a delay in lipid induction of genes for key proteins of TRL formation (MTP, L-FABP) and blood clearance (ApoC2). These abnormalities associated with blunted lipid sensing by CD36, which is normally required to optimize jejunal formation of large TRL. In MetS mice CD36 was not downregulated by lipid in contrast to control mice. Treatment of controls with the proteosomal inhibitor MG132, which prevented CD36 downregulation, resulted in blunted lipid-induction of MTP, L-FABP and ApoC2 gene expression, as in MetS mice. Absence of CD36 sensing was due to the hyperinsulinemia in MetS mice. Acute insulin treatment of controls before lipid administration abolished CD36 downregulation, lipid-induction of TRL genes and reduced postprandial triglycerides (TG), while streptozotocin-treatment of MetS mice restored lipid-induced CD36 degradation and TG secretion. In vitro, insulin treatment abolished CD36-mediated up-regulation of MTP in Caco-2 cells. In conclusion, HFD treatment impairs TRL formation in early stage of lipid absorption via insulin-mediated inhibition of CD36 lipid sensing. This impairment results in production of smaller TRL that are cleared slowly from the circulation, which might contribute to the reported association of CD36 variants with MetS risk.

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 of a sixth taste modality devoted to the perception of lipids. The main steps leading to this new paradigm (i.e., chemoreception of LCFA in TBC, cell signaling cascade, transfer of lipid signals throughout the gustatory nervous pathway, and their physiological consequences) will be critically analyzed. The limitations to this concept will also be discussed in the light of our current knowledge of the sense of taste. Finally, we will analyze the recent literature on obesity-related dysfunctions in the orosensory detection of lipids ("fatty" taste?), in relation to the overconsumption of fat-rich foods and the associated health risks.

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 study from our laboratory indicates that obese subjects, in which the oro-sensory detection of lipids is defective, over-consume fatty foods. These murine and human data raise a fundamental question: what are the relationships between dietary lipids, obesity and taste disorders? This aim of this mini-review is to explore this issue in the light of our current knowledge.; La gustation est un système dynamique capable d’une adaptation physiologique rapide en réponse aux changements environnementaux permanents qui caractérisent notre alimentation (rythme, qualité, quantité). Basé sur la modulation des seuils de sensibilité gustative, ce système homéostatique contribue à la construction du comportement alimentaire en orientant les choix de consommation. On peut donc penser qu’un dysfonctionnement de ce système régulateur peut avoir un impact sur les habitudes alimentaires et donc, à terme, sur la santé. La mise en évidence récente chez le rongeur (rat, souris) qu’une obésité induite par le régime non seulement entraîne une détérioration de la détection orale des lipides mais se traduit également par une préférence accrue pour le «gras», plaide en faveur de cette thèse. Chez l’homme, nos travaux indiquent que les sujets obèses, dont la détection oro-sensorielle des lipides est défectueuse, surconsomment des aliments riches en graisse. Ces données murines et humaines suscitent une question fondamentale : quel est le lien entre lipides, obésité et désordres gustatifs? Cette mini-revue se propose de faire le point des connaissances actuelles sur ce sujet.

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 apolipoproteins. CD36 could operate as a lipid sensor responsible for a transducing signal related to the lipid content of the diet at the origin of this intestinal adaptation. This lipid-mediated metabolic response may lead to the formation of large chylomicrons rapidly degraded in the blood. All together, these new data indicate that this intestinal lipid sensing mechanism may be a therapeutic target for reducing the postprandial hypertriglyceridemia and associated cardiovascular risks.; L’apport excessif de lipides, associé à un déséquilibre qualitatif, favorise le développement de l’obésité et des maladies associées. Parmi les organes impliqués dans l’homéostasie lipidique, l’intestin est le moins étudié alors qu’il contribue à la biodisponibilité des lipides et à l’hypertriglycéridémie postprandiale. Le mécanisme d’absorption des lipides n’est pas totalement élucidé mais, contrairement à ce qui est établi, l’intestin adapte ses capacités d’absorption en fonction de la quantité de lipides du régime. Cette adaptation s’exerce via la modulation des gènes impliqués dans la formation des chylomicrons, comme les lipid-binding proteins (LBP) et certaines apolipoprotéines. Une LBP membranaire, le CD36 serait un senseur des lipides entérocytaires qui, via la transduction d’un signal intracellulaire, déclencherait l’induction du niveau des protéines optimisant la sécrétion de chylomicrons plus rapidement dégradés au niveau sanguin. Le CD36 constituerait une nouvelle cible permettant de réduire l’hypertriglycéridémie postprandiale, facteur de risque des maladies cardiovasculaires.

