Sustainable and Green Corrosion Inhibition of Mild Steel: Insights from Electrochemical and Computational Approaches.

Natural and fragrant compounds, essential oils (EOs) extracted from plants through hydrodistillation, are gaining popularity as eco-friendly and sustainable agents to protect metals and alloys from corrosion in acidic environments. This research focused on extracting and characterizing an EO obtained from the Cuminum cyminum (CC) plant native to India. The study aimed to evaluate the inhibitory properties of this EO on mild steel in a 0.5 M HCl solution at different concentrations. Various analytical techniques, including potentiodynamic polarization curves, electrochemical impedance spectroscopy, optical microscopy, infrared spectroscopy, and proton magnetic resonance, were employed to assess the effectiveness of this EO extract. Our findings indicate that the Cuminum cyminum L (CCL) extract effectively reduces the corrosion of mild steel in hydrochloric acid with an inhibition efficiency ranging from 79.69 to 98.76%. The optimal inhibition concentration was 2 g/L of EO, and surface analysis confirmed the formation of a protective layer. Furthermore, our results suggest that the inhibitor binds to the metal surface through a charge-transfer process, creating a protective film. Finally, we utilized theoretical calculations and molecular dynamics simulations to elucidate the inhibition mechanism on both a global and local scale.

Quince seed mucilage/ß-cyclodextrin/Mmt-Na+-co-poly (methacrylate) based pH-sensitive polymeric carriers for controlled delivery of Capecitabine.

In current work, quince seed mucilage and ß-Cyclodextrin based pH regulated hydrogels were developed using aqueous free radical polymerization to sustain Capecitabine release patterns and to overcome its drawbacks, such as high dose frequency, short half-life, and low bioavailability. Developed networks were subjected to thermal analysis, Fourier transforms infrared spectroscopy, powder x-ray diffraction, elemental analysis, scanning electron microscopy, equilibrium swelling, and in-vitro release investigations to assess the network system's stability, complexation, morphology, and pH responsiveness. Thermally stable pH-responsive cross-linked networks were formed. Nanocomposite hydrogels were prepared by incorporating Capecitabine-containing clay into the swollen hydrogels. All the formulations exhibited equilibrium swelling ranging from 67.98 % to 92.98 % at pH 7.4. Optimum Capecitabine loading (88.17 %) was noted in the case of hydrogels, while it was 74.27 % in nanocomposite hydrogels. Excellent gel content (65.88 %-93.56 %) was noticed among developed formulations. Elemental analysis ensured the successful incorporation of Capecitabine. Nanocomposite hydrogels released 80.02 % longer than hydrogels after 30 h. NC hydrogels had higher t1/2 (10.57 h), AUC (121.52 µg.h/ml), and MRT (18.95 h) than hydrogels in oral pharmacokinetics. These findings imply that the pH-responsive carrier system may improve Capecitabine efficacy and reduce dosing frequency in cancer therapy. Toxicity profiling proved the system's safety, non-toxicity, and biocompatibility.

The 'Behavioral Balance Model': A new perspective on the aetiology and therapy of obesity.

Obesity is a debilitating disease of global proportions that necessitates refined, concept-driven therapeutic approaches. Policy makers, the public and even health care professionals, but also individuals with obesity harbour many misconceptions regarding this disease, which leads to prejudice, negative attitudes, stigmatization, discrimination, self-blame, and failure to provide and finance adequate medical care. Decades of intensive, successful scientific research on obesity have only had a very limited effect on this predicament. We propose a science-based, easy-to-understand conceptual model that synthesizes the complex pathogenesis of obesity including biological, psychological, social, economic and environmental aspects with the aim to explain and communicate better the nature of obesity and currently available therapeutic modalities. According to our integrative 'Behavioral Balance Model', 'top-down cognitive control' strategies are implemented (often with limited success) to counterbalance the increased 'bottom-up drive' to gain weight, which is triggered by biological, psycho-social and environmental mechanisms in people with obesity. Besides offering a deeper understanding of obesity, the model also highlights why there is a strong need for multimodal therapeutic approaches that may not only increase top-down control but also reduce a pathologically increased bottom-up drive.

