BACKGROUND:Although semaglutide 2.4 mg has demonstrated significant weight loss efficacy in clinical trials, real-world data, particularly with regard to clinically complex and underrepresented populations, remain limited. OBJECTIVES:The study aims to assess the real-world effectiveness and patient-reported outcomes associated with the use of semaglutide 2.4 mg in individuals with severe and complex obesity. The study also intends to characterize weight loss response in pre-defined subgroups of patients and to identify predictors of weight loss using machine learning. METHODS:SEMASEARCH is a retrospective multicentric observational cohort embedded within the French early-access program for semaglutide 2.4 mg. A total of 1100 patients with severe obesity (BMI ≥ 40 kg/m2 with at least one treated obesity-related complication) were retrospectively included from 11 expert obesity centers, based on prospectively collected data at baseline, 6 months, and 12 months. Subgroups include patients with a history of bariatric surgery, binge eating disorder, hypothalamic obesity, age ≥ 60 years or altered body composition, BMI ≥ 60 kg/m2, and those receiving psychotropic medications. Assessments include clinical, biological, and body composition data, as well as standardized questionnaires evaluating eating behaviour, physical activity, sleep, quality of life, digestive symptoms, and mental health. PRIMARY OUTCOME:Body weight change since treatment initiation, with assessment at 6 and 12 months. SECONDARY OUTCOMES:Clinically meaningful weight loss (≥ 10%) at 12 months, metabolic improvements, patient-reported outcomes, body composition changes, and tolerance. EXPECTED IMPACT:SEMASEARCH will provide real-world evidence on Semaglutide 2.4 mg use in patients living with severe and complex obesity. It will also address major knowledge gaps in specific populations underrepresented in clinical trials and generate predictive models of weight loss response.

BACKGROUND:Factors influencing fetal growth after metabolic bariatric surgery remain to be clarified. OBJECTIVES:To evaluate the relationships between birth weight (BW) and maternal nutritional and metabolic parameters after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). SETTING:University Hospital, France. METHODS:Women with a singleton pregnancy who underwent at least one second-trimester nutritional assessment at our institution between 2006 and 2022 were included. Associations between maternal parameters and BW adjusted for sex and gestational age (Z-score) were studied. RESULTS:A total of 155 pregnancies were studied, 71 after RYGB and 84 after SG. Although postoperative weight loss was greater after RYGB, maternal characteristics before pregnancy were comparable. The number of nutritional deficiencies was similar but women after RYGB took more nutritional supplements, while gestational weight gain was greater after SG. Mean BW (3095 ± 628 g versus 3184 ± 516 g) and the proportion of small-for-gestational-age (SGA) newborns (24% versus 21%) were similar between procedures. No association was observed between nutritional deficits and BW. After RYGB, serum iron parameters were negatively correlated with BW Z-score, while fasting glucose and insulin concentrations were positively correlated (P < .01). No significant associations were identified after SG. CONCLUSIONS:Despite a similar risk of SGA, the maternal determinants of BW differ between RYGB and SG. Metabolic parameters appear to be involved after RYGB but not after SG, whereas nutritional deficiencies do not seem to be associated with BW. Additional maternal factors, particularly after SG, should be investigated to explain the increased risk of SGA.

OBJECTIVE:Fat taste sensitivity has been implicated in long-term weight loss after bariatric surgery. Unexpectedly, improvement of orosensory fat acuity was not systematic in operated patients. METHODS:Obesity-induced alterations of gene expression in gustatory papillae having been recently reported, we have explored the fungiform transcriptomic activity in the bariatric surgery context. Fat taste detection thresholds (three-alternative ascending forced-choice tests) alongside transcriptomic profiling of freshly isolated fungiform papillae were assessed in women with severe obesity before and 6 months after sleeve gastrectomy. RESULTS:According to evolution of post surgery detection thresholds, lipid-improved and -unimproved subgroups were identified, despite similar initial anthropometric parameters. Lower weight loss and higher plasma fasting insulin, C-reactive protein, and fibrinogen levels distinguished lipid-unimproved patients. This subgroup also overexpressed genes involved in inflammation and apoptosis, with certain ones being positively correlated with high lipid detection thresholds (low sensitivity), whereas the key gene of taste bud cell signaling, TRPM5, was down-expressed. In lipid-improved patients, genes implicated in cell renewal, neuronal function, and receptor recycling were upregulated and associated with better lipid detection efficiency. Pathway enrichment identified immune and anti-inflammatory activities in lipid-unimproved and -improved groups, respectively. CONCLUSIONS:These findings collectively suggest that changes in gene expression within gustatory papillae contribute to fat taste sensitivity after sleeve gastrectomy.

