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International audience; Background & aimsIn most cases, Roux-en-Y gastric bypass (RYGBP) is an efficient intervention to lose weight, change eating behavior and improve metabolic outcomes in obese patients. We hypothesized that weight loss induced by RYGBP in obese Yucatan minipigs would induce specific modifications of the gut–brain axis and neurocognitive responses to oral sucrose stimulation in relationship with food intake control.MethodsAn integrative study was performed after SHAM (n = 8) or RYGBP (n = 8) surgery to disentangle the physiological, metabolic and neurocognitive mechanisms of RYGBP. BOLD fMRI responses to sucrose stimulations at different concentrations, brain mRNA expression, cecal microbiota, and plasma metabolomics were explored 4 months after surgery and integrated with WGCNA analysis.ResultsWe showed that weight loss induced by RYGBP or SHAM modulated differently the frontostriatal responses to oral sucrose stimulation, suggesting a different hedonic treatment and inhibitory control related to palatable food after RYGBP. The expression of brain genes involved in the serotoninergic and cannabinoid systems were impacted by RYGBP. Cecal microbiota was deeply modified and many metabolite features were differentially increased in RYGBP. Data integration with WGCNA identified interactions between key drivers of OTUs and metabolites features linked to RYGBP.ConclusionThis longitudinal study in the obese minipig model illustrates with a systemic and integrative analysis the mid-term consequences of RYGBP on brain mRNA expression, cecal microbiota and plasma metabolites. We confirmed the impact of RYGBP on functional brain responses related to food reward, hedonic evaluation and inhibitory control, which are key factors for the success of anti-obesity therapy and weight loss maintenance.

This study aimed to compare the gut-brain axis responses to acute electroacupuncture (EA) at different acupoint combinations in the minipig model. Four adult Yucatan minipigs were subjected twice to four acute EA treatments (25-minute acute sessions) including sham (false acupoints) and control (no EA), during anesthesia and according to a Latin-square design paradigm. Acupoint combinations (4 loci each) are head-abdomen (#70 Dafengmen, #35 Sanwan), back (bilateral #27 Pishu, #28 Weishu), leg (bilateral #79 Hangou, #63 Housanli), and sham (2 bilateral points that are not acupoints). Electrocardiograms were performed to explore heart rate variability (HRV). Infrared thermography was used to measure skin temperature at the stimulation points. Saliva (cortisol) and blood samples (leptin, total/active ghrelin, insulin, and glucose) were collected for further analyses before and after acute EA. All animals were also subjected to BOLD fMRI to investigate the brain responses to EA. Acute EA significantly modulated several physiological and metabolic parameters compared to basal, sham, and/or control conditions, with contrasting effects in terms of BOLD responses in brain regions involved in the hedonic and cognitive control of food intake. The head-abdomen combination appeared to be the most promising combination in terms of brain modulation of the corticostriatal circuit, with upregulation of the dorsolateral prefrontal cortex, dorsal striatum, and anterior cingulate cortex. It also induced significantly lower plasma ghrelin levels compared to sham, suggesting anorectic effects, as well as no temperature drop at the stimulation site. This study opens the way to a further preclinical trial aimed at investigating chronic EA in obese minipigs.

International audience; The impact of body composition (BC) on the prognosis of resected intrahepatic cholangiocarcinoma (ICC) has been poorly studied. Aims: i) to evaluate the prevalence of low muscle mass (MM) in patients; ii) to assess the impact of BC on patient overall survival (OS) and disease-free survival (DFS), and iii) on the incidence of postoperative complications. All consecutive patients who underwent liver resection for ICC between 2004 and 2016 and who had preoperative CT scans were included. Ninety-three patients were included. Sixty percent (55/91) had low total MM. On multivariable analysis, high visceral fat (HR 2.48, CI95% [1.63; 3.77], p 1 (HR 3.15 [1.67; 5.93], p = 0.0004), involvement adjacent organ (HR 6.67 [1.88; 23.69], p = 0.003), and postoperative sepsis (HR 3.04 [1.54; 5.99], p = 0.0013) were independently associated with OS. High visceral fat (HR 2.10 [1.31; 3.38], p = 0.002], nodules >1 (HR 3.01, [1.49; 6.10], p = 0.002), postoperative sepsis (HR 5.16 [2.24; 11.89], p = 0.0001), ASA score (p = 0.02) and perineural invasion (HR 3.30 [1.62; 6.76], p = 0.001) were independently associated with lower DFS. Conclusion: 60% of ICC patients had low MM before surgery. High visceral fat, but not muscle mass, was an independent prognostic factor for poor OS and DFS in European patients with resected ICC.

International audience; Emotional eating is commonly defined as the tendency to (over)eat in response to emotion. Insofar as it involves the (over) consumption of high-calorie palatable foods, emotional eating is a maladaptive behavior that can lead to eating disorders, and ultimately to metabolic disorders and obesity. Emotional eating is associated with eating disorder subtypes and with abnormalities in emotion processing at a behavioral level. However, not enough is known about the neural pathways involved in both emotion processing and food intake. In this review, we provide an overview of recent neuroimaging studies, highlighting the brain correlates between emotions and eating behavior that may be involved in emotional eating. Interaction between neural and neuro-endocrine pathways (HPA axis) may be involved. In addition to behavioral interventions, there is a need for a holistic approach encompassing both neural and physiological levels to prevent emotional eating. Based on recent imaging, this review indicates that more attention should be paid to prefrontal areas, the insular and orbitofrontal cortices, and reward pathways, in addition to regions that play a major role in both the cognitive control of emotions and eating behavior. Identifying these brain regions could allow for neuromodulation interventions, including neurofeedback training, which deserves further investigation.