Long-term outcomes after gastric bypass surgery in patients with craniopharyngioma-related hypothalamic obesity-Three cases with 7, 8, and 14 years follow-up.

INTRODUCTION: Craniopharyngioma is a brain tumor, resection which often results in hypothalamic damage leading to severe obesity. While small case series and case-control studies have shown the benefits of bariatric surgery in patients with craniopharyngioma-related hypothalamic obesity, long-term results (>5 years) have not been reported so far. METHODS: We analyzed data from 3 cases with craniopharyngioma-related hypothalamic obesity who had undergone (one proximal, two very long limb distal) Roux-en Y gastric bypass (RYGB) surgery 7, 8, and 14 years before their latest follow-up visit. RESULTS: Percentage of total weight loss varied across the 3 patients (11%, 26%, 32%). Preexisting type 2 diabetes markedly improved in 2 patients with one showing a temporary and one a persisting remission. At RYGB surgery one patient was diagnosed to have liver cirrhosis (intraoperative biopsy), but liver function remained stable or even improved during a 7-year follow-up period. One patient required proximalisation of lower anastomosis (distal RYGB) because of severe hypoproteinemia and diarrhea which resolved after revision. Another patient temporarily developed alcohol abuse that led to weight regain, but his weight decreased when alcohol consumption became under control. Importantly, all three patients stated in a standardized questionnaire that they have benefited and that they would recommend RYGB surgery to another person. CONCLUSION: Despite showing an unsatisfying weight loss result in one patient and distinct complications in the other two patients, all patients clearly showed long-term persisting benefits. Moreover, self-reported outcomes confirm that it was the right decision to recommend RYGB to our patients displaying craniopharyngioma-related hypothalamic obesity.

Biohydrogen production in a continuous liquid/gas hollow fiber membrane bioreactor: Efficient retention of hydrogen producing bacteria via granule and biofilm formation.

The aim of this work was to develop a continuous liquid/gas membrane bioreactor (L/G MBR), i.e. a fermenting module including hollow fibers membrane for L/G separation, for biohydrogen production by dark fermentation. Originally seeded with sludge from a wastewater treatment plant, the L/G MBR underwent a complete stop for eight months. It was then operated without further reseeding. In the present experiment, performed 551 days after the last reseeding, average hydrogen yield of 1.1 ± 0.2 mol per mol glucose added and hydrogen productivity of 135 ± 22 mL/L/h were reached, with acetate and butyrate as the main metabolite products. DNA sequence analysis revealed that Clostridium beijerinckii, Clostridium pasteurianum and Enterobacter sp. were dominant in liquid outlet, in a biofilm on the surface of the hollow fibers and in microbial granules. The L/G MBR has potential for the concentration and the long-term maintenance of an active hydrogen-producing bacterial community without need for reseeding.

Cardiorespiratory Fitness is Associated with Glycated Hemoglobin and Triglyceride Levels in Severely Obese Men: A Retrospective Clinical Data Analysis.

BACKGROUND: Even subjects with severe obesity show a wide range of metabolic health states, with some showing marked alterations in glucose and lipid metabolism whereas others do not. In severely obese women, we could recently show that the degree of cardiorespiratory fitness is, independently of body mass and age, associated with several markers of glucose and lipid metabolism. AIMS: In our retrospective study on a clinical data set, we questioned whether such an association also exists in severely obese men. METHODS: Cardiorespiratory fitness, i. e. workload (Wpeak) and oxygen uptake (V̇O2,peak) at peak exercise, was assessed by a bicycle spiroergometry in 133 severely obese men (all BMI>35 kg m-2). The following metabolic blood markers were also measured: Fasting serum glucose, insulin, triglycerides (TG), total, low-, high-density cholesterol (Chol, LDL, HDL), uric acid, and whole blood glycated hemoglobin (HbA1c). The Chol/HDL ratio and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) were also calculated. RESULTS: Multiple stepwise linear regression models including age, body mass, and smoking status as independent variables revealed that Wpeak and V̇O2,peak, explained 4.5 to 10.7% of variance in HbA1c and TG (all beta<- 0.22; all p<0.02). Including fat free mass instead of body mass in respective models revealed that both Wpeak and V̇O2,peak were predictors of HbA1c and TG (all beta<- 0.265; all p<0.013), respectively, while Wpeak also accounted for variance in glucose and Chol (both beta<- 0.259; both p<0.023). CONCLUSIONS: Similar to previous observations in women, our data indicate that cardiorespiratory fitness assessed by bicycle ergospirometry test is associated with glucose and lipid metabolism in severely obese men. The strength of the found associations suggest a mild to moderate influence of cardiorespiratory fitness on metabolic health in severe obesity.