BACKGROUND:Incisional hernia repairs (IHRs) are not recommended in patients with severe obesity (BMI ≥ 35 kg/m2). Weight loss is challenging, but new medications, such as glucagon-like peptide-1 receptor agonists (GLP-1 agonists), have recently attracted increased attention for their potential weight loss advantages. The aim was to analyze the preliminary results about the safety and weight loss efficiency of the use of GLP-1 agonists in the context of prehabilitation prior to complex IHR. METHODS:All patients planned for IHR with a BMI ≥ 35 kg/m2 and treated with preoperative GLP-1 agonists were included in the experimental group and compared with a comparable historical surgical cohort treated with a conventional tailored nutritional preoperative management. Weight loss in the experimental group and perioperative and postoperative outcomes were compared between the two groups. The success rate of GLP1 agonists was defined as a weight loss that enables the patient to fall within the recommended limits of a BMI ≤ 35 kg/m2 before an IHR. RESULTS:Fifty-two patients in the control group were compared to 24 with GLP-1 agonists. The distribution of GLP-1 agonists was as follows: semaglutide (n = 12; 50%), dulaglutide (n = 7; 29.2%), and liraglutide (n = 5; 20.8%). The mean initial BMI was 40.1 ± 3.6 kg/m2 kg/m2. The average percentage of weight loss was 11.3 ± 7.4% with GLP-1 agonists (maximum weight loss was observed with semaglutide 2.4 mg/wk). The success rate of GLP1 agonists (defined as BMI ≤ 35 kg/m2 before IHR) was reached for 15/24 patients (62.5%). Postoperative total complication rate was lower in the group with GLP-1 agonists (59.6% in the control group vs. 45.8% in GLP-1 and p = 0.2). CONCLUSION:This study demonstrated the efficacy of GLP-1 agonists in the optimization of patients with obesity, allowing two thirds of the patients to benefit from IHR, with a tendency for lower morbidity. TRIAL REGISTRATION:CPP Mediterranee, n° 21.00430.000004.

BACKGROUND AND AIM:Gut hormones such as GLP-1 and PYY increase after bariatric surgery. However, implication of endogenous gut hormones in weight loss (WL) after surgery remains unclear. Our study aimed at objectifying the role of gut hormones in postoperative WL in 32 women with obesity who underwent vertical sleeve gastrectomy (VSG). METHODS:Post-meal tests were realized to measure plasma gut hormones (GLP-1, PYY and ghrelin), before and 6 months after VSG. Area under the curve and peak/basis ratios (T30/T0) were analyzed for each hormone in relation to percentage WL (%WL) and caloric intake decrease (%CID) evaluated at 6, 12, 36 months after surgery. RESULTS:Fasting GLP-1 and PYY secretions were not altered by surgery but their postprandial peaks were significantly elevated. Fasting and postprandial Ghrelin secretions were drastically reduced. Preoperative ghrelin was negatively correlated with 6 months %CID. Preoperative peak/basis ratio of PYY and GLP-1 were both negatively correlated with postoperative %WL at 36 months (P < 0,01 and P < 0,05). Post/preoperative peak ratios of PYY secretion were positively correlated to %WL from 6 months to 36 months after VSG (P < 0,05). Finally, receiver operating characteristic (ROC) curve analyses show that preoperative peak/basis PYY or GLP-1 and post/preoperative peak ratios of PYY were able to predict long-term efficiency of VSG defined as %WL ≥ 30 % at 36 months. CONCLUSION:Preoperative postprandial secretion of PYY and its ability to increase early after surgery is predictive of long-term WL after VSG. This study emphasizes the importance of postprandial gut hormone assessment to improve the operated patient's personalized care.