Performing the Roux-en-Y gastric bypass (RYGBP) in obese Yucatan minipigs provides an opportunity to explore the mechanisms behind the effects of this surgery in controlled environmental and nutritional conditions. We hypothesized that RYGBP in these minipigs would induce changes at multiple levels, as in obese humans. We sought to characterize RYGBP in a diet-induced obese minipig model, compared with a pair-fed sham group. After inducing obesity with an ad libitum high-fat/high-sugar diet, we performed RYGBP (n = 7) or sham surgery (n = 6). Oral glucose tolerance tests (OGTT) were performed before and after surgery. Histological analyses were conducted to compare the alimentary limb at sacrifice with tissue sampled during RYGBP surgery. One death occurred in the RYGBP group at postoperative day (POD) 3. Before sacrifice, weight loss was the same across groups. GLP-1 secretion (OGTT) was significantly higher at 15, 30 and 60 min at POD 7, and at 30 and 60 min at POD 30 in the RYGBP group. Incremental insulin area under the curve increased significantly after RYGBP (p = 0.02). RYGBP induced extensive remodeling of the alimentary limb. Results show that RYGBP can be safely performed in obese minipigs, and changes mimic those observed in humans.

International audience; Background & aimsSevere malnutrition exposes patients to adverse outcomes and a higher mortality risk. The Yucatan minipig, closer to human physiology than murine models could be a pertinent and innovative experimental model for studying the physiopathology and consequences of severe malnutrition. The present study aimed to determine whether a low calorie/low protein diet (LC/LP) can reproduce marasmus malnutrition in minipigs, and to characterize body composition, gut microbiota, malnutrition-related blood parameters, and histological and molecular skeletal muscle patterns.MethodsEleven Yucatan minipigs were subjected to two different diets: a standard control diet (ST) (n = 5) and a LC/LP diet (n = 6). LC/LP animals daily received 50% of an isocaloric low-protein diet (10.37 MJ/kg, 8.6% protein). Body composition was measured by computed tomography (CT-scan) before (T0) and after 8 weeks of diet (T8). Trapezius and biceps femoris muscles were sampled at the end of protocol to perform histological and molecular analyses. Gut microbiota composition were was also analyzed at T0 and T8 in fecal samples.ResultsEight weeks of LC/LP diet significantly reduced body weight (−12.3 ± 9.5%, P = 0.03) and gut microbiota richness (i.e. number of observed species) (−10.4 ± 8.3%, P = 0.014) compared to baseline. After 8 weeks, LC/LP animals exhibited a significant reduction of retroperitoneal fat and skeletal muscle surface areas (P = 0.03 and P = 0.047, respectively), whereas these parameters remained unchanged in ST animals. These reductions were associated with lower muscle fiber cross-sectional area (CSA) in trapezius (P < 0.001) and biceps femoris (P = 0.003) in LC/LP animals compared to ST. LC/LP diet promoted an increase of AMP kinase phosphorylation in trapezius and biceps femoris (P = 0.05), but did not affect cytochrome c and COX IV protein content, markers of mitochondrial content. Gene and proteins involved in ubiquitin-proteasome system and apoptosis remained unchanged after 8 weeks of LC/LP diet both in trapezius and biceps femoris.ConclusionAll these findings support that this experimental minipig model of severe malnutrition is valid to mimic pathophysiological changes occurring in human protein-energy marasmus malnutrition and muscle atrophy associated with malnutrition, as observed in patients with secondary sarcopenia.

International audience; In the context of obesity, little is known about the prevalence of food addiction nor about the phenotype of obese patients with food addiction. : To assess: (i) the prevalence of food addiction among obese patients eligible for obesity surgery; (ii) the relationship between clinical features and the complications of obesity. : Consecutive patients consulting for the first time were included. The Yale Food Addiction Scale (YFAS) 2.0 questionnaire was used to diagnose food addiction and its severity. Demographics, clinical features, and obesity complications were systematically collected. Statistics: Student's test was used for numerical variables and Chi-square test or Fisher's exact test for categorical variables. : A total of 292 patients were included: 79% female, age (mean ± SD) 42.6 ± 13.0 yrs., body mass index (BMI) 43.2 ± 6.8 kg/m. One hundred and eight patients (37%) had food addiction: 58% severe, 33% moderate, 9% mild. Food addiction prevalence was 39% (n = 61/156) among patients eligible for obesity surgery. Food addiction was more frequent among the unemployed, compared to professionally active patients (41.0% . 33.5%, p = 0.046). Clinical and metabolic phenotypes and obesity complications were similar between patients with and without food addiction. : Food addiction was present in 37% of obese patients, but was not associated with clinical features or obesity complications. Therefore, it should be systemically assessed for appropriate management.

International audience; We examined the relationship between boredom proneness and psychological distress in patients receiving hospital care due either to excessive alcohol consumption or to gastrointestinal diseases. Sociodemographic data were collected together with boredom proneness subscales (internal/external lack of stimulation), psychological distress, physical activity, and social support. Boredom proneness due to a lack of external stimulation seemed to constitute a prominent personality trait in patients with alcohol consumption. But depressive symptoms were related only to boredom proneness due to a lack of internal stimulation in all patients, regardless of alcohol status, lifestyle, or social support. Potential implications for practice and future research are discussed.

Acupuncture has thousands of years of history and perspective for the treatment of many health problems and disorders. Beneficial effects of acupuncture on obesity have been demonstrated at various levels in animals and clinical trials, with almost no adverse effect, even when combined with local electrical stimulation, i.e., electroacupuncture (EA), a way to potentiate the effects of acupuncture. However, there is still scattered evidence about the impact of EA on brain functions related to the control of eating behavior, and notably on the gut–brain axis mechanisms involved in these putative central modulations. During the past 10 years, we have described a convincing diet-induced obese minipig model, and successfully implemented brain imaging and neurocognitive approaches to challenge mechanistic hypotheses and innovative therapeutic strategies. In the present article, we propose to confront the current literature on the acupuncture and EA effects on the gut–brain axis and obesity with the latest developments in nutrition and neuroscience research using the minipig model. Our aims are to (a) elaborate functional hypotheses on the gut–brain mechanisms underlying EA effects on obesity, and especially on the role of the vagus nerve, and (b) present the rational for testing these hypotheses in the minipig model.

