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IntroductionA preferential consumption of low-fat foods is reported by most of the patients after a vertical sleeve gastrectomy (VSG). The fact that a recent study shed light on a relationship between oral microbiota and fat taste sensitivity in obese patients prompted us to explore whether such a connection also exists in the context of a VSG.MethodsThirty-two adult female patients with a severe obesity (BMI = 43.1 ± 0.7 kg/m2) and candidates for a VSG were selected. Oral microbiota composition surrounding the gustatory circumvallate papillae (CVP) and the lipid perception thresholds were explored before and 6 months after surgery.ResultsVSG was found to be associated both with a qualitative (compositional changes) and quantitative (lower gene richness) remodeling of the peri-CVP microbiota. Analysis of the lipid perception allowed us to distinguish two subgroups: patients with a post-operative improvement of the fat taste sensitivity (i.e., with a lower threshold, n = 14) and unimproved patients (n = 18). Specific peri-CVP microbiota signatures also discriminated these two subgroups, unimproved patient being characterized by higher levels of Porphyromonas, Fusobacterium, and Haemophilus genera associated with lower levels of Atopobium and Prevotella genera as compared to the lipid-improved patients.ConclusionCollectively, these data raise the possibility that the microbial environment surrounding gustatory papillae might play a role in the positive changes of fat taste sensitivity observed in some patients after VSG.

This paper explores the computation of explanations in the specific context of abstract argumentation. The explanations that we define are designed to be visual, in the sense that they take the form of subgraphs of the argumentation graph. Moreover, these explanations rely on the modular aspects of abstract argumentation semantics and can consequently be either aggregated or decomposed. We investigate graph properties of these explanations, and their adequacy to desirable explanatory criteria.

In 1995, in his seminal paper introducing the abstract argumentation framework, Dung has also established the first relationship between this framework and a logical framework (in this case: logic programming). Since that time, a lot of work have pursued this path, proposing different definitions, uses and exhibiting distinct relationships between argumentation and logic. In this paper, we present a survey of existing works about this topic and more especially those that address the following question: “How logic has been used for capturing various aspects or parts of Dung’s argumentation”. This survey covers many different approaches but is not intended to be totally exhaustive due to the huge quantity of papers in this scope. Moreover, due to the fact that each approach has its own specificities, sometimes antagonistic with the other approaches, and is also justified by its own context of definition or use, the aim of this survey is not to identify one approach as being better than another.

A preferential consumption of healthier foods, low in fat and sugar, is often reported after bariatric surgery, suggesting a switch of taste-guided food choices. To further explore this hypothesis in well-standardized conditions, analysis of licking behavior in response to oily and sweet solutions has been realized in rats that have undergone a Roux-en-Y bypass (RYGB). Unfortunately, these studies have produced conflicting data mainly due to methodological differences. Paradoxically, whereas the vertical sleeve gastrectomy (VSG) becomes the most commonly performed bariatric surgery worldwide and is easier to perform and standardize in small animals, its putative impacts on the orosensory perception of energy-dense nutrients remains unknown. Using brief-access licking tests in VSG or RYGB mice, we found that (i) VSG induces a significant reduction in the fat mass in diet-induced obese (DIO) mice, (ii) VSG partially corrects the licking responses to lipid and sucrose stimuli which are degraded in sham-operated DIO mice, (iii) VSG improves the willingness to lick oily and sucrose solutions in DIO mice and (iv) RYGB leads to close outcomes. Altogether, these data strongly suggest that VSG, as RYGB, can counteract the deleterious effect of obesity on the orosensory perception of energy-dense nutrients in mice.

Diet-induced obesity (DIO) is associated with a defect of the orosensory detection of dietary lipids in rodents. This dysfunction is not anecdotic since it might worsen the negative effects of obesity by promoting the overconsumption of energy-dense foods. Previous studies have highlighted a progressive devaluation of reward value of lipid stimuli due to a desensitization of dopaminergic brain areas in DIO mice. Paradoxically, the putative deleterious impact of obesity on peripheral fat detection by the gustatory papillae remains poorly documented. Using a whole transcriptomic investigation of the circumvallate papillae (CVP), an analysis of CVP genes involved in fat taste transduction and signaling along the day, and two bottle choice tests, we have found that (i) CVP, known to house the most taste buds in the oral cavity, displays a genic circadian rhythm, (ii) DIO reduces the oscillation of key genes involved both in the circadian clock and lipid detection/signaling, and (iii) the gene invalidation of the clock gene Rev-Erbα does not significantly affect fat preference despite an oily solution intake slightly lower than littermate controls. Taken together these data bring the first demonstration that the gustatory function is under control of a peripheral clock in mammals, as already reported in fly and suggest that a disturbance of this rhythmicity might contribute to the lower fatty taste acuity found in obese mice.

Abstract 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.