BACKGROUND:Nutritional deficiencies are frequent after metabolic and bariatric surgery (MBS) and systematic addition of vitamin B12, iron, calcium, and vitamin D to standard multivitamin tablets is recommended. However, there are still uncertainties because supporting data are few and compliance with a large number of tablets is low. OBJECTIVES:To assess the need for additional supplements using a supplementation based on biological assays after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). METHODS:Consecutive patients (N = 313: 179 RYGB/134 SG; 86% women, mean age 44.1 ± 10.3 years, Body mass index 43.5 ± 6.6 kg/m2) who underwent a nutritional assessment, before and at 6, 12, and 36 months after MBS, were studied. Multivitamin tablets were systematically prescribed after MBS, and additional supplements were introduced following a standardized protocol in the case of deficiency. SETTING:University Hospital, France. RESULTS:Although the number of patients taking additional supplements increased by more after RYGB than after SG (58.7% vs 43.3%, P < .01), the mean number of deficits did not increase and was similar at 3 years (3.7 vs 3.4, Ns). The frequency of nutritional symptoms was also similar after both procedures, the most common being hair loss, while neurological symptoms were unusual and mild. Anemia was infrequent, but secondary hyperparathyroidism was frequent after RYGB (23% vs 9% after SG, P < .01). CONCLUSIONS:A personalized supplementation strategy adapted to biological parameters, in patients followed regularly up to 3 years after MBS, may reduce the number of nutritional supplements without increasing the number of deficiencies. However, vigilance must be maintained, particularly regarding bone and neurological risks.

Context: The association of obesity with bone fragility fractures is complex and non-linear. Despite good efficacy on weight loss, bariatric surgery (BS) is also associated with bone loss. However, we lack information on risk factors of the long-term deleterious effects of BS on the skeleton. Objective: We aimed to assess the factors associated with low bone mineral density (BMD) performed a long time after Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG). Methods: This cross-sectional study involved patients at a long distance from their BS that underwent dual-energy x-ray absorptiometry (DXA) with biological factors (vitamins, micronutrients, bone and inflammation biomarkers). Simple and multiple linear models (stepwise and parsimony approach) were developed. Results: A total of 131 patients (91 RYGB, 40 SG) underwent DXA (51.8 +/- 11.08 years, 87.8% women). At a mean of 6.8 +/- 3.7 years after surgery, the mean weight loss was -28.6 +/- 9.6%, and only 6 patients (5.7%) had a T-score less than or equal to 2.5. On univariate analysis, BMD was lower in the RYGB than in the SG group (P < .001) at all sites, despite similar fat and fat-free mass and weight loss. Serum parathyroid hormone and phosphate levels were higher in RYGB than SG patients. A total of 10.1% of patients showed vascular calcifications. On multivariable analysis, BMD remained different between surgery groups after adjustment for age, body mass index, ethnicity, and sex. The model-adjusted R2 values were 0.451 for the total hip; 0.462 the femoral neck, and 0.191 the lumbar spine for the inflammation model; 0.458, 0.462, and 0.254, respectively, for the bone marker model; and 0.372, 0.396, and 0.142 for the vitamin model. Serum zinc, ferritin, and uric acid levels were the markers associated with BMD to a low extent. Conclusion: BMD differed depending on the BS procedure. A few biological markers may be associated weakly with BMD well after the surgery.

ObjectiveBariatric surgery has an impact on subsequent pregnancies, in particular an association between gastric bypass and small for gestational age. Knowledge is lacking on whether sleeve gastrectomy is associated with more favorable pregnancy outcomes. This study aimed to compare the impact of sleeve gastrectomy and Roux-en-Y gastric bypass on the incidence of small for gestational age (SGA), and of adverse pregnancy outcomes.Study designWe conducted a retrospective study in a single reference center, including all patients with a history of sleeve or bypass who delivered between 2004 and 2021 after their first pregnancy following bariatric surgery. We compared the incidence of SGA, intrauterine growth retardation, preterm delivery and adverse maternal outcomes between patients who had sleeve versus bypass.ResultsOf 244 patients, 145 had a sleeve and 99 had a bypass. The proportion of SGA <10th percentile did not differ between the two groups (38/145 (26.2%) vs 22/99 (22.22%), respectively, p=0.48). Preterm birth < 37 WG was lower in the sleeve group (5/145 (3.45%) vs 12/99 (12.12%) in the bypass group (p=0.01), as well as NICU hospitalizations (3 (2.07%) vs 12/99 (12.12%), p<0.01). There was no difference regarding adverse maternal outcomes such as gestational diabetes and hypertensive complications. The proportion of SGA was not lower in patients with bypass when adjusting for other risk factors (BMI, smoking, geographic origin, diabetes and hypertension) (aOR 0.70; 95%CI 0.01 – 2.85).Conclusionsleeve was associated with an incidence of SGA which was as high as after bypass, however the incidence of preterm birth was lower.