Resting energy expenditure after Roux-en Y gastric bypass surgery.

BACKGROUND: The mechanisms by which Roux-en Y gastric bypass surgery (RYGB) provokes weight loss are incompletely understood. Enhanced energy expenditure may be one contributing mechanism. Previous results on changes in resting energy expenditure (REE) after RYGB are inconsistent. OBJECTIVES: The aim of the present study was to assess changes in REE after RYGB and whether REE predicts weight loss (percentage weight loss). SETTING: Obesity Clinic. METHODS: REE was measured by indirect calorimetry (mREE) before and 1 year after RYGB in 233 patients with severe obesity (175 women; all body mass index ≥35.0 kg·m-2) and mREE was compared with predicted REE (pREE) and expressed as percentage of pREE (%pREE). For calculation of pREE, 2 new equations were developed from an independent reference group of overweight and obese patients (852 patients; body mass index range: 27.4-73.0 kg·m-2) that were examined in exactly the same setting as the bariatric patients that were followed-up after RYGB. The new equations were based on either anthropometric (pREE-BM, %pREE-BM) or body composition (pREE-BC; %pREE-BC) parameters. RESULTS: After RYGB, absolute mREE was reduced by 20.4 ± 11.0% (-458 ± 277 kcal·d-1; P<.001). Compared with pREE-BM (post-%REE-BM) and pREE-BC (post-%REE-BC), mREE was 2.3 ± 9.4% and 1.6 ± 9.5%, respectively, higher (both P ≤ .03). Post-%pREE-BM and post- %pREE-BC after RYGB were positively correlated with percentage weight loss (r = .206 and r = .231; both P ≤ .003). CONCLUSIONS: Data indicate a slightly higher mREE than pREE after RYGB. Although the underlying mechanisms of this observation remain to be elucidated our finding may play a role for weight loss outcomes after the surgery.

QT Interval Shortening After Bariatric Surgery Depends on the Applied Heart Rate Correction Equation.

BACKGROUND: A shortening of electrocardiographic QT interval has been observed in obese subjects after weight loss, but previous results may have been biased by inappropriate heart rate (HR) correction. METHODS: Electrocardiography (ECG) recordings of 49 (35 females) severely obese patients before and 12 months after Roux-en-Y gastric bypass (RYGB) surgery were analysed. QT interval (QTc) was calculated by using four different equations, i.e. Bazett, Fridericia, Framingham and Hodges. RESULTS: Irrespectively of the used correction formula, QTc interval length was reduced after the surgery (QTcBazett -31 ± 18 ms; QTcFridericia -12 ± 15 ms; QTcFramingham -14 ± 15 ms; QTcHodges -9 ± 15 ms; all Ps < 0.001), but QTcBazett reduction was significantly greater than the reduction in QTc calculated upon the other three equations (all Ps < 0.001). Moreover, changes in QTcBazett (P < 0.001) but not in QTcFridericia, QTcFramingham and QTcHodges (all Ps > 0.05) were significantly correlated with concurrent changes in HR. Multivariate regression analyses revealed a significant independent association of serum insulin levels with QTcFridericia, QTcFramingham and QTcHodges values (all Ps < 0.05) preoperatively, whilst changes in QTc interval length after the surgery were not consistently associated to concurrent changes in metabolic traits. CONCLUSIONS: Our data show that the extent of weight loss-associated QTc interval shortening largely depends on the applied HR correction equation and appears to be overestimated when the most popular Bazett's equation is used.

A genetic variant in proximity to the gene LYPLAL1 is associated with lower hunger feelings and increased weight loss following Roux-en-Y gastric bypass surgery.