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 wall in mammals and even a lipid-like pheromone in insects. Similar function might also exist in the brain in which a CD36-dependent sensing of fatty acids has been reported in ventromedial hypothalamic neurons in rodents. Specific recognition of lipid-related molecules by a receptor-like protein highly conserved throughout the evolution strongly suggests that lipid-sensing by CD36 is responsible for basic physiological functions in relation with behavior, energy balance and innate immunity.

Representing knowledge in a rule-based system takes place by means of "if…then…" statements. These are called production rules for the reason that new information is produced when the rule fires. The logic attached to rule-based systems is taken to be classical inasmuch as "if…then…" is encoded by material implication. However, it appears that the notion of triggering "if…then…" amounts to different logical definitions. The paper investigates the matter, with an emphasis upon consistency because reading "if… then…" statements as rules calls for a notion of rule consistency that does not conform with consistency in the classical sense. Natural deduction is used to explore entailment and equivalence among various formulations and properties.

In human beings, women are at lower risk of cardiovascular diseases, and respond differently from men to dietary fatty acids.The aim of the present study was to investigate (i) the influence of gender on the response of lipid metabolism to dietary n-3 PUFA, and (ii) the contribution of PPARalpha to this response.Male and female mice, wild-type (WT) and PPARalpha-null (KO), were fed on diets rich in either saturated FA (SFA) or 18:3 n-3 (ALA). Lipid composition, mRNA levels and certain activities of key enzymes and major transcription factors were determined in the liver. WT mice were slightly affected by dietary FA. However, in WT female mice, but not in males, mRNA levels of PPARalpha-dependent genes (L-FABP, ACO) were higher in the mice fed on the ALA-rich diet. When compared to WT mice, KO female mice exhibited a decreased lipogenesis capacity (40% lower FAS, ACC, and SREBP-1c mRNA level), whereas KO males showed a decrease in peroxisomal beta-oxidation (activity and expression of ACO reduced by 20 and 40%, respectively). When compared to SFA-fed KO mice, steatosis was twice lower in KO mice fed on ALA, despite the absence of dietary effect on plasma TG, CPT1 and ACO activities, or ACC and FAS expression. Besides, in mice on the SFA diet, steatosis was alleviated in females, and CPT1 expression was up-regulated to a higher extent in females than in males (2.7- and 3.6-fold, respectively, as compared to the corresponding WT groups).Our data suggests estrogen to modulate the regulation of hepatic lipid metabolic pathway by dietary fatty acids. Besides, PPARalpha invalidation resulted in unexpected regulations by ALA of its known targets and was compensated partly in females, which was therefore less sensitive to the detrimental effects of a SFA-rich diet.

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 polyinsatures ω6/ω3 trop eleve) participe, sans nul doute, a l’augmentation de la prevalence de l’obesite et des pathologies associees (atteintes vasculaires, diabete de type II, hypertension, cancers). Cette attirance pour les corps gras n’est pas specifique a l’Homme. Des multiples etudes comportementales indiquent clairement que d’autres mammiferes comme les rats et les souris presentent egalement une preference spontanee pour les boissons et les aliments enrichis en lipides. Jusqu’a une periode recente, on pensait que seules la texture et l’odeur des lipides etaient responsables de leur detection orosensorielle. Cette vision restrictive a ete progressivement remise en question par toute une serie d’etudes recentes suggerant que la gustation contribue egalement a l’attirance pour les lipides. Cette mini-revue se propose de faire le point des connaissances dans ce nouveau domaine d’investigation a la fois chez les rongeurs et chez l’Homme.

Obesity is recognized as a worldwide health problem. Overconsumption of fatty foods contributes significantly to this phenomenon. Rodents, like humans, display preferences for lipid-rich foods. Rodents thus provide useful models to explore the mechanisms responsible for this complex feeding behavior resulting from the integration of multiple oral and postoral signals. Over the last decades, the lipid-mediated regulation of food intake has received considerable attention. By contrast, orosensory lipid perception was long thought to involve only textural and olfactory cues. Recent findings have challenged this limited viewpoint. These recent data strongly suggest that the sense of taste also plays significant roles in the spontaneous preference for fatty foods. This paper provides a brief overview of postoral regulation of food intake by lipids and then highlights recent data suggesting the existence of a "fatty taste" which might contribute to lipid overeating and hence to the risk of obesity.

