Bariatric Surgery Improves the Cavernosal Neuronal,Vasorelaxation, and Contraction Mechanisms for Erectile Dysfunction As Result of Amelioration of Glucose Homeostasis in a Diabetic Rat Model

Background

Bariatric surgery is an effective treatment option for both obesity and obesity-related type 2 diabetes mellitus (T2DM). However, little is known regarding the effects of bariatric surgery on erectile dysfunction among patients with T2DM. Therefore, we investigated whether bariatric surgery would lead to structural and biochemical changes in the corpus cavernosum.

Material and Method

Twenty-five male Otsuka Long-Evans Tokushima Fatty rats were assigned to either a control group (sham operation, n = 10) or a bariatric surgery group (gastric bypass surgery, n = 15). Four weeks after the operation, each group of rats was evaluated with an oral glucose tolerance test (OGTT). The penile intracavernous pressure was measured for erectile functional analysis. Histologic evaluation of the tissue was performed with Masson''s trichrome staining. Endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), Rho kinase, and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels in the corpus cavernosum were assayed by using western blot and ELISA.

Results

The mean body weight of the bariatric surgery group was lower than the control group (p = 0.002). The postoperative OGTT result was lower in the bariatric surgery group than in the control group (p = 0.014), and this was lower than the preoperative value (p = 0.037). The intracavernous pressure/mean arterial pressure ratio was higher in the bariatric surgery group compared to the control group (p = 0.021), and a higher cavernosum smooth muscle/collagen ratio was observed in the bariatric surgery group compared to the control group (p = 0.025). Likewise, the expression of eNOS and nNOS was higher in bariatric surgery group than in the control group (p = 0.027 and p = 0.008, respectively). Decreased expression of Rho kinase and levels of 8-OHdG were observed in the bariatric surgery group (p = 0.032).

Conclusion

In this animal model, bariatric surgery appears to ameliorate T2DM-related metabolic dysfunction leading to structural and biochemical changes in the corpus cavernosum, and thus, results in improvement of erectile dysfunction associated with T2DM.     

Transplantation of ATP7B–Transduced Bone Marrow Mesenchymal Stem Cells Decreases Copper Overload in Rats

Background

Recent studies have demonstrated that transplantation of ATP7B-transduced hepatocytes ameliorates disease progression in LEC (Long-Evans Cinnamon) rats, a model of Wilson''s disease (WD). However, the inability of transplanted cells to proliferate in a normal liver hampers long-term treatment. In the current study, we investigated whether transplantation of ATP7B-transduced bone marrow mesenchymal stem cells (BM-MSCs) could decrease copper overload in LEC rats.

Materials and Methods

The livers of LEC rats were preconditioned with radiation (RT) and/or ischemia-reperfusion (IRP) before portal vein infusion of ATP7B-transduced MSCs (MSCs^ATP7B). The volumes of MSCs^ATP7B or saline injected as controls were identical. The expression of ATP7B was analyzed by real-time quantitative polymerase chain reaction (RT-PCR) at 4, 12 and 24 weeks post-transplantation. MSC^ATP7B repopulation, liver copper concentrations, serum ceruloplasmin levels, and alanine transaminase (ALT) and aspartate transaminase (AST) levels were also analyzed at each time-point post-transplantation.

Results

IRP-plus-RT preconditioning was the most effective strategy for enhancing the engraftment and repopulation of transplanted MSCs^ATP7B. This strategy resulted in higher ATP7B expression and serum ceruloplasmin, and lower copper concentration in this doubly preconditioned group compared with the saline control group, the IRP group, and the RT group at all three time-points post-transplantation (p<0.05 for all). Moreover, 24 weeks post-transplantation, the levels of ALT and AST in the IRP group, the RT group, and the IRP-plus-RT group were all significantly decreased compared to those of the saline group (p<0.05 compared with the IRP group and RT group, p<0.01 compared with IRP-plus-RT group); ALT and AST levels were significantly lower in the IRP-plus-RT group compared to either the IRP group or the RT group (p<0.01 and p<0.05. respectively).

Conclusions

These results demonstrate that transplantation of MSCs^ATP7B into IRP-plus-RT preconditioned LEC rats decreased copper overload and was associated with an increase in MSC engraftment and repopulation.     

