Fate and Complex Pathogenic Effects of Dioxins and Polychlorinated Biphenyls in Obese Subjects before and after Drastic Weight Loss

BACKGROUND: In humans, persistent organic pollutants (POPs) are stored primarily in adipose tissue. Their total body burden and their contribution to obesity-associated diseases remain unclear. OBJECTIVES: We characterized POP total body burden and their redistribution in obese individuals before and after drastic weight loss and compared these values with a variety of molecular, biological, and clinical parameters. METHODS: Seventy-one obese subjects were enrolled and underwent bariatric surgery. Blood and adipose tissue samples were obtained at different times from these individuals as well as from 18 lean women. RESULTS: POP content (17 dioxins/furans and 18 polychlorinated biphenyl congeners) in different adipose tissue territories was similar, allowing us to assess total POP body burden from a single biopsy. Total POP body burden was 2 to 3 times higher in obese than in lean individuals. We also found increased expression of some POP target genes in obese adipose tissue. Drastic weight loss led to increased serum POPs and, within 6-12 months, to a significant 15% decrease in total polychlorinated biphenyl body burden. Importantly, serum POP levels were positively correlated with liver toxicity markers and lipid parameters, independently of age and body mass index. CONCLUSIONS: POP content in adipose tissue and serum correlate with biological markers of obesity-related dysfunctions. Drastic weight loss leads to a redistribution of POPs and to a moderate decrease of their total body burden

Metabolite Profiling Identifies Candidate Markers Reflecting the Clinical Adaptations Associated with Roux-en-Y Gastric Bypass Surgery

Background: Roux-en-Y gastric bypass (RYGB) surgery is associated with weight loss, improved insulin sensitivity and glucose homeostasis, and a reduction in co-morbidities such as diabetes and coronary heart disease. To generate further insight into the numerous metabolic adaptations associated with RYGB surgery, we profiled serum metabolites before and after gastric bypass surgery and integrated metabolite changes with clinical data. Methodology and Principal Findings: Serum metabolites were detected by gas and liquid chromatography-coupled mass spectrometry before, and 3 and 6 months after RYGB in morbidly obese female subjects (n = 14; BMI = 46.261.7). Subjects showed decreases in weight-related parameters and improvements in insulin sensitivity post surgery. The abundance of 48 % (83 of 172) of the measured metabolites changed significantly within the first 3 months post RYGB (p,0.05), including sphingosines, unsaturated fatty acids, and branched chain amino acids. Dividing subjects into obese (n = 9) and obese/ diabetic (n = 5) groups identified 8 metabolites that differed consistently at all time points and whose serum levels changed following RYGB: asparagine, lysophosphatidylcholine (C18:2), nervonic (C24:1) acid, p-Cresol sulfate, lactate, lycopene, glucose, and mannose. Changes in the aforementioned metabolites were integrated with clinical data for body mass index (BMI) and estimates for insulin resistance (HOMA-IR). Of these, nervonic acid was significantly and negatively correlated with HOMA-IR (p = 0.001, R = 20.55)

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Plate-forme d’imagerie préclinique AnimAge du CERMEP

National audienceLe CERMEP (Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire) est un centre d'imagerie in vivomultimodale dédié à la recherche biomédicale fondamentale et clinique. A ce titre, le CERMEP fait partie du Noeud Lyonnais de l’infrastructure nationale France Life Imaging (FLI).La plate-forme d’imagerie préclinique ANIMAGE est un département du CERMEP qui a pour objectif de proposer aux chercheurs académiques ou industriels des méthodes d’imagerie in vivo pour l’exploration anatomique, moléculaire et fonctionnelle du petit animal de laboratoire.En termes d’équipement d’imagerie, ANIMAGE dispose d’une IRM BRUKER BioSpec 7T, d’une caméra TEP/TDM SIEMENS Inveon, d’un scanner SKYSCAN-1076 aux rayons X et d’un échographe VISUALSONICS Vevo 770. Une vingtaine de radiotraceurs TEP sont accessibles grâce à la proximité du département de radiochimie et radiopharmacie du CERMEP. Des explorations autoradiographiques in vitro de ces radiotraceurs sont également possibles sur le site. Tous les imageurs sont équipés d’anesthésie gazeuse, d’un poste de contrôle et de suivi physiologique qui servent d’outils de monitoring des animaux tout au long des expérimentations, ponctuelles ou longitudinales. Une salle de salle de chirurgie est mise à la disposition des expérimentateurs, à proximité immédiate des imageurs. Equipée de deux paillasses, disposant de postes d'anesthésie gazeuse, microscopes, etc., elle permet la préparation des modèles animaux ou des journées de formations. Une animalerie conventionnelle (type A1 avec un niveau de confinement L2) permet d'héberger les animaux pendant la durée du protocole d'imagerie. Ces locaux sont agréés par les services vétérinaires pour cinq espèces animales (porcs, lapins, chats, rats, souris). La structure « Bien-Etre Animal » interne au CERMEP accompagne les investigateurs dans leur demande d’autorisation de projet utilisant des animaux à des fins scientifiques (APAFIS – Comité d’éthique). L’essentiel des applications visées aujourd’hui se situe dans le domaine des neurosciences mais la plateforme est ouverte à d’autres thématiques (oncologie, cardiologie, métabolisme, etc.).Les membres d’ANIMAGE accompagnent les équipes de recherche tout au long du protocole de recherche, selon leurs besoins :- définition de la question biologique/physiopathologique/pharmacologique à laquelle pourra répondre l’imagerie,- adéquation de la modalité d’imagerie et du modèle expérimental,- organisation du protocole expérimental,- préparation du modèle animal,- acquisition des images in vivo,- analyse des images et aide à la valorisation scientifique (rapport, article...)