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International audience; Introduction: N3 polyunsaturated fatty acids (n-3 PUFAs) exert anti-inflammatory effects for the hypothalamus, but their extra-hypothalamic outcome lack documentation. We evaluated the central consequences of the substitution of saturated fatty acids with n-3 or n-6 PUFA in obesogenic diets.Methods: Twenty-one miniature pigs were fed ad libitum obesogenic diets enriched in fat provided either as lard, fish oil (source for n-3 PUFAs), or sunflower oil (source for n-6 PUFAs) for ten weeks. The blood-brain barrier (BBB) permeability was quantified by CT perfusion. Central autonomic network was evaluated using heart rate variability, and PET 18FDG was performed to assess brain metabolism.Results: BBB permeability was higher in lard group, but heart rate variability changed only in fish oil group. Brain connectivity analysis and voxel-based comparisons show regional differences between groups except for the cingulate cortex in fish oil vs. sunflower oil groups.Discussion: : The minute changes in brain metabolism in obese pigs feed with fish oil compared with saturated fatty acids were sufficient to induce detrimental changes in heart rate variability. On the contrary, the BBB's decreased permeability in n-3 and n-6 PUFAs groups was protective against an obesity-driven damaged BBB.

International audience; BACKGROUND: Uterine transplant (UT) represents an opportunity to treat absolute uterine infertility. However, the use of uterine veins for venous return, in addition to ovarian veins, significantly increases the risk of ureteral wounds in the living donor and UT time for the recipient. Our aim was to demonstrate that dual ovarian venous return is sufficient for graft viability and survival. METHODS: Uterine orthotopic auto-transplant was performed under general anaesthesia in six Yucatan minipig sows. The uterus graft was implanted with termino-lateral anastomoses between the ovarian and external iliac veins, and between the uterine and external iliac arteries, respectively. RESULTS: The macroscopic physical aspect of the graft was adequate in 83 % of the sows (5/6) 30 min after reperfusion with a surgical time of 439±54 min (mean anastomosis time: 153±49 min). Two sows died the day after surgery. In the four remaining sows, two uteri were necrotic and two were adequately vascularized on Day 7. CONCLUSIONS: the learning curve was relatively fast, the sole use of bilateral ovarian venous return is possible and might reduce post-surgery morbidity in human living donors as well as UT time for the recipient.

International audience; Obesity and related diseases are considered as pandemic representing a worldwide threat for health. Animal models are critical to validate the effects and understand the mechanisms related to classical or innovative preventive and therapeutic strategies. It is, therefore, important to identify the best animal models for translational research, using different evaluation criteria such as the face, construct, and predictive validity. Because the pharmacological treatments and surgical interventions currently used for treating obesity often present many undesirable side effects, relatively high relapse probabilities, acupuncture, electroacupuncture (EA), and related therapies have gained more popularity and attention. Many kinds of experimental animal models have been used for obesity research studies, but in the context of acupuncture, most of the studies were performed in rodent obesity models. Though, are these obesity rodent models really the best for acupuncture or related therapies research studies? In this study, we review different obesity animal models that have been used over the past 10 years for acupuncture and EA research studies. We present their respective advantages, disadvantages, and specific constraints. With the development of research on acupuncture and EA and the increasing interest regarding these approaches, proper animal models are critical for preclinical studies aiming at developing future clinical trials in the human. The aim of the present study is to provide researchers with information and guidance related to the preclinical models that are currently available to investigate the outcomes of acupuncture and related therapies.

Palatable sweet/fatty foods overconsumption is a major risk factor for obesity and eating disorders, also having an impact on neuro-behavioural hedonic and cognitive components comparable to what is described for substance abuse. We hypothesized that Yucatan minipigs would show hedonic, cognitive, and affective neuro-behavioral shifts when subjected to western diet (WD) exposure without weight gain, after the onset of obesity, and finally after weight loss induced by caloric restriction with (RYGB) or without (Sham) gastric bypass. Eating behavior, cognitive and affective abilities were assessed with a spatial discrimination task (holeboard test) and two-choice feed tests. Brain responses to oral sucrose were mapped using 18F-FDG positron emission tomography. WD exposure impaired working memory and led to an “addiction-type” neuronal pattern involving hippocampal and cortical brain areas. Obesity induced anxiety-like behavior, loss of motivation, and snacking-type eating behavior. Weight loss interventions normalized the motivational and affective states but not eating behavior patterns. Brain glucose metabolism increased in gustatory (insula) and executive control (aPFC) areas after weight loss, but RYGB showed higher responses in inhibition-related areas (dorsal striatum). These results showed that diet quality, weight loss, and the type of weight loss intervention differently impacted brain responses to sucrose in the Yucatan minipig model.

