Polyphenol Supplementation Did Not Affect Insulin Sensitivity and Fat Deposition During One-Month Overfeeding in Randomized Placebo-Controlled Trials in Men and in Women.

Two randomized placebo-controlled double-blind paralleled trials (42 men in Lyon, 19 women in Lausanne) were designed to test 2 g/day of a grape polyphenol extract during 31 days of high calorie-high fructose overfeeding. Hyperinsulinemic-euglycemic clamps and test meals with [1,1,1-13C3]-triolein were performed before and at the end of the intervention. Changes in body composition were assessed by dual-energy X-ray absorptiometry (DEXA). Fat volumes of the abdominal region and liver fat content were determined in men only, using 3D-magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) at 3T. Adipocyte's size was measured in subcutaneous fat biopsies. Bodyweight and fat mass increased during overfeeding, in men and in women. While whole body insulin sensitivity did not change, homeostasis model assessment of insulin resistance (HOMA-IR) and the hepatic insulin resistance index (HIR) increased during overfeeding. Liver fat increased in men. However, grape polyphenol supplementation did not modify the metabolic and anthropometric parameters or counteract the changes during overfeeding, neither in men nor in women. Polyphenol intake was associated with a reduction in adipocyte size in women femoral fat. Grape polyphenol supplementation did not counteract the moderated metabolic alterations induced by one month of high calorie-high fructose overfeeding in men and women. The clinical trials are registered under the numbers NCT02145780 and NCT02225457 at ClinicalTrials.gov and available at https://clinicaltrials.gov/ct2/show/NCT02145780 and https://clinicaltrials.gov/ct2/show/NCT02225457.

GnRH neurons recruit astrocytes in infancy to facilitate network integration and sexual maturation.

Neurons that produce gonadotropin-releasing hormone (GnRH), which control fertility, complete their nose-to-brain migration by birth. However, their function depends on integration within a complex neuroglial network during postnatal development. Here, we show that rodent GnRH neurons use a prostaglandin D2 receptor DP1 signaling mechanism during infancy to recruit newborn astrocytes that 'escort' them into adulthood, and that the impairment of postnatal hypothalamic gliogenesis markedly alters sexual maturation by preventing this recruitment, a process mimicked by the endocrine disruptor bisphenol A. Inhibition of DP1 signaling in the infantile preoptic region, where GnRH cell bodies reside, disrupts the correct wiring and firing of GnRH neurons, alters minipuberty or the first activation of the hypothalamic-pituitary-gonadal axis during infancy, and delays the timely acquisition of reproductive capacity. These findings uncover a previously unknown neuron-to-neural-progenitor communication pathway and demonstrate that postnatal astrogenesis is a basic component of a complex set of mechanisms used by the neuroendocrine brain to control sexual maturation.

Identification of Milk and Cheese Intake Biomarkers in Healthy Adults Reveals High Interindividual Variability of Lewis System-Related Oligosaccharides.

BACKGROUND: The use of biomarkers of food intake (BFIs) in blood and urine has shown great promise for assessing dietary intake and complementing traditional dietary assessment tools whose use is prone to misreporting. OBJECTIVE: Untargeted LC-MS metabolomics was applied to identify candidate BFIs for assessing the intake of milk and cheese and to explore the metabolic response to the ingestion of these foods. METHODS: A randomized controlled crossover study was conducted in healthy adults [5 women, 6 men; age: 23.6 ± 5.0 y; BMI (kg/m2): 22.1 ± 1.7].  After a single isocaloric intake of milk (600 mL), cheese (100 g), or soy-based drink (600 mL), serum and urine samples were collected postprandially up to 6 h and after fasting after 24 h. Untargeted metabolomics was conducted using LC-MS. Discriminant metabolites were selected in serum by multivariate statistical analysis, and their mass distribution and postprandial kinetics were compared. RESULTS: Serum metabolites discriminant for cheese intake had a significantly lower mass distribution than metabolites characterizing milk intake (P = 4.1 × 10-4). Candidate BFIs for milk or cheese included saccharides, a hydroxy acid, amino acids, amino acid derivatives, and dipeptides. Two serum oligosaccharides, blood group H disaccharide (BGH) and Lewis A trisaccharide (LeA), specifically reflected milk intake but with high interindividual variability. The 2 oligosaccharides showed related but opposing trends: subjects showing an increase in either oligosaccharide did not show any increase in the other oligosaccharide. This result was confirmed in urine. CONCLUSIONS: New candidate BFIs for milk or cheese could be identified in healthy adults, most of which were related to protein metabolism. The increase in serum of LeA and BGH after cow-milk intake in adults calls for further investigations considering the beneficial health effects on newborns of such oligosaccharides in maternal milk. The trial is registered at clinicaltrials.gov as NCT02705560.