Plate-forme d’imagerie préclinique AnimAge du CERMEP

National audienceLe CERMEP (Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire) est un centre d'imagerie in vivomultimodale dédié à la recherche biomédicale fondamentale et clinique. A ce titre, le CERMEP fait partie du Noeud Lyonnais de l’infrastructure nationale France Life Imaging (FLI).La plate-forme d’imagerie préclinique ANIMAGE est un département du CERMEP qui a pour objectif de proposer aux chercheurs académiques ou industriels des méthodes d’imagerie in vivo pour l’exploration anatomique, moléculaire et fonctionnelle du petit animal de laboratoire.En termes d’équipement d’imagerie, ANIMAGE dispose d’une IRM BRUKER BioSpec 7T, d’une caméra TEP/TDM SIEMENS Inveon, d’un scanner SKYSCAN-1076 aux rayons X et d’un échographe VISUALSONICS Vevo 770. Une vingtaine de radiotraceurs TEP sont accessibles grâce à la proximité du département de radiochimie et radiopharmacie du CERMEP. Des explorations autoradiographiques in vitro de ces radiotraceurs sont également possibles sur le site. Tous les imageurs sont équipés d’anesthésie gazeuse, d’un poste de contrôle et de suivi physiologique qui servent d’outils de monitoring des animaux tout au long des expérimentations, ponctuelles ou longitudinales. Une salle de salle de chirurgie est mise à la disposition des expérimentateurs, à proximité immédiate des imageurs. Equipée de deux paillasses, disposant de postes d'anesthésie gazeuse, microscopes, etc., elle permet la préparation des modèles animaux ou des journées de formations. Une animalerie conventionnelle (type A1 avec un niveau de confinement L2) permet d'héberger les animaux pendant la durée du protocole d'imagerie. Ces locaux sont agréés par les services vétérinaires pour cinq espèces animales (porcs, lapins, chats, rats, souris). La structure « Bien-Etre Animal » interne au CERMEP accompagne les investigateurs dans leur demande d’autorisation de projet utilisant des animaux à des fins scientifiques (APAFIS – Comité d’éthique). L’essentiel des applications visées aujourd’hui se situe dans le domaine des neurosciences mais la plateforme est ouverte à d’autres thématiques (oncologie, cardiologie, métabolisme, etc.).Les membres d’ANIMAGE accompagnent les équipes de recherche tout au long du protocole de recherche, selon leurs besoins :- définition de la question biologique/physiopathologique/pharmacologique à laquelle pourra répondre l’imagerie,- adéquation de la modalité d’imagerie et du modèle expérimental,- organisation du protocole expérimental,- préparation du modèle animal,- acquisition des images in vivo,- analyse des images et aide à la valorisation scientifique (rapport, article...)

Melanocortin-4 Receptor Mutations and Polymorphisms Do Not Affect Weight Loss after Bariatric Surgery