Introduction et but de l’etude Chez le patient obese, les troubles du comportement alimentaire sont frequents, et parfois associes au diagnostic d’addiction alimentaire (AA). Leur meconnaissance pourrait expliquer l’echec de la prise en charge. Peu de donnees existent sur la prevalence et le phenotype metabolique des patients obeses ayant une AA. Son diagnostic repose sur le questionnaire Yale Food Addiction Scale (YFAS) 2.0. Objectifs dans une population de patients obeses presentant les criteres d’eligibilite a la chirurgie de l’obesite, determiner la prevalence de l’AA, le phenotype clinique et metabolique des patients AA, determiner les facteurs impliques dans la reponse au traitement de l’obesite dont l’AA. Materiel et methodes Tous les patients obeses consultant pour la 1re fois dans notre unite de nutrition de decembre 2016 a mars 2019 ont ete inclus. Le questionnaire YFAS 2.0 a ete rempli par chaque patient, et leurs donnees sociodemographiques, cliniques et metaboliques ont ete collectees. Le succes du traitement nutritionnel pre-operatoire a ete evalue a 6 mois et/ou 1 an par la perte de poids (a 6 mois : > 5 % du poids initial ou > 25 % de l’exces de poids, a 1 an : > 10 % du poids initial ou > 50 % de l’exces de poids). Statistique : t Student, Mann–Whitney, Wilcoxon, Chi2, Fisher exact. Analyses univariee et multivariee pour determiner les variables impliquees dans la reponse au traitement. Resultats et analyse statistique Parmi les 384 questionnaires distribues, 292 ont ete analyses (taux de non remplissage : 24 %) : 80 % de femmes, âge moyen 42,6 ± 13,0, ans, indice de masse corporelle (IMC) moyen, 43,2 ± 6,8. La prevalence de l’AA etait de 37 % (n = 108) dans l’ensemble de notre population. Parmi ceux-ci, 58 % avait une AA severe, 33 %, moderee et 9 %, legere. L’AA touchait davantage les patientes sans emploi que celles actives (41 % versus 33,5 % p = 0,046). Le profil clinique et metabolique ainsi que la prevalence des complications medicales de l’obesite, ne differaient pas entre AA et non AA. En analyse multivariee, l’âge (OR = 1,56 [1,14 ; 2,14], p = 0,0058), l’IMC (OR = 1,29 [1,01 ; 1,65], p = 0,0378) ainsi que les douleurs articulaires (OR = 3,10 [1,15 ; 8,35, p = 0,0248]), mais pas l’AA, etaient significativement associes a un moindre succes de la perte de poids a 6 mois et/ou 1 an. Conclusion Trente-sept pour cent des patients obeses consultant pour la 1re fois dans notre centre rapportaient une AA. Nous n’avons pas identifie de phenotype sociodemographique, clinique ou metabolique du patient obese avec AA. L’AA n’etait pas associee a la severite de l’obesite ou a ses comorbidites et n’etait pas predictive du succes du traitement.

International audience; Psychological chronic stress is associated with the development of mood disorders, and spices have shown protective properties in this context. This research investigated the effects of a supplementation with a functional food ingredient containing spice extracts in a pig model of psychosocial chronic stress. Its impact on behavior, neurophysiology, immune system and gastrointestinal tract were evaluated. Almost no significant results were found at the gut and immune levels. An increased expression of 5-HT1AR and BDNF in the hippocampus and prefrontal cortex, respectively, and blood perfusion changes in several brain regions including the olfactory bulb, hippocampus, dorsolateral prefrontal cortex and dorsal anterior cingulate cortex were observed. Also, slight anxiolytic-like effects were observed in the Open-field and Novelty-Suppressed Feeding tests. These modulations of brain regions associated with the regulation of emotions and cognition as well as the potential effects on anxiety might come from the repeated stimulation of the olfactory system.

Introduction The pig is a good model for human nutrition research, especially in the neonatal period. Our objective was to validate behavioral tests and get reference values on various components of eating behavior in young minipigs. Methods After 1 week of habituation to 2% sucrose standard (STD) or 20% sucrose (HS) isocaloric pig diets, feed preference for STD or HS were tested 5 times in 5-week-old Yucatan minipigs (n = 15) by offering ad libitum access to the two feeds during 30 min, either in a fasted (overnight) or a fed (30 min after a meal) state. The time spent eating, sniffing or foraging the two diets, as well as non-nutritive behaviors were recorded. In a second test (repeated 20 times), piglets’ strategy when confronted with a choice between a small amount of HS (13 kcal) vs. a large amount of STD (93 kcal) was assessed in a T-maze. A preference for one of the two nutritional rewards was defined when the same reward was chosen more than 14 times out of the 20. Results Piglets displayed a clear preference towards HS as shown by the first feed chosen (HS chosen first out of 5 trials: fasted 4.1 ± 1.1, fed 4.4 ± 0.5) and the amount of feed eaten (fasted: HS 67 ± 6 vs STD 10 ± 2 g, P Conclusion Young Yucatan minipigs have a clear preference for a sweet compared to a standard feed when given access to both feeds. However, when confronted with a dietary choice, unlateralized piglets chose preferentially a large amount of STD over a small amount of HS. These new behavioral tests will be valuable to assess the impact of early nutrition on the development of eating behavior.

Natural plant extracts are increasingly used as functional feed ingredients in animal husbandry and food ingredients in human alternative medicine to improve welfare and health. We investigated in 20 growing pigs via functional magnetic resonance imaging (fMRI) the brain blood oxygen level-dependent (BOLD) responses to olfactory stimulation with two sensory functional feed ingredients, A and B, at two different concentrations. Functional ingredient A contained extracts from Citrus sinensis (60% to 80%), and ingredient B contained a mixture of extracts Oreganum vulgarae (40% to 55%) and Cymbopogon flexuosus (20% to 25%). Increased concentration of ingredients induced a higher activation in reward and cognitive areas compared to lower concentrations. Moreover, considering both ingredients at the highest concentration, the ingredient A elicited higher brain responses in brain areas involved in hedonism/pleasantness compared to ingredient B, and more specifically in the caudate nucleus and orbitofrontal cortex. Our findings shed new light in the scope of emotion regulation through olfactory modulation via sensory functional ingredients, which opens the way to further preclinical studies in animal models and translational research in the context of nutrition, welfare, and health. PRACTICAL APPLICATION: Functional food/feed ingredients are gaining interest for improving health and welfare in humans and animals. Besides representing an alternative to antibiotics for example, food ingredients and their sensory characteristics might have a positive impact on emotions and consequently on well-being. Functional brain imaging in large animals such as in the pig model is a promising approach to investigate the central and behavioural effects of food ingredients, and determine the most effective blends and concentrations to modulate internal and emotional states.