The main concerns following sleeve gastrectomy (SG) include the risk of gastroesophageal reflux disease (GERD) and its complications, such as Barrett’s esophagus (BE). However, there is conflicting data on esophageal conditions, and studies on alterations of gastric mucosa after SG are lacking, despite reported cases of gastric cancer. Our aim was to assess esophageal and gastric lesions after SG. From November 2017, an upper gastrointestinal endoscopy (UGE) was proposed at least 3 years after SG to all patients operated on in our institution. Endoscopic results and gastric histological findings were analyzed. BE was defined as endoscopically suspected esophageal metaplasia with histological intestinal metaplasia. Between September 2008 and August 2018, 375 patients underwent SG at our institution, of which 162 (43

Senescence is a key event in the impairment of adipose tissue (AT) function with obesity and aging but the underlying molecular and cellular players remain to be fully defined, particularly with respect to the human AT progenitors. We have found distinct profiles of senescent progenitors based on AT location between stroma from visceral versus subcutaneous AT. In addition to flow cytometry, we characterized the location differences with transcriptomic and proteomic approaches, uncovering the genes and developmental pathways that are underlying replicative senescence. We identified key components to include INBHA as well as SFRP4 and GREM1, antagonists for the WNT and BMP pathways, in the senescence-associated secretory phenotype and NOTCH3 in the senescence-associated intrinsic phenotype. Notch activation in AT progenitors inhibits adipogenesis and promotes myofibrogenesis independently of TGFβ. In addition, we demonstrate that NOTCH3 is enriched in the premyofibroblast progenitor subset, which preferentially accumulates in the visceral AT of patients with an early obesity trajectory. Herein, we reveal that NOTCH3 plays a role in the balance of progenitor fate determination preferring myofibrogenesis at the expense of adipogenesis. Progenitor NOTCH3 may constitute a tool to monitor replicative senescence and to limit AT dysfunction in obesity and aging.

Sleeve gastrectomy (SG) often induces gastroesophageal reflux, with few and discordant long-term data on the risk of Barrett's esophagus (BE) in operated patients. The aim of this study was to analyze the impact of SG on esogastric mucosa in a rat model at 24 weeks postoperatively, which corresponds to approximately 18 years in humans. After 3 months of a high-fat diet, obese male Wistar rats were subjected to SG (n = 7) or sham surgery (n = 9). Esophageal and gastric bile acid (BA) concentrations were measured at sacrifice, at 24 weeks postoperatively. Esophageal and gastric tissues were analyzed by routine histology. The esophageal mucosa of the SG rats (n = 6) was not significantly different in comparison to that of the sham rats (n = 8), with no esophagitis or BE. However, there was more antral and fundic foveolar hyperplasia in the mucosa of the residual stomach 24 weeks after SG than in the sham group (p < 0.001). Luminal esogastric BA concentrations did not differ between the two groups. In our study, SG induced gastric foveolar hyperplasia but no esophageal lesions at 24 weeks postoperatively in obese rats. Therefore, long-term endoscopic esophageal follow-up that is recommended in humans after SG to detect BE may also be useful for detecting gastric lesions.

This guide describes the care, support and overall follow-up of adults with overweight or obesity. It reasserts the importance of early identification, coupled with a lifestyle assessment. It details the role of professionals (health, social and medico-social field, adapted physical activity, occupational health) and looks at the situations in which the person's primary care physician may consult them. This work was conducted jointly with the French national health insurance fund, in the context of the healthcare system transformation strategy, to meet the objectives of the "Ma sante 2022" ["My Health 2022"] program. It was produced with the assistance of a multidisciplinary working group and patient association representatives drawing on an analysis on the international literature. To help professionals assimilate this work, the HAS proposes a summary of the critical points in the care pathway, 14 key messages to improve practices, 8 toolkit guides reiterating the role of each professional and the arrangements for sharing information with the primary care physician. (c) 2023 Societe francophone nutrition clinique et metabolisme (SFNCM). Published by Elsevier Masson SAS. All rights reserved.