Diabetes is the main factor accounting for hypomagnesemia in obese subjects

Objective

Type 2 diabetes (T2DM) and obesity are associated with magnesium deficiency. We aimed to determine whether the presence of type 2 diabetes and the degree of metabolic control are related to low serum magnesium levels in obese individuals.

Methods

A) Case-control study: 200 obese subjects [50 with T2DM (cases) and 150 without diabetes (controls)] prospectively recruited. B) Interventional study: the effect of bariatric surgery on serum magnesium levels was examined in a subset of 120 obese subjects (40 with type 2 diabetes and 80 without diabetes).

Results

Type 2 diabetic patients showed lower serum magnesium levels [0.75±0.07 vs. 0.81±0.06 mmol/L; mean difference −0.06 (95% CI −0.09 to −0.04); p<0.001] than non-diabetic patients. Forty-eight percent of diabetic subjects, but only 15% of non-diabetic subjects showed a serum magnesium concentration lower than 0.75 mmol/L. Significant negative correlations between magnesium and fasting plasma glucose, HbA1c, HOMA-IR, and BMI were detected. Multiple linear regression analysis showed that fasting plasma glucose and HbA1c independently predicted serum magnesium. After bariatric surgery serum magnesium increased only in those patients in whom diabetes was resolved, but remain unchanged in those who not, without difference in loss weight between groups. Changes in serum magnesium negatively correlated with changes in fasting plasma glucose and HbA1c. Absolute changes in HbA1c independently predicted magnesium changes in the multiple linear regression analysis.

Conclusions

Our results provide evidence that the presence of diabetes and the degree of metabolic control are essential in accounting for the lower levels of magnesium that exist in obese subjects.     

Micronutrient Levels and Supplement Intake in Pregnancy after Bariatric Surgery: A Prospective Cohort Study

Background

Studies report frequent micronutrient deficiencies after bariatric surgery, but less is known about micronutrient levels of pregnant women after bariatric surgery.

Objective

To prospectively evaluate micronutrient levels and supplement intake in pregnancy following bariatric surgery.

Design

A multicenter prospective cohort study including women with restrictive or malabsorptive types of bariatric surgery. Nutritional deficiencies, together with supplement intake, were screened during pregnancy.

Results

The total population included 18 women in the restrictive and 31 in the malabsorptive group. Most micronutrients were depleted and declined significantly during pregnancy. The proportion of women with low vitamin A and B-1 levels increased to respectively 58 and 17% at delivery (P = 0.005 and 0.002). The proportion of women with vitamin D deficiency decreased from 14% at trimester 1 to 6% at delivery (P = 0.030). Mild anemia was found in respectively 22 and 40% of the women at trimester 1 and delivery. In the first trimester, most women took a multivitamin (57.1%). In the second and third trimester, the majority took additional supplements (69.4 and 73.5%). No associations were found between supplement intake and micronutrient deficiencies.

Conclusion

Pregnant women with bariatric surgery show frequent low micronutrient levels. Supplementation partially normalizes low levels of micronutrients.     

Bariatric Surgery in the United Kingdom: A Cohort Study of Weight Loss and Clinical Outcomes in Routine Clinical Care

Background

Bariatric surgery is becoming a more widespread treatment for obesity. Comprehensive evidence of the long-term effects of contemporary surgery on a broad range of clinical outcomes in large populations treated in routine clinical practice is lacking. The objective of this study was to measure the association between bariatric surgery, weight, body mass index, and obesity-related co-morbidities.