International audience; Oleoylethanolamide is a well-recognized anorectic compound which also has noteworthy effects on food-reward, influencing the acetylcholine (ACh)/dopamine (DA) balance in the cholinergic system. After its administration, oleoylethanolamide is quickly degraded into oleic acid and ethanolamine. The effect of oleic acid on the gut-brain axis has been extensively investigated, whereas ethanolamine has received scarce attention. However, there is scattered evidence from old and recent research that has underlined the influence of ethanolamine on the cholinergic system. In the present article, we propose a model by which the released ethanolamine contributes to the overall balance between DA and ACh after oleoylethanolamide administration.

Discipline Clinique. Introduction et but de l’etude L’obesite est une pandemie responsable de nombreuses complications. L’addiction alimentaire (AA) est un concept recent pouvant expliquer en partie l’echec de la prise en charge de l’obesite. L’objectif de notre etude etait donc de determiner la prevalence de l’AA dans une population de patients obeses eligibles a la chirurgie de l’obesite, et le phenotype clinique du patient obese ayant une AA. Materiel et methodes Le Yale Food Addiction Scale (YFAS) 2,0 est le questionnaire valide qui a ete utilise pour le diagnostic d’AA. Il etait rempli par chaque nouveau patient consultant dans l’unite de nutrition pour la prise en charge d’une obesite. Les donnees sociodemographiques et cliniques etaient collectees retrospectivement a partir de patients obeses vus en consultation de nutrition de decembre 2016 a mars 2018. Tous les patients ayant rempli le questionnaire YFAS ont ete inclus dans l’analyse. Les donnees qualitatives etaient analysees a l’aide du test du Chi2 ou Fisher exact et les donnees quantitatives par l’analyse de variance a un facteur (ANOVA). Resultats et analyse statistique Deux cent vingt-six patients obeses ont rempli le questionnaire YFAS 2,0. Parmi ces patients, 44 (19 %) ont ete exclus de l’analyse car les questionnaires etaient mal remplis. Quatre-vingt pour cent etaient des femmes. L’âge moyen etait de 43,3 ans (± 13,7). L’indice de masse corporelle (IMC) moyen etait de 42,9 kg/m2 (± 6,6). La prevalence d’AA etait de 33 % (n = 60/182). Parmi ceux-ci, 57 % avait une AA severe, 35 % une moderee et 8 % une legere. Parmi les patients eligibles a une chirurgie de l’obesite 39 % (n = 34/88) avaient une AA. L’AA touchait davantage les femmes et cela de maniere significative : 37 % des femmes et 17 % des hommes (p = 0,02). Les donnees sociodemographiques telles que l’âge, la profession, le statut marital, la parentalite, le lieu de residence et l’IMC ne differaient significativement pas entre AA et non AA. Il en etait de meme pour la prevalence des complications medicales (diabete, hypertension arterielle, infarctus du myocarde, syndrome metabolique, dyslipidemie, steatose hepatique, syndrome d’apnees obstructives du sommeil, dyspnee). Conclusion Pres de 40 % des patients obeses eligibles a la chirurgie de l’obesite et adresses dans notre centre de reference rapportaient une AA. Cependant, l’AA n’etait pas associee aux complications de l’obesite. Il reste maintenant a determiner si la presence d’une AA est ou non predictive du succes de la prise en charge medico-chirurgicale de l’obesite, et si une prise en charge addictologique personnalisee dediee permettrait le maintien de la perte de poids a long terme.

The functional roles of the Caudate nucleus (Cd) are well known. Selective Cd lesions can be found in neurological disorders. However, little is known about the dynamics of the behavioral changes during progressive Cd ablation. Current stereotactic radiosurgery technologies allow the progressive ablation of a brain region with limited adverse effects in surrounding normal tissues. This could be of high interest for the study of the modified behavioral functions in relation with the degree of impairment of the brain structures. Using hypofractionated stereotactic radiotherapy combined with synchrotron microbeam radiation, we investigated, during one year after irradiation, the effects of unilateral radio-ablation of the right Cd on the behavior of Yucatan minipigs. The right Cd was irradiated to a minimal dose of 35.5 Gy delivered in three fractions. MRI-based morphological brain integrity and behavioral functions, i.e. locomotion, motivation/hedonism were assessed. We detected a progressive radio-necrosis leading to a quasi-total ablation one year after irradiation, with an additional alteration of surrounding areas. Transitory changes in the motivation/hedonism were firstly detected, then on locomotion, suggesting the influence of different compensatory mechanisms depending on the functions related to Cd and possibly some surrounding areas. We concluded that early behavioral changes related to eating functions are relevant markers for the early detection of ongoing lesions occurring in Cd-related neurological disorders.

Psychosocial chronic stress is a critical risk factor for the development of mood disorders. However, little is known about the consequences of acute stress in the context of chronic stress, and about the related brain responses. In the present study we examined the physio-behavioural effects of a supplementation with a sensory functional food ingredient (FI) containing Citrus sinensis extract (D11399, Phodé, France) in a pig psychosocial chronic stress model. Female pigs underwent a 5- to 6-week stress protocol while receiving daily the FI (FI, n = 10) or a placebo (Sham, n = 10). We performed pharmacological magnetic resonance imaging (phMRI) to study the brain responses to an acute stress (injection of Synacthen®, a synthetic ACTH-related agonist) and to the FI odour with or without previous chronic supplementation. The olfactory stimulation with the ingredient elicited higher brain responses in FI animals, demonstrating memory retrieval and habituation to the odour. Pharmacological stress with Synacthen injection resulted in an increased activity in several brain regions associated with arousal, associative learning (hippocampus) and cognition (cingulate cortex) in chronically stressed animals. This highlighted the specific impact of acute stress on the brain. These responses were alleviated in animals previously supplemented by the FI during the entire chronic stress exposure. As chronic stress establishes upon the accumulation of acute stress events, any attenuation of the brain responses to acute stress can be interpreted as a beneficial effect, suggesting that FI could be a viable treatment to help individuals coping with repeated stressful events and eventually to reduce chronic stress. This study provides additional evidence on the potential benefits of this FI, of which the long-term consequences in terms of behaviour and physiology need to be further investigated.