[Bariatric surgery†: sleeve versus gastric bypass, how to make the decision†?] / Chirurgie bariatrique†: sleeve gastrectomy ou bypass gastrique, comment choisir†?

Considering the growing epidemic of obesity worldwide, bariatric surgery is considered the most effective measure for significant weight loss and coping with comorbidities associated with obesity once it is established. Indications for bariatric surgery in Switzerland are clearly defined, but the type of intervention is often debated. As the gastric band gradually disappears, the number of sleeve gastrectomy (SG) is constantly increasing and has surpassed the traditional gastric bypass worldwide, because of the theoretically safer profile of this intervention. The purpose of this article is to summarize the most common types of bariatric surgery, their advantages and disadvantages, and their indication according to the patient's profile.

Face à l'épidémie croissante d'obésité dans le monde, la chirurgie bariatrique est considérée comme la mesure la plus efficace pour une perte de poids significative et pour faire face aux comorbidités liées à l'obésité une fois que celle-ci est installée. Les indications à une chirurgie bariatrique en Suisse sont clairement définies mais le type d'intervention reste souvent matière à débat. Alors que l'anneau gastrique disparaît peu à peu, le nombre de sleeve gastrectomy (SG) est en constante augmentation et a surpassé celui du traditionnel bypass gastrique dans le monde, en raison du profil théoriquement plus sûr de cette intervention. L'objectif de cet article a pour but de résumer les différents types de chirurgie bariatrique les plus répandus, leurs avantages et leurs inconvénients, ainsi que leur indication selon le profil du patient.

[Can surgery treat type 2 diabetes ? Yes, according to international companies]. / La chirurgie peut-elle traiter le diabète de type 2 ? Oui, selon les sociétés internationales.

Type 2 diabetes (DM2) and obesity are chronic diseases that often coexist with considerable morbidity and mortality. Approximately 85 % of all DM2 patients have a body mass index (BMI) ranking them as overweight (BMI 25­29,9 kg/m2) or obese (BMI > 30 kg/m2). Metabolic surgery is the only treatment for diabetes that results in long-term remission in 23 to 60 % of patients in the office depending on the preoperative duration of diabetes and the severity of the disease. This review presents evidence for the use of metabolic surgery (CM) as a primary treatment for DM2, potential mechanisms of its effects, and recommendations for its use in expanded patient populations.

Le diabète de type 2 (D2) et l'obésité sont des maladies chroniques qui coexistent souvent avec une morbidité et une mortalité considérables. Environ 85 % de tous les patients atteints de D2 ont un indice de masse corporelle (IMC) les classant en surpoids (IMC 25­29,9 kg/m2) ou obèses (IMC > 30 kg/m2). La chirurgie métabolique est le seul traitement du diabète qui entraîne une rémission à long terme chez 23 à 60 % des patients en fonction de la durée préopératoire du diabète et de la gravité de la maladie. Cette revue présente des évidences en faveur de l'utilisation de la chirurgie métabolique (CM) comme traitement principal du D2, des mécanismes potentiels de ses effets, et des recommandations pour son utilisation dans des populations de patients élargies.

[Centers for bariatric medicine : why and how ?] / Centres de médecine bariatrique : pourquoi, comment ?

Obesity is a chronic, complex and relapsing disease. Because of this complexity, work up and follow up of affected patients implicate different specialists, working in synergy to diagnose and treat obesity and its complications. This follow up is specialized, and should be available in integrated centers of bariatric medicine offering all modalities of treatments with proven efficacy, whether medical, surgical or psychotherapeutical.