OBJECTIVE: Bariatric surgery is the most efficient treatment of severe obesity. We investigated to what extent BMI- or waist-hip ratio (WHR)-related genetic variants are associated with excess BMI loss (EBMIL) two years after Roux-en-Y gastric bypass (RYGB) surgery, and elucidated the affected biological pathways. METHODS: Two-hundred fifty-one obese patients (age: 43 ± 10.7, preoperative BMI: 45.1 ± 6.1 kg/m(2), 186 women) underwent RYGB surgery and were followed up after two years with regard to BMI. Patients were genotyped for 32 single-nucleotide polymorphisms (SNPs) that were investigated with regard to their impact on response to RYGB and preoperatively measured Three Factor Eating Questionnaire (TFEQ) scores. RESULTS: Homozygous T carriers of the SNP rs4846567 in proximity to the Lysophospholipase-like 1 (LYPLAL1) gene showed a 7% higher EBMIL compared to wild-type and heterozygous carriers (p = 0.031). TT-allele carriers showed furthermore lower scores for Hunger (74%, p < 0.001), lower Disinhibition (53%, p < 0.001), and higher Cognitive restraint (21%, p = 0.017) than GG/GT carriers in the TFEQ. Patients within the lowest quartile of Hunger scores had a 32% greater EBMIL compared to patients in the highest quartile (p < 0.001). CONCLUSION: The LYPLAL1 genotype is associated with differences in eating behavior and loss of extensive body weight following RYGB surgery. Genotyping and the use of eating behavior-related questionnaires may help to estimate the RYGB-associated therapy success.

A Genetic Risk Score Is Associated with Weight Loss Following Roux-en Y Gastric Bypass Surgery.

BACKGROUND: Currently, Roux-en Y gastric bypass (RYGB) is the most efficient therapy for severe obesity. Weight loss after surgery is, however, highly variable and genetically influenced. Genome-wide association studies have identified several single nucleotide polymorphisms (SNP) associated with body mass index (BMI) and waist-hip ratio (WHR). We aimed to identify two genetic risk scores (GRS) composed of weighted BMI and WHR-associated SNPs to estimate their impact on excess BMI loss (EBMIL) after RYGB surgery. METHODS: Two hundred and thirty-eight obese patients (BMI 45.1 ± 6.2 kg/m(2), 74 % women), who underwent RYGB, were genotyped for 35 BMI and WHR-associated SNPs and were followed up after 2 years. SNPs with high impact on post-surgical weight loss were filtered out using a random forest model. The filtered SNPs were combined into a GRS and analyzed in a linear regression model. RESULTS: An up to 11 % lower EBMIL with higher risk score was estimated for two GRS models (P = 0.026 resp. P = 0.021) composed of seven BMI-associated SNPs (closest genes: MC4R, TMEM160, PTBP2, NUDT3, TFAP2B, ZNF608, MAP2K5, GNPDA2, and MTCH2) and of three WHR-associated SNPs (closest genes: HOXC13, LYPLAL1, and DNM3-PIGC). Patients within the lowest GRS quartile had higher EBMIL compared to patients within the other three quartiles in both models. CONCLUSIONS: We identified two GRSs composed of BMI and WHR-associated SNPs with significant impact on weight loss after RYGB surgery using random forest analysis as a SNP selection tool. The GRS may be useful to pre-surgically evaluate the risks for patients undergoing RYGB surgery.

Comprehensive assessment of physical functioning in bariatric surgery candidates compared with subjects without obesity.

BACKGROUND: Obesity appears to be associated with reduced physical performance, but comprehensive assessments of physical functioning are lacking in subjects with severe obesity, in particular in comparison with subjects without obesity. This precludes an objective assessment of the degree of impairment. OBJECTIVE: To compare motor skills and cardiopulmonary fitness between subjects with severe obesity (OB) (i.e., candidates for bariatric surgery) and control subjects without obesity (non-OB). SETTING: Cantonal Hospital, Switzerland. METHODS: Flexibility, movement speed, balance, maximal isometric strength, and cardiopulmonary fitness were tested in 45 OB (body mass index: 42.6±.9 kg/m(2); age: 35±1.7 years; 33 women) and 32 non-OB (body mass index: 23±.4 kg/m(2); age: 38.5±2.1 years; 25 women) subjects. RESULTS: In comparison with the non-OB group, the OB group showed reduced shoulder flexibility (P<.001) but comparable hamstrings flexibility (P = .3). Speed-related tasks (i.e., timed up-and-go test and timed lying-to-standing test) indicated that the OB group was slower than the non-OB group (all P<.007). Strength-related tasks indicated a greater absolute back muscle and knee-extensor strength (all P<.002) in the OB group with no difference in knee-flexor strength (both P>.8). However, when related to weight, the OB group showed reduced maximal strength (all P<.002). Bicycle spiroergometry indicated that absolute oxygen consumption at peak exercise and at the anaerobic threshold did not differ between groups (both P>.06). Related to weight, however, values were lower in the OB than in the non-OB group (both P< .001). CONCLUSION: Data indicate a differential pattern of functional impairment in bariatric surgery candidates compared with subjects without obesity. These findings might help to establish tailored intervention protocols to improve physical performance in such subjects.