We define an inference system to capture explanations based on causal statements, using an ontology in the form of an IS-A hierarchy. We first introduce a simple logical language which makes it possible to express that a fact causes another fact and that a fact explains another fact. We present a set of formal inference patterns from causal statements to explanation statements. We introduce an elementary ontology which gives greater expressiveness to the system while staying close to propositional reasoning. We provide an inference system that captures the patterns discussed, firstly in a purely propositional framework, then in a datalog (limited predicate) framework.

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.

Origin of spontaneous fat preference in mammals remains elusive. It is clearly a multimodal system resulting from the integration of orosensory and post-ingestive signals. For a long time, dietary lipids were thought to be only sensed in the oral cavity through their textural and olfactory cues. Recent data strongly suggest that the sense of taste also plays a significant role in the preference for lipid-rich foods and in lipid-mediated induction of cephalic phase of the digestion in rodents and in humans. Molecular and physiological mechanisms of this new paradigm become known. Some of these data were not fully expected and might be considered, as first sight, as paradoxical. The « fatty taste » paradigm and paradoxes are analyzed in this minireview.

VIIe Symposium nutrition – « L'intervention nutritionnelle » : de la prévention à la thérapeutique – Brest, 8 novembre 2006; International audience; Over the two last decades, isolation and characterization of proteins involved in transport and metabolic fate of long-chain fatty acids have provided new insights on the molecular basis of fat absorption. This systematic cloning period has been followed by the functional genomics time which led to surprises. Indeed, disruption of several genes, thought to be crucial for long-chain fatty acid absorption, did not lead to clear phenotypes. This observation raises the question about the real physiological role of several lipid-binding proteins and enzymes found in the enterocyte. This mini-review assesses the present knowledge concerning the main steps of intestinal fat absorption: the cellular uptake and trafficking of long-chain fatty acids and the lipoprotein synthesis.; Les deux dernières décennies ont été marquées par une accumulation de connaissances nouvelles concernant les aspects moléculaires de l'absorption des lipides alimentaires avec l'isolement et la caractérisation de protéines potentiellement impliquées dans le transport et le devenir entérocytaires des acides gras à longue chaîne. À cette période de clonage systématique a succédé celle de la génomique fonctionnelle qui s'avère pleine de surprise puisque l'invalidation de nombreux gènes considérés jusqu'alors comme essentiels pour l'absorption intestinale des lipides ne s'accompagne pas d'un phénotype clair. Ce constat amène à reconsidérer le rôle physiologique exercé, notamment, par les nombreux transporteurs de lipides (lipid-binding proteins) et certaines enzymes exprimés au niveau entérocytaire. Cette mini-revue se propose de faire un état des lieux des faits et incertitudes concernant les principales étapes de l'absorption des acides gras, à savoir leur captage et trafic cellulaire et la synthèse des lipoprotéines intestinales.

An argument is seen as reason in favour of a claim. It is made of three parts: a set of premises representing the reason, a conclusion representing the supported claim, and a connection showing how the premises lead to the conclusion. Arguments are frequently exchanged by human agents in natural language (spoken or written) in discussion, debate, negotiation, persuasion, etc. They may be very different in that their three components may have various forms. In this paper, we propose a language for representing such arguments. We show that it is general enough to capture the various forms of arguments encountered in natural language, and that it is possible to represent attack and support relations between arguments as formulas of the same language.

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.

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 with changes in i) the gross anatomy of CVP, ii) the LCFA-mediated increases in [Ca2+]i, iii) the preference for oily and LCFA solutions and iv) the conditioned avoidance of LCFA solutions. In contrast, the rise in [Ca2+]i triggered by grifolic acid (GA), a specific GPR120 agonist, was dramatically curtailed when GPR120 gene was lacking. Taken together these data demonstrate that activation of lingual GPR120 and preference for fat are disconnected, suggesting that GPR120 expressed in TBC is not absolutely required for the oral fat detection in the mouse.