L'obésité est une maladie chronique, complexe et récidivante. Du fait de cette complexité, la prise en charge clinique des patients affectés doit impliquer différents spécialistes, travaillant en synergie pour diagnostiquer et traiter les différentes facettes de l'obésité et de ses complications. L'organisation de cette prise en charge spécialisée devrait s'articuler autour de centres intégrés de médecine bariatrique offrant tous les traitements reconnus efficaces, qu'ils soient médicaux, chirurgicaux ou psychothérapeutiques.

[Towards bariatric surgery : taking your time preserves you from loosing your time]. / Préparation à la chirurgie bariatrique : lorsque prendre du temps n'est pas en perdre.

Obesity has become a worldwide public health concern. Bariatric surgery is nowadays the most effective treatment to lose weight and control somatic comorbidities of this disease. However, a careful preparation of the patients undergoing bariatric surgery seems mandatory, despite the existence of a feeling of emergency that is often shared by the therapeutic team, and thus difficult to handle. In this context, the importance to address psychological issues such as patients' representation of their body while they will be confronted to a major physical transformation cannot be over-emphasized. Taking time is crucial to create a therapeutic context that raises the patients' awareness of their underlying psychological functioning.

Le traitement de l'obésité est devenu une problématique de santé publique mondiale. La chirurgie bariatrique est actuellement le moyen le plus efficace pour perdre du poids et contrôler les comorbidités somatiques de cette maladie. Toutefois, une préparation approfondie des patients semble incontournable malgré une impulsion d'urgence souvent partagée par les soignants qui peinent à refréner cette dynamique. L'importance d'anticiper le vécu psychique du patient, face à un corps qui va rapidement se trouver confronté à une modification de son schéma et de son image corporels, nous semble indispensable. Prendre du temps est essentiel afin d'aménager un espace permettant au patient de conscientiser les changements à venir et de pouvoir les affronter sereinement pour le reste de sa vie.

[Multidisciplinary management of dumping syndromes after bariatric surgery]. / Prise en charge pluridisciplinaire des syndromes de dumping après chirurgie bariatrique.

Dumping syndromes are a frequent complication of gastric or bariatric surgery and include early and late dumping. Early dumping is a consequence of rapid delivery of hyperosmolar nutrients into the bowel. Late dumping is the result of a reactive hypoglycemia induced by a hyperinsulinemic response. These syndromes are becoming increasingly prevalent with the rising incidence of bariatric surgery. Effective management of these complications requires multidisciplinary collaboration. First line management of early and late dumping syndrome involves specific dietary and behavioral modifications which generally improve the quality of life of patients.

Les syndromes de dumping sont une complication fréquente de la chirurgie gastrique ou bariatrique. Le dumping précoce est la conséquence d'un passage rapide d'aliments peu digérés à haut pouvoir osmotique dans l'intestin grêle. Le dumping tardif est causé par une hypoglycémie réactive à une réponse insulinique excessive. La prévalence de ces syndromes augmente en raison du nombre croissant de chirurgies bariatriques. Leur prise en charge requiert une collaboration multidisciplinaire. Le traitement de ces dumpings consiste en première ligne en des modifications diététiques et comportementales, propres à chaque type de dumping, qui permettent généralement d'améliorer significativement la qualité de vie des patients.

Treatment challenges in type 1 diabetes after roux-en-Y gastric bypass.

Bariatric surgery is an effective treatment of type 2 diabetes in obese patients. The obesity epidemic does not spare patients with type 1 diabetes mellitus (T1DM), but there is no consensus regarding the role of surgery in the management of obese T1DM patients. Published data consistently report significant weight loss after surgery in obese T1DM patients, but long-term glycaemic control remains difficult to achieve. Here we present our experience with a challenging patient and a review of the literature. Our patient successfully underwent a roux-en-Y gastric bypass (RYGB) when she was 28 years old. Five years after surgery, she was diagnosed with latent autoimmune diabetes of adults and insulin therapy was initiated. Insulin therapy proved very difficult to adjust, with frequent episodes of postprandial hyperglycaemia. These difficulties could only be overcome by the initiation of a subcutaneous insulin infusion using a sensor-augmented insulin pump with automated suspension. This change allowed better glycaemic control. Despite considerable weight loss with a concomitant decrease in insulin requirement, glycaemic control remained difficult after surgery. Due to their different impacts on glucose kinetics, the type of surgical operation should be part of the assessment. These patients might benefit from sensor-augmented insulin pump therapy with automated insulin suspension after bariatric surgery. The decision for surgical intervention in these patients should be carefully weighed against the difficulties in achieving adequate glycaemic control.