Subjective and objective physical activity patterns after Roux-en Y gastric bypass surgery compared with non-operated obese and non-obese control women.

INTRODUCTION: Previous studies on physical activity after bariatric surgery provided inconsistent results. The aim of our study was to comprehensively assess physical activity by subjective (questionnaires) and objective (accelerometry) measures in women who had undergone Roux-en Y gastric bypass (RYGB) surgery and to compare results with those of women displaying grade II or higher obesity and of non-obese control women. METHODS: Our cross-sectional case-control study included 12 women in each group (RYGB, obese, non-obese). Wrist accelerometry was performed over 5 days. Two questionnaires were used to assess women's self-reported leisure- and work-time and sport-related physical activity. RESULTS: Accelerometry indicated a lower physical activity in RYGB women than in non-obese women in particular during the weekend (p=0.010), while there was no difference between RYGB and obese women (p=0.57). Questionnaires revealed that RYGB women self-report a greater leisure- and work-time physical activity than obese women and also greater work-related physical activity than non-obese women (all p≤0.032). In contrast, sport-related activities were reduced in RYGB as compared with non-obese women (p=0.011), while there was no difference between RYGB and obese women (p=0.51). Comparison of the obese and non-obese group revealed less leisure-time and sport-related activities in the obese women (both p≤0.002). DISCUSSION: Despite the preliminary character of our rather small study, data suggest a differential physical activity pattern in women who have previously undergone RYGB surgery that is characterized by rare sport activities, an increased subjective work-related physical activity and objectively reduced physical activity during the weekend as compared with non-obese control women.

Metabolomic fingerprint of severe obesity is dynamically affected by bariatric surgery in a procedure-dependent manner.

BACKGROUND: Obesity is associated with multiple diseases. Bariatric surgery is the most effective therapy for severe obesity that can reduce body weight and obesity-associated morbidity. The metabolic alterations associated with obesity and respective changes after bariatric surgery are incompletely understood. OBJECTIVE: We comprehensively assessed metabolic alterations associated with severe obesity and distinct bariatric procedures. DESIGN: In our longitudinal observational study, we applied a (1)H-nuclear magnetic resonance-based global, untargeted metabolomics strategy on human serum samples that were collected before and repeatedly ≤1 y after distinct bariatric procedures [i.e., a sleeve gastrectomy, proximal Roux-en Y gastric bypass (RYGB), and distal RYGB]. For comparison, we also analyzed serum samples from normal-weight and less-obese subjects who were matched for 1-y postoperative body mass index (BMI) values of the surgical groups. RESULTS: We identified a metabolomic fingerprint in obese subjects that was clearly discriminated from that of normal-weight subjects. Furthermore, we showed that bariatric surgery (sleeve gastrectomy and proximal and distal RYGB) dynamically affected this fingerprint in a procedure-dependent manner, thereby establishing new fingerprints that could be discriminated from those of BMI-matched and normal-weight control subjects. Metabolites that largely contributed to the metabolomic fingerprints of severe obesity were aromatic and branched-chain amino acids (elevated), metabolites related to energy metabolism (pyruvate and citrate; elevated), and metabolites suggested to be derived from gut microbiota (formate, methanol, and isopropanol; all elevated). CONCLUSION: Our data indicate that bariatric surgery, irrespective of the specific kind of procedure used, reverses most of the metabolic alterations associated with obesity and suggest profound changes in gut microbiome-host interactions after the surgery. This trial was registered at clinicaltrials.gov as NCT02480322.