International audienceBariatric surgery is the most effective long term weight-loss therapy for severe and morbidly obese patients. Melanocortin-4 Receptor (MC4R) mutations, the most frequent known cause of monogenic obesity, affect the regulation of energy homeostasis. The impact of such mutations on weight loss after bariatric surgery is still debated. The objective is to determine the impact of MC4R status on weight loss in obese subjects over one year after bariatric surgery. A total of 648 patients, who were referred to bariatric surgery in a single clinical nutrition department, were genotyped for their MC4R status. The following four groups were categorized: functional MC4R mutations, MC4R single nucleotide polymorphisms (SNPs): Val103Ile (V103L) and Ile251Leu (I251L), MC4R variant rs17782313 (downstream of MC4R) and MC4R SNP A-178C on the promoter. Each patient was matched with two randomly paired controls without mutation. Matching factors were age, sex, baseline weight and type of surgery procedure (Roux-en-Y gastric bypass and adjustable gastric banding). We compared weight loss between cases and controls at 3, 6 and 12 months after surgery. Among 648 patients, we identified 9 carriers of functional MC4R mutations, 10 carriers of MC4R V103L and I251L SNPs, 7 carriers of the rs17792313 variant and 22 carriers of the A-178C SNP. Weight loss at 3, 6 and 12 months did not differ between cases and controls, whatever the MC4R mutations. This is the first case-control study to show that MC4R mutations and polymorphisms do not affect weight loss and body composition over one year after bariatric surgery

Resistance Training and Protein Supplementation Increase Strength After Bariatric Surgery: A Randomized Controlled Trial

International audienceOBJECTIVE: Physical activity and dietary regimens to optimize health outcomes after bariatric surgery are not well known. This study aimed to determine whether resistance training with dietary protein supplementation is effective in maintaining body composition and physical fitness after obesity surgery.METHODS: Seventy-six women with obesity undergoing Roux-en-Y gastric bypass were randomly assigned at the time of surgery to receive either usual care (controls [CON], n = 22), usual care and additional (whey) protein intake (PRO, n = 31), or usual care, additional protein intake, and supervised strength training for 18 weeks (PRO+EX, n = 23). The primary outcome was pre- to 6-month postsurgery change in lean body mass (by dual-energy x-ray absorptiometry). Secondary outcomes included changes in muscle strength (by one-repetition maximum testing).RESULTS: Loss over time in lean body mass did not differ between groups (CON: mean,-8.8 kg; 95% CI: -10.1 to -7.5 kg; PRO: mean, -8.2 kg; 95% CI: -9.3 to -7.1 kg; PRO+EX: mean, -7.7 kg; 95% CI: -9.0 to -6.5 kg; P = 0.899). The increase in relative lower-limb muscle strength was higher in the PRO+EX group (+0.6 [0.3 to 0.8]) versus +0.1 (-0.1 to 0.4) and +0.2 (0.0 to 0.4) kg/kg body mass in CON and PRO groups, respectively (P = 0.021).CONCLUSIONS: Loss in muscle strength observed after bariatric surgery can be overcome by resistance training with additional protein intake

Nutritional and Protein Deficiencies in the Short Term following Both Gastric Bypass and Gastric Banding.

BACKGROUND:The number of morbidly obese patients undergoing bariatric surgery (BS) has increased dramatically in recent years. Therefore, monitoring food intake and its consequences in terms of nutritional status is necessary to prevent nutritional deficiencies. The aim of this study was to analyze the effect of food restriction on nutritional parameters in the short-term (≤3 months) period after BS in morbid obesity. METHOD:In a prospective study, we followed 22 obese women who underwent Roux-en-Y gastric bypass (GBP) or adjustable gastric banding (AGB) at baseline (T0) and 1 (T1) and 3 (T3) months after surgery. We evaluated food intake, nutrient adequacy and serum concentrations of vitamins and minerals known to be at risk for deficiency following BS. RESULTS:Before surgery, we observed suboptimal food intakes, leading to a risk of micronutrient deficiencies. Serum analysis confirmed nutritional deficiencies for iron and thiamine for 27 and 23% of the patients, respectively. The drastic energy and food reduction seen in the short term led to very low probabilities of adequacy for nutrients equivalent across both surgeries. Serum analysis demonstrated a continuous decrease in prealbumin during the follow-up, indicating mild protein depletion in 21 and 57% of GBP patients and 50 and 63% of AGB patients, respectively, at T1 and T3. Regarding vitamins and minerals, systematic supplementation after GBP prevented most nutritional deficiencies. By contrast, AGB patients, for whom there is no systematic supplementation, developed such deficiencies. CONCLUSIONS:Our results suggest that cautious monitoring of protein intake after BS is mandatory. Furthermore, AGB patients might also benefit from systematic multivitamin and mineral supplementation at least in the short term

A Multi-Atlas Based Method for Automated Anatomical Rat Brain MRI Segmentation and Extraction of PET Activity

International audiencePreclinical in vivo imaging requires precise and reproducible delineation of brain structures. Manual segmentation is time consuming and operator dependent. Automated segmentation as usually performed via single atlas registration fails to account for anatomo-physiological variability. We present, evaluate, and make available a multi-atlas approach for automatically segmenting rat brain MRI and extracting PET activies