A vital region for human glycoprotein hormone trafficking revealed by an LHB mutation.

Glycoprotein hormones are complex hormonally active macromolecules. Luteinizing hormone (LH) is essential for the postnatal development and maturation of the male gonad. Inactivating Luteinizing hormone beta (LHB) gene mutations are exceptionally rare and lead to hypogonadism that is particularly severe in males. We describe a family with selective LH deficiency and hypogonadism in two brothers. DNA sequencing of LHB was performed and the effects of genetic variants on hormone function and secretion were characterized by mutagenesis studies, confocal microscopy and functional assays. A 20-year-old male from a consanguineous family had pubertal delay, hypogonadism and undetectable LH. A homozygous c.118_120del (p.Lys40del) mutation was identified in the patient and his brother, who subsequently had the same phenotype. Treatment with hCG led to pubertal development, increased circulating testosterone and spermatogenesis. Experiments in HeLa cells revealed that the mutant LH is retained intracellularly and showed diffuse cytoplasmic distribution. The mutated LHB heterodimerizes with the common alpha-subunit and can activate its receptor. Deletion of flanking glutamic acid residues at positions 39 and 41 impair LH to a similar extent as deletion of Lys40. This region is functionally important across all heterodimeric glycoprotein hormones, because deletion of the corresponding residues in hCG, follicle-stimulating hormone and thyroid-stimulating hormone beta-subunits also led to intracellular hormone retention. This novel LHB mutation results in hypogonadism due to intracellular sequestration of the hormone and reveals a discrete region in the protein that is crucial for normal secretion of all human glycoprotein hormones.

[The Lausanne Obesity Cohort: why and how?]. / La Cohorte obésité de Lausanne (COOL): pourquoi, comment?

Bariatric surgery has become the treatment of choice for severe obesity. The significant weight loss induced by these procedures is accompanied by spectacular improvements in the metabolic comorbidities that participate in morbidity and mortality of obesity. However, several questions remain open regarding the identification of patients that will benefit the most from the intervention or the long-term outcomes in terms of weight and co-morbidities. The Cohort obesity of Lausanne was initiated in order to try and answer some of these questions, and more specifically to identify predictive factors of long-term response to gastric by-pass.

[Increased risk of alcohol use disorders after bariatric surgery]. / Chirurgie bariatrique et risque accru de dépendance à l'alcool.

After bariatric surgery the risk of alcohol use disorders is increased. This risk is greater after Roux-en-Y gastric bypass than after sleeve gastrectomy or gastric banding. These differences can be explained by modification in alcohol metabolism after gastric bypass, which increases peak alcohol levels. Other mechanisms that might be responsible for increased alcohol use disorders after bariatric surgery are neuro-biological contributors and addiction transfer from binge eating to alcohol consumption. Collaboration with a team specialized in alcoholism treatment is needed for the management of such patients.

[Pregnancy after bariatric surgery]. / Grossesse après chirurgie bariatrique.

Bariatric surgery interventions are rapidly growing and most are performed on female patients. Thus, pregnancies after bariatric surgery are increasingly common. Awareness of the consequences and risks of bariatric surgery on subsequent pregnancies is important. Literature data report a reduction of the usual pregnancy risks of pregnancies in obese patients, but also an increased risk of small-for-gestational-age infants, possibly related to nutritional deficiencies. A careful screening for micronutrient deficiencies is therefore already advised before conception. Nutritional follow-up and serious evaluation of any abdominal complaints are recommended as well during pregnancy.

Postoperative Albumin Drop Is a Marker for Surgical Stress and a Predictor for Clinical Outcome: A Pilot Study.