International audience; Changes in microglial development and morphology can be induced by inflammatory conditions and associated with eating or mood disorders, such as hyperphagia or depression. In a previous paper in the minipig model, we showed that maternal Western diet during gestation and lactation decreased hippocampus neurogenesis and food-rewarded cognitive abilities in the progeny. Whether these alterations are concomitant with a central inflammatory process in brain structures involved in learning and memory (hippocampus, HPC), cognitive (prefrontal cortex, PFC), or hedonic (orbitofrontal cortex, OFC) control of food intake is still unknown. In the present study, Yucatan minipigs (Sus scrofa) sows were exposed to two different diets during gestation and lactation (standard, SD N = 7 vs. Western diet, WD N = 9). Iba1 is a calcium-binding protein specifically expressed in microglia in the brain, which plays an important role in the regulation of the microglia function. Iba1 expression was examined by immunohistochemical analyses in the PFC, OFC and HPC of piglets. The density of microglial cells, as well as their morphology, were assessed in order to have an indirect insight of microglial cell activation state possibly in relationship with neuroinflammation. The density of Iba1-positive cells was higher in the PFC but not in the HPC of WD compared to SD piglets (p

Introduction et but de l’etude Une meilleure comprehension de la physiopathologie de la denutrition justifie le developpement de modeles precliniques. Objectif principal : caracteriser les changements de composition corporelle (CC) lors de la denutrition chronique chez un modele miniporc denutri. Objectifs secondaires : comparer les phenotypes de CC, identifier les changements moleculaires et de microbiote intestinal entre des animaux denutris et non denutris, en reponse aux differents regimes. Materiel et methodes Seize miniporcs Yucatan (mâles = 3) ont ete inclus et soumis a 3 types de regimes : groupe ST (n = 5) :regime standard (10.33 MJ/kg, 15 % proteines), groupe HN (n = 5) : regime hypocalorique normoproteique (5,16 MJ/kg, 15 %), groupe HH un regime hypocalorique hypoproteique (5,18 MJ/kg, 8,6 % proteines) pendant 2 mois. La CC a ete mesuree sur une coupe scannographique centree sur la 13e vertebre thoracique a T0, 4 et 8 semaines. Ont ete effectues a T8 : analyse par PCR en temps reel des genes Akt,mTOR, JAK1, murf1 et les types de myosine sur les muscles Biceps Femoris (BF), Longissimus Dorsi (LD) et trapeze (T), concentration des selles en acides gras a chaines courtes (AGCC) et une comparaison du microbiote intestinal (ARN 16S) a T0, T4 et T8. Accord du comite d’ethique pour ce travail. Resultats et analyse statistique Il n’existait pas de difference significative entre les 3 groupes a T0 concernant la surface musculaire (SM), la surface de graisse viscerale (SGV) et la surface de graisse sous-cutanee (SGSC). A T4 : baisse de la SM entre HH (p = 0,006) et HN versus ST (p = 0,03) sans modification de la SGV et de la SGSC. A T8, il n’y avait plus de difference entre les groupes. 1animal du groupe HN a du etre euthanasie en raison d’une denutrition severe et chez 2 animaux du groupe HH et 1 animal du groupe ST, la graisse SC etait non quantifiable (trop faible) a T8.Il existait des differences d’expression genique : diminution Akt dans le T groupe ST vs HH (p = 0,04), augmentation mTOR et Murf1 dans le LD groupe HN vs ST (p = 0,009), augmentation JAK1 dans le T groupe HN vs ST (p = 0,0174), diminution myosine 2b dans le LD groupe HN vs ST (p = 0,26). Il n’existait pas de difference significative d’AGCC a T0, mais a T8, les AGCC etaient significativement plus eleves dans le groupe HH par rapport au groupe HN (p = 0,03). Il existait une diminution significative de la richesse du microbiote a T8 regime HH (p = 0,36) alors qu’il n’existait pas de difference a T0 entre les 3 groupes. Conclusion Nos regimes s’accompagnent d’une diminution de masse musculaire a T4 non retrouvee a T8. Un animal du groupe HN a du etre euthanasie en raison d’une mauvaise tolerance avec denutrition clinique severe. L’augmentation de l’expression de Murf1, proteine atrogene, la diminution de la mysostatine 2b, la diminution de l’expression de Akt sont en faveur d’une augmentation de la degradation proteique et l’atrophie musculaire apres 2 mois de regimes hypocaloriques. Ces changements s’associent a des differences de composition du microbiote et de la concentration d’AGCC.