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 triglycerides and cholesterol levels were unchanged in mice fed a cholesterol-rich diet that contained 100-fold more cholesterol than the standard diet. In the liver, oxysterol-mediated LXR activation stimulated the synthesis of bile acids and in particular increased the levels of hydrophilic muricholic acids, which in turn reduced FXR signaling, as assessed in vivo with Fxr reporter mice. Consequently, biliary and basolateral excretions of bile acids and cholesterol were increased, whereas portal uptake was reduced. Furthermore, we observed a reduction in intestinal and renal bile acid absorption. Conclusions: These coordinated events are mediated by increased muricholic acid levels which inhibit FXR signaling in favor of LXR and SREBP2 signaling to promote efficient fecal and urinary elimination of cholesterol and neo-synthesized bile acids. Therefore, our data suggest that enhancement of the hydrophilic bile acid pool following a cholesterol overload may contribute to the resistance to hypercholesterolemia in mice. This work paves the way for new therapeutic opportunities using hydrophilic bile acid supplementation to mitigate hypercholesterolemia.

Diet-induced obesity (DIO) reduces the orosensory perception of lipids in rodents and in some humans. Although bariatric surgery partially corrects this alteration, underlying mechanisms remain poorly understood. To explore whether metabolic changes might explain this fat taste disturbance, plasma metabolome analyses, two-bottle choice tests and fungiform papillae (Fun) counting were performed in vertical sleeve gastrectomized (VSG) mice and sham-operated controls. An exploratory clinic study was also carried out in adult patients undergone a VSG. In mice, we found that (i) the VSG reduces both the plasma neurotoxic signature due to the tryptophan/kynurenine (Trp/Kyn) pathway overactivation and the failure of fat preference found in sham-operated DIO mice, (ii) the activity of Trp/Kyn pathway is negatively correlated to the density of Fun, and (iii) the pharmacological inhibition of the Kyn synthesis mimics in non-operated DIO mice the positive effects of VSG (i.e., decrease of Kyn synthesis, increase of Fun number, improvement of the fat taste perception). In humans, a reduction of the plasma Kyn level is only found in patients displaying a post-surgery improvement of their fat taste sensitivity. Altogether these data provide a plausible metabolic explanation to the degradation of the orosensory lipid perception observed in obesity.

The aim of this study was to explore the impact of bariatric surgery on fat and sweet taste perceptions and to determine the possible correlations with gut appetite-regulating peptides and subjective food sensations. Women suffering from severe obesity (BMI > 35 kg/m2) were studied 2 weeks before and 6 months after a vertical sleeve gastrectomy (VSG, n = 32) or a Roux-en-Y gastric bypass (RYGB, n = 12). Linoleic acid (LA) and sucrose perception thresholds were determined using the three-alternative forced-choice procedure, gut hormones were assayed before and after a test meal and subjective changes in oral food sensations were self-reported using a standardized questionnaire. Despite a global positive effect of both surgeries on the reported gustatory sensations, a change in the taste sensitivity was only found after RYGB for LA. However, the fat and sweet taste perceptions were not homogenous between patients who underwent the same surgery procedure, suggesting the existence of two subgroups: patients with and without taste improvement. These gustatory changes were not correlated to the surgery-mediated modifications of the main gut appetite-regulating hormones. Collectively these data highlight the complexity of relationships between bariatric surgery and taste sensitivity and suggest that VSG and RYGB might impact the fatty taste perception differently.

The presence of lipids helps to make food more smooth, creamy and melting, in brief more palatable. This finding is not trivial. It indicates that lipids are easily perceived in a food matrix, which may be complex. During a long time, the oro-sensory detection of dietary lipids was thought to take place only through textural and retronasal olfactory cues. Over the last decade, this restrictive vision has gradually been challenged by a set of animal and human data suggesting that the gustatory pathway may also be involved in this phenomenon. After few reminders about the gustatory pathway, this mini-review will propose a short overview on a controversial question: is there a taste for fat?

Implication of the long-chain fatty acid (LCFA) receptor GPR120, also termed free fatty acid receptor 4, 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 (TBCs)], we show that absence of GPR120 in the oral cavity was not associated with changes in i) gross anatomy of CVP, ii) LCFA-mediated increases in intracellular calcium levels ([Ca2+]i), iii) preference for oily and LCFA solutions and iv) conditioned avoidance of LCFA solutions. In contrast, the rise in [Ca2+]i triggered by grifolic acid, a specific GPR120 agonist, was dramatically curtailed when the GPR120 gene was lacking. Taken together, these data demonstrate that activation of lingual GPR120 and preference for fat are not connected, suggesting that GPR120 expressed in TBCs is not absolutely required for oral fat detection in mice

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).

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 correlation between fat preference and adipose tissue size, iv) obesity suppresses the lipid-mediated downregulation of the lipid-sensor CD36 in circumvallate papillae, usually found during the refeeding of lean mice, and v) the CD36-dependent signaling cascade controlling the intracellular calcium levels ([Ca2+]i) in taste bud cells is decreased in obese mice. Therefore, obesity alters the lipid-sensing system responsible for the oral perception of dietary lipids. This phenomenon seems to take place through a CD36-mediated mechanism, leading to changes in eating behavior.