Le guide du parcours de soins « Surpoids et obésité de l'adulte » publié par la Haute Autorité de Santé (HAS) en 2023 décrit les soins, l'accompagnement et le suivi global de l'adulte en situation de surpoids ou d'obésité. Il réaffirme l'importance d'un dépistage précoce couplé à une évaluation des habitudes de vie. Il détaille le rôle des professionnels (santé, champ social et médico-social, activité physique adaptée, santé au travail) et revient sur les situations dans lesquelles le médecin traitant peut les solliciter. En plus, le guide indique aux professionnels des démarches pour délivrer des soins et un accompagnement à des populations spécifiques : les personnes en situation de handicap et les femmes en situation d'obésité. Ces travaux ont été menés en copilotage avec la Caisse nationale d'assurance maladie, dans le cadre de la stratégie de transformation du système de santé, pour répondre aux objectifs de « Ma santé 2022 ». Ils ont été construits avec un groupe de travail pluriprofessionnel et des représentants des associations de patients, à partir d'une analyse de la littérature internationale. Pour permettre aux professionnels de s'approprier ces travaux, la HAS propose en plus du guide de parcours, une synthèse sur les points critiques du parcours de soins, 14 messages clés pour améliorer les pratiques présentés dans cet article, et 8 fiches rappelant le rôle de chaque professionnel impliqué dans le parcours et les modalités de partage d'informations avec le médecin traitant. © 2023 Société francophone nutrition clinique et métabolisme (SFNCM). Publié par Elsevier Masson SAS. Tous droits réservés. This guide describes the care, support and overall follow-up of adults with overweight or obesity. It reasserts the importance of early identification, coupled with a lifestyle assessment. It details the role of professionals (health, social and medico-social field, adapted physical activity, occupational health) and looks at the situations in which the person's primary care physician may consult them. This work was conducted jointly with the French national health insurance fund, in the context of the healthcare system transformation strategy, to meet the objectives of the "Ma santé 2022" ["My Health 2022"] program. It was produced with the assistance of a multidisciplinary working group and patient association representatives drawing on an analysis on the international literature. To help professionals assimilate this work, the HAS proposes a summary of the critical points in the care pathway, 14 key messages to improve practices, 8 toolkit guides reiterating the role of each professional and the arrangements for sharing information with the primary care physician. © 2023 Société francophone nutrition clinique et métabolisme (SFNCM). Published by Elsevier Masson SAS. All rights reserved.

L'obésité induit une inflammation chronique et systémique de bas grade qui impliquerait le système immunitaire intestinal. En effet, au cours d'un régime riche en graisses, l'interaction du tractus intestinal avec les aliments et le microbiote favorise, dans l'intestin grêle, une inflammation précoce — avant l'apparition de l'obésité — qui contribue au développement de cette obésité. Nous posons l'hypothèse selon laquelle les cellules immunitaires, comme les cellules épithéliales intestinales, s'adaptent au nouvel environnement nutritionnel de l'intestin restructuré par la chirurgie bariatrique et contribuent aux effets bénéfiques de celle-ci. L'objectif de ce travail était de quantifier et phénotyper, chez des patients atteints d'obésité ou antérieurement opérés d'un bypass gastrique de type Roux-en-Y (RYGB), les différentes populations de cellules immunitaires intestinales. Des fragments de jéjunum de patients obèses candidats à une première chirurgie bariatrique (CTRL-OB) ou en conversion pour échec pondéral ou complication tardive d'une première chirurgie de type RYGB ont été collectés (Cohorte prospective COBILOM, NCT03538210). Des analyses histologiques (HPS et PAS + BA) et immunohistochimiques ont été réalisées avec des anticorps primaires spécifiques de CD45 (leucocytes totaux), CD4 (lymphocytes T helper), CD8 (lymphocytes T cytotoxiques) et CD20 (lymphocytes B) (n = 10 par groupe). Les lames ont été scannées puis le marquage a été quantifié sur 10 villosités jéjunales par coupe en utilisant le logiciel Calopix®. Les résultats ont été exprimés en pourcentage de surface marqué sur la surface totale de la villosité. Les lymphocytes intra-épithéliaux (IEL) et les lymphocytes de la lamina propria (LPL) ont été isolés à partir de muqueuse jéjunale, puis marqués par des anticorps fluorescents ciblant des antigènes spécifiques de surface (CD45, CD3, TCRγδ, CD8, CD4, CD8β, CD127, KLRG1, CD103, CD161), et analysés par FACS afin de les phénotyper. Les résultats ont été analysés avec le FlowJo. Sur les coupes histologiques de jéjunum, nous observons une augmentation significative de la hauteur de la muqueuse jéjunale et des villosités chez les patients opérés de RYGB par rapport aux patients obèses non opérés (p < 0,05). Le nombre de leucocytes totaux (CD45+) était diminué de 40 % dans la muqueuse jéjunale des patients RYGB (p < 0,01 vs CTRL-OB). Le nombre de lymphocytes CD8+ était également diminué et cette réduction était plus importante pour les IEL CD8+ que pour les LPL CD8+ (−77 %, p < 0,01 vs CTRL-OB). L'analyse des lymphocytes intestinaux de patients non opérés par FACS indique que le nombre de LT CD8αβ+ était plus élevé que le nombre de LT CD8αα+. Pour les résultats de cytométrie de flux, nous observons après chirurgie de type RYGB une tendance à la diminution du ratio TCRαβ/TCRγδ, du ratio CD8/CD4 parmi les TCRαβ et du ratio CD8αβ/CD8αα ce qui indiquerait une diminution des cellules connues comme étant pro-inflammatoires par rapport à celles connues comme anti-inflammatoires. Cependant, le nombre de patient n'est pas encore assez important pour pouvoir conclure définitivement sur ces résultats. Le remodelage de l'intestin par le RYGB induit une hypertrophie de la muqueuse jéjunale, associée à une diminution de la population de lymphocytes T CD8+ intestinaux, et en particulier des IEL pro-inflammatoires.