Altered intestinal neuroendocrine gene expression in humans with obesity.

OBJECTIVE: Gastrointestinal hormones are critically involved in the regulation of food intake and body weight. Previous studies support an interplay between gastrointestinal hormones and the serotonergic system. This study explored intestinal neuroendocrine expression patterns in humans with obesity versus nonobese humans. METHODS: Jejunum samples were collected from 164 humans with obesity (120 women; BMI (mean ± SD): 43.5 ± 6.6 kg/m(2) ) while they underwent Roux-en-Y gastric bypass surgery and from 18 nonobese humans (7 women; BMI: 23.5 ± 3.0 kg/m(2) ) undergoing distinct intestinal surgeries. mRNA expression of cholecystokinin (CCK), peptide YY3-36 (PYY), nesfatin1, ghrelin, ghrelin O-acyltransferase (GOAT), leptin, leptin receptor (leptinR), glucagon-like-peptide 1 receptor (GLP1R), serotonin transporter (SERT), tryptophan hydroxylase 1 (TPH1), and serotonin receptor 3A (5HT3A R) was determined with qRT-PCR. Ghrelin and GOAT protein expression was quantified using immunohistological stainings. Statistical analyses were performed with SPSS. RESULTS: Jejunum samples from humans with obesity showed a higher expression of GOAT (mRNA and protein), TPH1, and SERT mRNA compared with the nonobese humans (all P < 0.05). Positive correlations were observed between TPH1, CCK, PYY, and nesfatin1 in nonobese and GOAT, ghrelin, TPH1, SERT, CCK, and PYY in humans with obesity (all P < 0.01). CONCLUSIONS: Our top-down approach substantiates the dysregulation of jejunal neuroendocrine hormones in obesity.

The Role of FTO and Vitamin D for the Weight Loss Effect of Roux-en-Y Gastric Bypass Surgery in Obese Patients.

BACKGROUND: A recent study in children demonstrated that the rs9939609 single-nucleotide polymorphism in the fat mass and obesity (FTO) gene influences prospective weight gain, however, only in those who were vitamin D-deficient. If this might also be the case for Roux-en-Y gastric bypass (RYGB), surgery-induced weight loss is however unknown. The objective of this study is to examine if the magnitude of RYGB surgery-induced weight loss after 2 years depends on patients' FTO rs9939609 genotype (i.e., TT, AT, and AA) and presurgery vitamin D status (<50 nmol/L equals deficiency). METHODS: Before and at 24 months after RYGB surgery, BMI was measured in 210 obese patients (mean BMI 45 kg/m(2), 72 % females). Serum 25-hydroxyvitamin D3 levels were also repeatedly measured. Following surgery, vitamin D was supplemented. Possible weight loss differences between genotypes were tested with multiple linear regressions. RESULTS: The per-allele effect of each FTO A-allele on excessive BMI loss (EBMIL) was 3 % (P = 0.02). When split by baseline status, the EBMIL of vitamin D-deficient patients carrying AA exceeded that of vitamin D-deficient patients carrying TT by ~14 % (P = 0.03). No such genotypic differences were found in patients without presurgery vitamin D deficiency. Post-surgery serum levels of vitamin D did not differ between groups. CONCLUSIONS: Our data suggest that presurgery vitamin D levels influence the size of genotype effects of FTO rs9939609 on RYGB surgery-induced weight loss in obese patients.

Roux-en Y gastric bypass surgery induces genome-wide promoter-specific changes in DNA methylation in whole blood of obese patients.