introduction Eating in response to specific emotional cues was hitherto investigated in relation to weight gain, eating disorders, and psychiatric and addictive disorders. Given the difficulties in treating established obesity, preventive interventions towards normal-weight subjects could be more appropriate and cost effective. In order to design such interventions, it is important to characterize emotional overeating in normal-weight subjects, especially young women. Methods Female university students aged 18–24 years with healthy Body Mass Index (comprised between 18.5 and 24.9) were asked to complete questionnaires while attending a medical consultation. Emotional Eating frequency in the last 28 days was assessed together with data on habitual physical activity, drinking patterns, substance abuse, suspected eating disorders and cognitive/behavioural components of eating. Sociodemographic data and tobacco use were also collected. Results Half of participants reported intermittent Emotional Overeating in the last 28 days, mostly during one to five days in the last 28 days, in response to Anxiety (51.3%), Loneliness (45.1%), Sadness (44.8%), and Happiness (43.6%), and to a lesser extent in response to Tiredness (27.4%) and Anger (14.6%). In multivariate analysis, Distress-Induced Overeating (DIO) correlated positively with inability to resist emotional cues, disordered eating symptoms, and loss of control over food intake. It correlated negatively with moderate and excessive drinking. Conclusion A large proportion of normal-weight female students used intermittent overeating episodes as a time-limited response to emotional states, especially anxiety. DIO was negatively correlated with alcohol use, which suggests two distinct and somewhat exclusive ways of coping with negative emotions. It was higher in the minority of students with disordered eating symptoms and loss of control over food intake, highlighting the need for a systematic screening in all female students entering college.

International audience; Rationale: Obesity is pandemic. Eating disorders is one of the causative factors. Obesity surgery offers better long-term outcomes than standard medical therapy. Nevertheless, about 20 to 30% of operated obese patients regain weight. That could be explained in many instances by an insufficient management of preoperative eating disorders including FA. The prevalence of FA is not known in obese patients eligible for obesity surgery. The main aim is to identify the prevalence of FA in a cohort of obese patients eligible for obesity surgery.Methods: FA was diagnosed by the validated questionnaire YFAS 2.0. 246 questionnaires were retrospectively analyzed. Each patient consulting in our centre between June 2016 and March 2018 systematically filled out the YFAS 2.0. FA was classified as absence, low, moderate or severe, according to the recommended questionnaire interpretation.Results: Among 246 patients, mean age was 42.5 years old (+/- 13.6), 195 were women (79%). 131 patients (53%) did not have FA. 67 (27%) patients had FA (mean age, 39.3±12.0 yrs; women, n=60 (90%)). Among the 67 patients who had a FA, 6 (9%) had low FA, 22 (33%) moderate FA, and 39 (58%) severe FA. 48 (20%) were not classified because of questionnaires that were partially filled in. At ESPEN congress, more data regarding patients’ profile, including obesity-related complications, will be reported.Conclusions: FA is reported in one third of obese patients referred for obesity surgery. Our study highlighted that many patients did not fill totally the questionnaire, and the subjectivity of the results obtained from a declarative questionnaire. This reinforces the idea that objective criteria, e.g. brain functional magnetic resonance imaging, are needed to diagnose FA and best orientate obese patients’ therapy.

This study investigated the effect of feed supplementation in sows and/or their progeny with 2 sensory feed additives (FA1: limonene and cinnamaldehyde; FA2: menthol, carvone, and anethole) on sows' feed intake, body weight, fat deposition, and colostrum/milk composition, as well as piglets' feed intake growth and feed efficiency from birth to slaughter at postnatal day 160 (PND160). During the last third of gestation and the whole of lactation, sows were subjected to a control diet (C) or the same diet containing FA1 or FA2 at 0.1% of complete feed content. Colostrum/milk samples were taken at days 1, 14, and 28 of lactation for gas chromatography-mass spectrometry analyses. After weaning, the progeny was subjected to a control diet (C) or experimental diets with a sweetener (0.015%) but no other additive (S), or to diets with a sweetener and the additive FA1 (FA1S) or FA2 (FA2S). There was no effect of dietary treatment on sows' feed intake, body weight, or adiposity (P > 0.15 for all), but the sensory characteristics of their colostrum/milk were modified by the diet and diet*time interaction. Limonene concentrations were higher in FA1 samples from PND1 to PND28, whereas carvone and anethole concentrations were higher in FA2 samples from PND1 to PND28. The concentration of these 3 compounds increased with time in the respective groups where they were mostly detected. Menthol concentrations were higher in FA2 samples at PND14 and PND28, but there was no time effect. Overall, cinnamaldehyde was always below the detection range. Piglets born from FA1 and FA2 sows had higher body weight (P = 0.034 at PND160), average daily gain (ADG; P = 0.036 for PND0-160), and average daily feed intake (ADFI; P = 0.006 for PND28-160) than piglets born from C sows. Overall, piglets that were never exposed to FA or only after weaning had lower ADG (P = 0.030 for PND0-160) and ADFI (P = 0.016 for PND28-160) than piglets that were exposed to FA only via the maternal diet, the condition combining both pre- and post-natal exposure being intermediary. In conclusion, FA1 and FA2 provided to gestating and lactating sows increased the progeny's feed intake and growth, suggesting nutritional programming and/or sensory conditioning during the perinatal period. Addition of FA only in the progeny's diet was not beneficial.

National audience

Butyrate can improve gut functions, whereas histone deacetylase inhibitors might alleviate neurocognitive alterations. Our aim was to assess whether oral butyrate could modulate brain metabolism and plasticity and if this would relate to gut function. Sixteen pigs were subjected to sodium butyrate (SB) supplementation via beverage water or water only [control (C)]. All pigs had blood sampled after 2 and 3 wk of treatment, and were subjected to a brain positron emission tomography after 3 wk. Animals were euthanized after 4 wk to sample pancreas, intestine, and brain for gut physiology and anatomy measurements, as well as hippocampal histology, Ki67, and doublecortin (DCX) immunohistochemistry. SB compared with C treatment triggered basal brain glucose metabolism changes in the nucleus accumbens and hippocampus ( P = 0.003), increased hippocampal granular cell layer volume ( P = 0.006), and neurogenesis (Ki67: P = 0.026; DCX: P = 0.029). After 2 wk of treatment, plasma levels of glucose, insulin, lactate, glucagon-like peptide 1, and peptide tyrosine tyrosine remained unchanged. After 3 wk, plasma levels of lactate were lower in SB compared with C animals ( P = 0.028), with no difference for glucose and insulin. Butyrate intake impacted very little gut anatomy and function. These results demonstrate that oral SB impacted brain functions with little effects on the gut.-Val-Laillet, D., Guérin, S., Coquery, N., Nogret, I., Formal, M., Romé, V., Le Normand, L., Meurice, P., Randuineau, G., Guilloteau, P., Malbert, C.-H., Parnet, P., Lallès, J.-P., Segain, J.-P. Oral sodium butyrate impacts brain metabolism and hippocampal neurogenesis, with limited effects on gut anatomy and function in pigs.