Introduction A 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. Methods Thirty-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. Results VSG 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. Conclusion Collectively, 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.

La chirurgie bariatrique (CB) est le traitement le plus efficace de l'obésité sévère à long terme. Cependant, l'importante variabilité inter-individuelle de la perte de poids (PP) et de la correction des désordres métaboliques après la chirurgie est incomplètement expliquée et très peu de données ont été publiées concernant l'influence de la cellularité du tissu adipeux. Notre objectif était donc d'explorer la relation entre la cellularité initiale des dépôts de graisse sous-cutanée (SAT) et viscérale (VAT), la PP et l'insulinorésistance (IR) après CB. Cent soixante et un sujets obèses sévères (IMC moyen 44 ± 6 kg/m2, âge 42 ± 11 ans, 14 % d'hommes, 71 % de Roux-en-Y bypass gastrique) ont été inclus dans l'étude (cohorte SENADIP, ClinicalTrials.gov Identifier : NCT01525472). Des échantillons de SAT et de VAT ont été prélevés pendant la chirurgie. Après digestion enzymatique, le diamètre des adipocytes et le nombre de sous-types de progéniteurs et de cellules immunitaires ont été déterminés. L'évolution des paramètres anthropométriques et métaboliques a été étudiée à 1 an (n = 153) et 3 ans (n = 78) après la CB. L'efficacité de la CB, en termes de perte de PP et de correction de l'IR, était associée à des compartiments cellulaires distincts selon le dépôt de graisse étudié. Une faible corrélation positive était observée entre l'IMC préopératoire, le nombre de progéniteurs adipogéniques (MSCA1+) et la taille des adipocytes principalement dans le SAT. En revanche, la perte de poids à 3 ans après CB était négativement associée au nombre initial de progéniteurs MSCA1+ et aux différents sous-types de lymphocytes dans le SAT, alors qu'elle était associée à la proportion de gros adipocytes matures dans le VAT. L'IR préopératoire était essentiellement associée au nombre de cellules MSCA1+ et de lymphocytes T dans le SAT, alors qu'elle était associée à la proportion de gros adipocytes et au nombre de macrophages dans le VAT. Ces caractéristiques initiales du tissu adipeux étaient également des prédicteurs négatifs de l'amélioration de l'IR à 3 ans de la CB. Enfin, le nombre de progéniteurs myofibrogéniques (−/CD271+) des 2 dépôts était déterminant pour la trajectoire pondérale des patients entre 1 an et 3 ans après la CB. Les caractéristiques du tissu adipeux en termes de taille des adipocytes, de sous-types de progéniteurs et de cellules immunitaires sont déterminantes dans les altérations métaboliques associées à l'obésité. De plus, les marqueurs de remodelage du tissu adipeux dans le SAT, ainsi que l'hypertrophie des adipocytes dans le VAT, sont tous deux prédictifs des résultats de la CB, en terme de PP et d'amélioration de l'IR, suggérant que la balance inter-dépôt entre l'hypertrophie et l'hyperplasie est un déterminant majeur de la santé métabolique.