CONTEXT: DNA methylation has been proposed to play a critical role in many cellular and biological processes. OBJECTIVE: To examine the influence of Roux-en-Y gastric bypass (RYGB) surgery on genome-wide promoter-specific DNA methylation in obese patients. Promoters are involved in the initiation and regulation of gene transcription. METHODS: Promoter-specific DNA methylation in whole blood was measured in 11 obese patients (presurgery BMI >35 kg/m(2), 4 females), both before and 6 months after RYGB surgery, as well as once only in a control group of 16 normal-weight men. In addition, body weight and fasting plasma glucose were measured after an overnight fast. RESULTS: The mean genome-wide distance between promoter-specific DNA methylation of obese patients at six months after RYGB surgery and controls was shorter, as compared to that at baseline (p<0.001). Moreover, postsurgically, the DNA methylation of 51 promoters was significantly different from corresponding values that had been measured at baseline (28 upregulated and 23 downregulated, P<0.05 for all promoters, Bonferroni corrected). Among these promoters, an enrichment for genes involved in metabolic processes was found (n = 36, P<0.05). In addition, the mean DNA methylation of these 51 promoters was more similar after surgery to that of controls, than it had been at baseline (P<0.0001). When controlling for the RYGB surgery-induced drop in weight (-24% of respective baseline value) and fasting plasma glucose concentration (-16% of respective baseline value), the DNA methylation of only one out of 51 promoters (~2%) remained significantly different between the pre-and postsurgery time points. CONCLUSIONS: Epigenetic modifications are proposed to play an important role in the development of and predisposition to metabolic diseases, including type II diabetes and obesity. Thus, our findings may form the basis for further investigations to unravel the molecular effects of gastric bypass surgery. CLINICAL TRIAL: ClinicalTrials.gov NCT01730742.

Effect of high sugar intake on glucose transporter and weight regulating hormones in mice and humans.

OBJECTIVE: Sugar consumption has increased dramatically over the last decades in Western societies. Especially the intake of sugar-sweetened beverages seems to be a major risk for the development of obesity. Thus, we compared liquid versus solid high-sugar diets with regard to dietary intake, intestinal uptake and metabolic parameters in mice and partly in humans. METHODS: Five iso-caloric diets, enriched with liquid (in water 30% vol/vol) or solid (in diet 65% g/g) fructose or sucrose or a control diet were fed for eight weeks to C57bl/6 mice. Sugar, liquid and caloric intake, small intestinal sugar transporters (GLUT2/5) and weight regulating hormone mRNA expression, as well as hepatic fat accumulation were measured. In obese versus lean humans that underwent either bariatric surgery or small bowel resection, we analyzed small intestinal GLUT2, GLUT5, and cholecystokinin expression. RESULTS: In mice, the liquid high-sucrose diet caused an enhancement of total caloric intake compared to the solid high-sucrose diet and the control diet. In addition, the liquid high-sucrose diet increased expression of GLUT2, GLUT5, and cholecystokinin expression in the ileum (P<0.001). Enhanced liver triglyceride accumulation was observed in mice being fed the liquid high-sucrose or -fructose, and the solid high-sucrose diet compared to controls. In obese, GLUT2 and GLUT5 mRNA expression was enhanced in comparison to lean individuals. CONCLUSIONS: We show that the form of sugar intake (liquid versus solid) is presumably more important than the type of sugar, with regard to feeding behavior, intestinal sugar uptake and liver fat accumulation in mice. Interestingly, in obese individuals, an intestinal sugar transporter modulation also occurred when compared to lean individuals.

Waist circumference and related anthropometric indices are associated with metabolic traits in severely obese subjects.

Increased waist circumference (WC) and related anthropometric indices have been shown to be, independently of body weight and body mass index (BMI), associated with adverse metabolic traits in many populations. It is unknown, however, whether WC also predicts adverse metabolic traits in severely obese subjects displaying a BMI greater than 35 kg/m2. To address this question, we analyzed a dataset including 838 severely obese patients (597 women, BMI 44.6 ± 6.2 kg/m2; 241 men, BMI 44.3 ± 5.7 kg/m2). Body weight, height, WC, hip circumference, and blood pressure were measured in all subjects along with the following metabolic blood markers: fasting glucose, insulin, glycolized hemoglobin levels, triglycerides, total cholesterol, low- and high-density cholesterol, and uric acid. Multivariate regression analyses indicated that WC as well as related anthropometric indices, in particular those accounting for subjects' height, were associated with many metabolic variables independently of body weight and BMI. In general, height-adjusted WC indices were more closely associated with metabolic traits in women than in men. Collectively, our findings suggest that body fat distribution also plays an important role in determining metabolic traits in severely obese subjects and that WC represents a valuable marker of abdominal/visceral obesity in this population.