Functional, molecular and genetic neuroimaging has highlighted the existence of brain anomalies and neural vulnerability factors related to obesity and eating disorders such as binge eating or anorexia nervosa. In particular, decreased basal metabolism in the prefrontal cortex and striatum as well as dopaminergic alterations have been described in obese subjects, in parallel with increased activation of reward brain areas in response to palatable food cues. Elevated reward region responsivity may trigger food craving and predict future weight gain. This opens the way to prevention studies using functional and molecular neuroimaging to perform early diagnostics and to phenotype subjects at risk by exploring different neurobehavioral dimensions of the food choices and motivation processes. In the first part of this review, advantages and limitations of neuroimaging techniques, such as functional magnetic resonance imaging (fMRI), positron emission tomography (PET), single photon emission computed tomography (SPECT), pharmacogenetic fMRI and functional near-infrared spectroscopy (fNIRS) will be discussed in the context of recent work dealing with eating behavior, with a particular focus on obesity. In the second part of the review, non-invasive strategies to modulate food-related brain processes and functions will be presented. At the leading edge of non-invasive brain-based technologies is real-time fMRI (rtfMRI) neurofeedback, which is a powerful tool to better understand the complexity of human brain–behavior relationships. rtfMRI, alone or when combined with other techniques and tools such as EEG and cognitive therapy, could be used to alter neural plasticity and learned behavior to optimize and/or restore healthy cognition and eating behavior. Other promising non-invasive neuromodulation approaches being explored are repetitive transcranial magnetic stimulation (rTMS) and transcranial direct-current stimulation (tDCS). Converging evidence points at the value of these non-invasive neuromodulation strategies to study basic mechanisms underlying eating behavior and to treat its disorders. Both of these approaches will be compared in light of recent work in this field, while addressing technical and practical questions. The third part of this review will be dedicated to invasive neuromodulation strategies, such as vagus nerve stimulation (VNS) and deep brain stimulation (DBS). In combination with neuroimaging approaches, these techniques are promising experimental tools to unravel the intricate relationships between homeostatic and hedonic brain circuits. Their potential as additional therapeutic tools to combat pharmacorefractory morbid obesity or acute eating disorders will be discussed, in terms of technical challenges, applicability and ethics. In a general discussion, we will put the brain at the core of fundamental research, prevention and therapy in the context of obesity and eating disorders. First, we will discuss the possibility to identify new biological markers of brain functions. Second, we will highlight the potential of neuroimaging and neuromodulation in individualized medicine. Third, we will introduce the ethical questions that are concomitant to the emergence of new neuromodulation therapies., Highlights • We review the neural vulnerability factors related to obesity and eating disorders. • We compare the pros and cons of neuroimaging techniques to study eating behavior. • We present non-invasive strategies to modulate food-related brain processes. • We also present invasive neuromodulation methods such as VNS and DBS. • We discuss about neuroimaging and neuromodulation for prevention and therapy.

Our study aimed at investigating the effect of feed supplementation, from weaning, with 3 sensory feed additives (FA1, FA2, and FA3) on feed preferences, feed intake, and growth of piglets. The FA1 contained extract of Stevia rebaudiana (10 to 20%), extract of high-saponin plants (5 to 10%), and excipients (70 to 85%), the FA2 was mainly composed of a natural extract of Citrus sinensis (60 to 80%), and the FA3 was made of a blend of extracts of hot-flavored spices (5 to 15%) and excipients (85 to 95%). At weaning (d 1), a total of 32 female piglets housed in individual pens were allocated to 4 treatments (FA1, FA2, FA3, and control [CON]) of equivalent mean weight. The pigs were fed a standard pelleted prestarter diet from weaning (d 1) to d 15 and a starter diet from d 16 to 28. The diets were supplemented with the feed additives (FA) corresponding to their treatment, while the CON treatment was the standard diets with no additive. Feed refusals were weighed daily and piglets were weighed weekly on d 1, 7, 14, 21, and 28. On the day of feed transition (d 16) as well as 7 (d 23) and 10 d (d 26) later, the animals were consecutively subjected to 1- and 22-h double-choice feeding tests to investigate their preferences during a short period and a longer period of time for the CON starter diet and the starter diet added with the FA corresponding to their treatment. No overall effect of the feed additives was observed on ADFI, ADG, G:F, and final BW. No overall preference was highlighted for the FA1 treatment, except for a preference for the FA1 starter diet during the 1-h test on d 23 (78% of total feed intake; P < 0.01). For the FA2 treatment, the pigs consumed the FA2 starter diet more than the CON starter diet during the 22-h tests on d 16 (67% of total feed intake; P < 0.05) and 26 (62% of total feed intake; P < 0.01). For the FA3 treatment, on d 26, the FA3 starter diet was and tended to be consumed more than the CON starter diet during 1- (69% of total intake; P < 0.05) and 22-h (60% of total intake; P < 0.10) tests, respectively. In conclusion, feed supplementation with the FA1, FA2, and FA3 from weaning did not induce beneficial effects on feed intake and growth performance during the early postweaning period. The FA2 increased palatability and acceptance of the unfamiliar starter diet the day of feed transition, while the FA1 and FA3 increased palatability of the starter diet only after a few days of exposure, most likely through long-term familiarization processes.