Background. Surgical stress during major surgery may be related to adverse clinical outcomes and early quantification of stress response would be useful to allow prompt interventions. The aim of this study was to evaluate the acute phase protein albumin in the context of the postoperative stress response. Methods. This prospective pilot study included 70 patients undergoing frequent abdominal procedures of different magnitude. Albumin (Alb) and C-reactive protein (CRP) levels were measured once daily starting the day before surgery until postoperative day (POD) 5. Maximal Alb decrease (Alb Δ min) was correlated with clinical parameters of surgical stress, postoperative complications, and length of stay. Results. Albumin values dropped immediately after surgery by about 10 g/L (42.2 ± 4.5 g/L preoperatively versus 33.8 ± 5.3 g/L at day 1, P < 0.001). Alb Δ min was correlated with operation length (Pearson ρ = 0.470, P < 0.001), estimated blood loss (ρ = 0.605, P < 0.001), and maximal CRP values (ρ = 0.391, P = 0.002). Alb Δ min levels were significantly higher in patients having complications (10.0 ± 5.4 versus 6.1 ± 5.2, P = 0.005) and a longer hospital stay (ρ = 0.285, P < 0.020). Conclusion. Early postoperative albumin drop appeared to reflect the magnitude of surgical trauma and was correlated with adverse clinical outcomes. Its promising role as early marker for stress response deserves further prospective evaluation.

A Novel Approach to Major Surgery: Tracking Its Pathophysiologic Footprints.

BACKGROUND: To study the 'metabolic profile' of different surgical procedures and correlate it with pertinent surgical details and postoperative complications. METHODS: We conducted a prospective pilot study of 70 patients, ten for each of the seven following groups: (1) laparoscopic cholecystectomy, (2) incisional hernia repair, (3) laparoscopic and (4) open colon surgery, (5) upper gastrointestinal, (6) hepatic, and (7) pancreatic resections. Biochemical assessment included white blood cell count (WBC), C-reactive protein (CRP), glucose, triglycerides (TG), albumin (Alb), and pre-albumin (Pre-Alb), from the day before surgery until 5 days thereafter. Biological markers were compared for major versus minor surgery groups, which were defined on a clinical basis. Univariable analysis was used to identify risk factors for postoperative complications and p < 0.05 was the significance threshold. RESULTS: Common findings in all surgery groups were the acute inflammatory response (↑: WBC, CRP, ↓: TG, Alb, pre-Alb). Using cut-off values of 240 min operative (OR) time and 300 ml estimated blood loss (EBL), laparoscopic cholecystectomy, incisional hernia repair, and laparoscopic colectomy could be distinguished from open colectomy, upper gastrointestinal, liver, and pancreas resections. In a biochemical level, increased CRP and reduced postoperative Alb levels were highly discriminative of all types of 'major surgery.' Significant risk factors for postoperative complications were age, male gender, malignancy, longer OR time, higher blood loss, high CRP, and low Alb levels. CONCLUSIONS: Biochemically, CRP and Alb levels can help quantify the magnitude of the surgical trauma, which is correlated with adverse outcomes.

Inflammatory and metabolic responses to high-fat meals with and without dairy products in men.

Postprandial inflammation is an important factor for human health since chronic low-grade inflammation is associated with chronic diseases. Dairy products have a weak but significant anti-inflammatory effect on postprandial inflammation. The objective of the present study was to compare the effect of a high-fat dairy meal (HFD meal), a high-fat non-dairy meal supplemented with milk (HFM meal) and a high-fat non-dairy control meal (HFC meal) on postprandial inflammatory and metabolic responses in healthy men. A cross-over study was conducted in nineteen male subjects. Blood samples were collected before and 1, 2, 4 and 6 h after consumption of the test meals. Plasma concentrations of insulin, glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, TAG and C-reactive protein (CRP) were measured at each time point. IL-6, TNF-α and endotoxin concentrations were assessed at baseline and endpoint (6 h). Time-dependent curves of these metabolic parameters were plotted, and the net incremental AUC were found to be significantly higher for TAG and lower for CRP after consumption of the HFM meal compared with the HFD meal; however, the HFM and HFD meals were not different from the HFC meal. Alterations in IL-6, TNF-α and endotoxin concentrations were not significantly different between the test meals. The results suggest that full-fat milk and dairy products (cheese and butter) have no significant impact on the inflammatory response to a high-fat meal.

Semaphorin7A regulates neuroglial plasticity in the adult hypothalamic median eminence.

