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International audience; 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.

International audience; Background : Bisphenol S is an endocrine disruptor exhibiting metabolic disturbances, especially following perinatal exposures. To date, no data are available on the obesogen effects of BPS in a mutligenerational issue.Objectives : We investigated obesogen effects of BPS in a multigenerational study by focusing on body weight, adipose tissue and plasma parameters in male and female mice.Methods : Pregnant C57BL6/J mice were exposed to BPS (1.5 μg/kg bw/day ie a human equivalent dose of 0.12 μg/kg bw/day) by drinking water from gestational day 0 to post natal day 21. All offsprings were fed with a high fat diet during 15 weeks. Body weight was monitored weekly and fat mass was measured before euthanasia. At euthanasia, blood glucose, insuline, triglyceride, cholesterol and no esterified fatty acid plasma levels were determined and gene expressions in visceral adipose tissue were assessed. F1 males and females were mated to obtain the F2 generation. Likewise, the F2 mice were cross-bred to obtain F3. The same analyses were performed.Results : In F1 BPS induced an overweight in male mice associated to lipolysis gene expressions upregulation. In F1 females, dyslipidemia was observed. In F2, BPS exposure was associated to an increase in body weight, fat and VAT masses in males and females. Several plasma parameters were increased but with a sex related pattern (blood glucose, triglycerides and cholesterol in males and NEFA in females). We observed a down-regulation in mRNA expression of gene involved in lipogenesis and in lipolysis for females but only in the lipogenesis for males. In F3, a decrease in VAT mass and an upregulation of lipogenesis gene expression occurred only in females.Conclusions : BPS perinatal exposure induced sex-dependent obesogen multigenerational effects, the F2 generation being the most impacted. Transgenerational disturbances persisted only in females.

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 perception in rodents. RESULTS A 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. CONCLUSIONS The 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.

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).

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.

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.