L'ostéoporose est fréquente, sous diagnostiquée et prédispose aux fractures de fragilité. L'obésité ouvre de nouveaux défis avec une relation complexe, non linéaire avec la fragilité osseuse. La chirurgie bariatrique s'est démocratisée avec d'importants effets sur la perte de poids. Les effets osseux à long terme restent faiblement décrits. Notre objectif est d'évaluer les déterminants de densité osseuse basse lors d'une évaluation à long terme (> 2 ans) entre By-pass gastrique (RYGB) et Sleeve gastrectomie (SG). Nous avons réalisé une étude transversale à partir d'une cohorte de sujets suivis au long cours en chirurgie bariatrique, chez qui nous avons réalisé des mesures de densité minérale osseuse (DMO), de calcification vasculaire et de composition corporelle. À ceci s'ajoute l'évaluation des paramètres biologiques comme potentiels facteurs de risque dont l'étude des vitamines (A, B1, B3, B6, B9, B12, C, D, E), des micronutriments, des marqueurs osseux et d'inflammation. L'étude comparative a utilisé des tests de Student, Mann-Whitney et Anova pour la partie univariée. Analyse multivariée réalisée avec un modèle linéaire multiple. Les tests sont bilatéraux, risque alpha fixé à 5 %. Au total 131 patients dont 91 RYGB et 40 SG ont pu avoir une analyse DXA (51,8 ans, 87,8 % de femmes). Dans cette analyse à long-terme (6,8 ± 3,7 ans de la chirurgie), la perte de poids moyenne était de −28,6 % ± 9,6 % par rapport au poids avant chirurgie. Dans les stades d'obésité sévère (indice de masse corporelle (IMC) > 40 kg/m2), on retrouvait les DMO et les CRP les plus hautes quelle que soit la procédure. En analyse univariée, la DMO était significativement plus basse chez les RYGB à tous les sites (p < 0,001), malgré des compositions corporelles similaires. De plus, les RYGB avaient des concentrations de parathormone et de phosphate plus élevées. Seuls 10,1 % des sujets avaient des calcifications vasculaires qui auraient pu limiter l'interprétation de la DMO au rachis, sans différence entre le type de chirurgie. La DMO à tous les sites était influencée par l'amplitude initiale de la perte de poids, avec un effet plus important chez les SG. Dans l'analyse mutlivariée, le Zinc, la ferritine et l'acide urique sont les seuls marqueurs explicatifs de la DMO retrouvés après ajustement sur l'âge, l'IMC, le sexe et le type de chirurgie. Le modèle était plus fort pour prédire la DMO à la hanche (fémur total et col) qu'au rachis lombaire (R2 ajusté = 0,451 ; 0,462 et 0,191 respectivement). Aucune des vitamines n'était impliqué comme variable explicative de la DMO dans les modèles finaux. Les différences de DMO entre les procédures chirurgicales soulignent des trajectoires différentes à distance de la chirurgie, quel que soit le contrôle des paramètres osseux.

L’obésité réduit la perception oro-sensorielle des lipides alimentaires chez les rongeurs et chez certains sujets, affectant ainsi leurs choix alimentaires. Bien que la chirurgie bariatrique corrige partiellement cette altération, les mécanismes sous-jacents restent mal compris. Pour explorer l’implication potentielle de changements métaboliques dans ce phénomène, une analyse du métabolome plasmatique, un comptage de papilles gustatives fongiformes et des tests comportementaux à double choix ont été réalisés chez des souris rendues obèses par régime hyperlipidique (HFD) et ayant subi soit une sleeve gastrectomie (SG-HFD, n=11) ou une opération à blanc (T-HFD, n=14). Nous avons trouvé que (1) la SG réduit à la fois la signature neurotoxique plasmatique due à la sur-activation de la voie tryptophane/kynurénine (Trp/Kyn) et la dégradation de la préférence spontanée pour les solutions lipidiques observées chez les souris T-HFD, (2) la densité des papilles fongiformes est négativement corrélée avec l’activation de la voie Trp/Kyn et (3) l’inhibition pharmacologique de la synthèse de Kyn reproduit chez des souris obèses non opérées les effets positifs de la SG. Ces données fournissent une explication métabolique inédite à la perturbation du « goût du gras » constatée au cours de l’obésité.