Reproductive competence in mammals depends on the projection of gonadotropin-releasing hormone (GnRH) neurons to the hypothalamic median eminence (ME) and the timely release of GnRH into the hypothalamic-pituitary-gonadal axis. In adult rodents, GnRH neurons and the specialized glial cells named tanycytes periodically undergo cytoskeletal plasticity. However, the mechanisms that regulate this plasticity are still largely unknown. We demonstrate that Semaphorin7A, expressed by tanycytes, plays a dual role, inducing the retraction of GnRH terminals and promoting their ensheathment by tanycytic end feet via the receptors PlexinC1 and Itgb1, respectively. Moreover, Semaphorin7A expression is regulated during the oestrous cycle by the fluctuating levels of gonadal steroids. Genetic invalidation of Semaphorin7A receptors in mice induces neuronal and glial rearrangements in the ME and abolishes normal oestrous cyclicity and fertility. These results show a role for Semaphorin7A signalling in mediating periodic neuroglial remodelling in the adult ME during the ovarian cycle.

Leptin and smoking cessation: secondary analyses of a randomized controlled trial assessing physical activity as an aid for smoking cessation.

BACKGROUND: Smokers have a lower body weight compared to non-smokers. Smoking cessation is associated with weight gain in most cases. A hormonal mechanism of action might be implicated in weight variations related to smoking, and leptin might be implicated. We made secondary analyses of an RCT, with a hypothesis-free exploratory approach to study the dynamic of leptin following smoking cessation. METHODS: We measured serum leptin levels among 271 sedentary smokers willing to quit who participated in a randomized controlled trial assessing a 9-week moderate-intensity physical activity intervention as an aid for smoking cessation. We adjusted leptin for body fat levels. We performed linear regressions to test for an association between leptin levels and the study group over time. RESULTS: One year after smoking cessation, the mean serum leptin change was +3.23 mg/l (SD 4.89) in the control group and +1.25 mg/l (SD 4.86) in the intervention group (p of the difference < 0.05). When adjusted for body fat levels, leptin was higher in the control group than in the intervention group (p of the difference < 0.01). The mean weight gain was +2.91 (SD 6.66) Kg in the intervention and +3.33 (SD 4.47) Kg in the control groups, respectively (p not significant). CONCLUSIONS: Serum leptin levels significantly increased after smoking cessation, in spite of substantial weight gain. The leptin dynamic might be different in chronic tobacco users who quit smoking, and physical activity might impact the dynamic of leptin in such a situation. Clinical trial registration number: NCT00521391.

A dose-response strategy reveals differences between normal-weight and obese men in their metabolic and inflammatory responses to a high-fat meal.

A dose-response strategy may not only allow investigation of the impact of foods and nutrients on human health but may also reveal differences in the response of individuals to food ingestion based on their metabolic health status. In a randomized crossover study, we challenged 19 normal-weight (BMI: 20-25 kg/m(2)) and 18 obese (BMI: >30 kg/m(2)) men with 500, 1000, and 1500 kcal of a high-fat (HF) meal (60.5% energy from fat). Blood was taken at baseline and up to 6 h postprandially and analyzed for a range of metabolic, inflammatory, and hormonal variables, including plasma glucose, lipids, and C-reactive protein and serum insulin, glucagon-like peptide-1, interleukin-6 (IL-6), and endotoxin. Insulin was the only variable that could differentiate the postprandial response of normal-weight and obese participants at each of the 3 caloric doses. A significant response of the inflammatory marker IL-6 was only observed in the obese group after ingestion of the HF meal containing 1500 kcal [net incremental AUC (iAUC) = 22.9 ± 6.8 pg/mL × 6 h, P = 0.002]. Furthermore, the net iAUC for triglycerides significantly increased from the 1000 to the 1500 kcal meal in the obese group (5.0 ± 0.5 mmol/L × 6 h vs. 6.0 ± 0.5 mmol/L × 6 h; P = 0.015) but not in the normal-weight group (4.3 ± 0.5 mmol/L × 6 h vs. 4.8 ± 0.5 mmol/L × 6 h; P = 0.31). We propose that caloric dose-response studies may contribute to a better understanding of the metabolic impact of food on the human organism. This study was registered at clinicaltrials.gov as NCT01446068.