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 this system, and iv) support the existence of a regulation by GLP-1 of the lipid sensing mediated by lingual CD36. Therefore, oro-sensory detection of LCFAs may affect sweet and fatty taste responsiveness by controlling the secretion of lingual GLP-1. This regulatory loop, probably triggered by the LCFA-GPR120 interaction, might contribute to the high palatability of foods rich both in fat and sugar.

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.

The effects of chronic fat overconsumption on intestinal physiology and lipid metabolism remain elusive. It is unknown whether a fat-mediated adaptation to lipid absorption takes place. To address this issue, mice fed a high-fat diet (40%, w/w) were refed or not a control diet (3%, w/w) for 3 additive weeks. Despite daily lipid intake 7.7-fold higher than in controls, fecal lipid output remained unchanged in mice fed the triglyceride (TG)-rich diet. In situ isolated jejunal loops revealed greater [1-14C]linoleic acid uptake without TG accumulation in mucosa, suggesting an increase in lipid absorption capacity. Induction both in intestinal mitotic index and in the expression of genes involved in fatty acid uptake, trafficking, and lipoprotein synthesis was found in high-fat diet mice. These changes were lipid-mediated, in that they were fully abolished in mice refed the control diet. A lipid load test performed in the presence or absence of the LPL inhibitor tyloxapol showed a sustained blood TG clearance in fat-fed mice likely attributable to intestinal modulation of LPL regulators (apolipoproteins C-II and C-III). These data demonstrate that a chronic high-fat diet greatly affects intestinal physiology and body lipid use in the mouse.

Conjugated linoleic acids (CLA) are a class of positional, geometric, conjugated dienoic isomers of linoleic acid (LA). Dietary CLA supplementation results in a dramatic decrease in body fat mass in mice, but also causes considerable liver steatosis. However, little is known of the molecular mechanisms leading to hepatomegaly. Although c9,t11- and t10,c12-CLA isomers are found in similar proportions in commercial preparations, the respective roles of these two molecules in liver enlargement has not been studied. We show here that mice fed a diet enriched in t10,c12-CLA (0.4% w/w) for 4 weeks developed lipoatrophy, hyperinsulinemia, and fatty liver, whereas diets enriched in c9,t11-CLA and LA had no significant effect. In the liver, dietary t10,c12-CLA triggered the ectopic production of peroxisome proliferator-activated receptor γ (PPARγ), adipocyte lipid-binding protein and fatty acid transporter mRNAs and induced expression of the sterol responsive element-binding protein-1a and fatty acid synthase genes. In vitro transactivation assays demonstrated that t10,c12- and c9,t11-CLA were equally efficient at activating PPARα, β/δ, and γ and inhibiting liver-X-receptor.Thus, the specific effect of t10,c12-CLA is unlikely to result from direct interaction with these nuclear receptors. Instead, t10,c12-CLA-induced hyperinsulinemia may trigger liver steatosis, by inducing both fatty acid uptake and lipogenesis.

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 observed in presence of IL. No IL- or SSO-mediated satiety occurred in CD36-null mice. To determine whether the CD36-mediated hypophagic effect of lipids was maintained in animals fed a satietogen diet, mice were subjected to a High-Protein diet (HPD). Concomitantly with the satiety effect, a rise in intestinal CD36 gene expression was observed. No satiety effect occurred in CD36-null mice. HPD-fed WT mice showed a diminished FI compared to control mice, after saline duodenal infusion. But there was no further decrease after lipid infusion. The lipid-induced decrease in FI observed on control mice was accompanied by a rise in jejunal oleylethanolamide (OEA). Its level was higher in HPD-fed mice than in controls after saline infusion and was not changed by lipids. Overall, we demonstrate that lipid binding to intestinal CD36 is sufficient to produce a satiety effect. Moreover, it could participate in the satiety effect induced by HPD. Intestine can modulate FI by several mechanisms including an increase in OEA production and CD36 gene expression. Furthermore, intestine of mice adapted to HPD have a diminished capacity to modulate their food intake in response to dietary lipids.

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 diurnal rhythms in the gustatory circumvallate papillae, CD36 mRNA levels being down-regulated during the dark period in contrast to GPR120, 2°) this change is due to food intake and strictly dependent of the presence of lipids in the diet, 3°) CD36 protein levels are also rapidly but transiently decreased by the food intake, a two-fold drop in CD36 protein levels being found 1 h after refeeding, followed by a progressive return to the pre-prandial values, 4°) this down-regulation, which has a post-transcriptional origin, seems sufficient to alter the spontaneous fat preference, independently to change in the GPR120 gene expression. CONCLUSIONS/SIGNIFICANCE: In contrast to GPR120, CD36 appears to be a food-sensitive lipid sensor in the gustatory circumvallate papillae. Lipid-mediated change in lingual CD36 expression might modulate the motivation for fat during a meal, initially high and then gradually decreasing secondary to the food intake. This short-term lipid-mediated effect is reminiscent of sensory-specific satiety. These findings, which highlight the role played by CD36 in the oro-sensory perception of dietary lipids, raise the possibility of novel pharmacological strategies to modify attraction for fatty foods and decrease obesity risks.