Methods and Findings

This was an observational retrospective cohort study using data from the United Kingdom Clinical Practice Research Datalink. All 3,882 patients registered in the database and with bariatric surgery on or before 31 December 2014 were included and matched by propensity score to 3,882 obese patients without surgery. The main outcome measures were change in weight and body mass index over 4 y; incident diagnoses of type 2 diabetes mellitus (T2DM), hypertension, angina, myocardial infarction (MI), stroke, fractures, obstructive sleep apnoea, and cancer; mortality; and resolution of hypertension and T2DM. Weight measures were available for 3,847 patients between 1 and 4 mo, 2,884 patients between 5 and 12 mo, and 2,258 patients between 13 and 48 mo post-procedure. Bariatric surgery patients exhibited rapid weight loss for the first four postoperative months, at a rate of 4.98 kg/mo (95% CI 4.88–5.08). Slower weight loss was sustained to the end of 4 y. Gastric bypass (6.56 kg/mo) and sleeve gastrectomy (6.29 kg/mo) were associated with greater initial weight reduction than gastric banding (2.77 kg/mo). Protective hazard ratios (HRs) were detected for bariatric surgery for incident T2DM, 0.68 (95% CI 0.55–0.83); hypertension, 0.35 (95% CI 0.27–0.45); angina, 0.59 (95% CI 0.40–0.87);MI, 0.28 (95% CI 0.10–0.74); and obstructive sleep apnoea, 0.55 (95% CI 0.40–0.87). Strong associations were found between bariatric surgery and the resolution of T2DM, with a HR of 9.29 (95% CI 6.84–12.62), and between bariatric surgery and the resolution of hypertension, with a HR of 5.64 (95% CI 2.65–11.99). No association was detected between bariatric surgery and fractures, cancer, or stroke. Effect estimates for mortality found no protective association with bariatric surgery overall, with a HR of 0.97 (95% CI 0.66–1.43). The data used were recorded for the management of patients in primary care and may be subject to inaccuracy, which would tend to lead to underestimates of true relative effect sizes.

Conclusions

Bariatric surgery as delivered in the UK healthcare system is associated with dramatic weight loss, sustained at least 4 y after surgery. This weight loss is accompanied by substantial improvements in pre-existing T2DM and hypertension, as well as a reduced risk of incident T2DM, hypertension, angina, MI, and obstructive sleep apnoea. Widening the availability of bariatric surgery could lead to substantial health benefits for many people who are morbidly obese.     

Association between Duration of Carbon Dioxide Pneumoperitoneum during Laparoscopic Abdominal Surgery and Hepatic Injury: A Meta-Analysis

Background

The aim of this study is to accurately assess whether the duration of intraoperative carbon dioxide pneumoperitoneum (CDP) is associated with the induction of hepatic injury.

Methods

We conducted a systematic review of PubMed, Embase, and Cochrane Library databases (through February 2014) to identify case-match studies that compared high-pressure CDP with low-pressure CDP or varied the duration of CDP in patients who underwent abdominal surgery. The outcome of interest was postoperative liver function (ALT, AST, TB).

Results

Eleven comparative studies involving 2,235 participants were included. Overall, levels of ALT, AST, and TB (on postoperative days 1, 3, and 7) were significantly elevated in the study groups. However, the results of the subanalyses of those who underwent laparoscopic colorectal cancer resection (LCR) versus open colorectal cancer resection (OCR) and those who underwent laparoscopic gastric bypass (LGBP) versus open gastric bypass (OGBP) were inconsistent.

Conclusions

The current evidence suggests that the duration of CDP during laparoscopic abdominal surgery may be associated with hepatic injury. Additional large-scale, randomized, controlled trials are urgently needed to further confirm this.     

Altered Glucose Homeostasis Is Associated with Increased Serum Apelin Levels in Type 2 Diabetes Mellitus

Background

Apelin is an adipokine that plays a role in the regulation of glucose homeostasis and in obesity. The relationship between apelin serum concentration and dysmetabolic conditions such as type 2 diabetes (T2D) is still controversial. Aims of our study are: 1) determine the circulating levels of apelin in a large cohort of Italian subjects with T2D, T1D and in non-diabetic controls; 2) identify putative metabolic determinants of modified apelin concentrations, in order to search possible mechanism of apelin control; 3) investigate changes in apelin levels in response to sharp modifications of glucose/insulin metabolism in T2D obese subjects before and 3 days after bariatric surgery.

Methods

We recruited 369 subjects, 119 with T2D, 113 with T1D and 137 non-diabetic controls. All subjects underwent a complete clinical examination, including anthropometric and laboratory measurements. Serum apelin levels were determined by EIA (immunoenzyme assay).

Results

Patients with T2D had significantly higher serum apelin levels compared to controls (1.23±1.1 ng/mL vs 0.91±0.7 ng/mL, P<0.001) and to T1D subjects (0.73±0.39 ng/mL, P<0.001). Controls and T1D subjects did not differ significantly in apelin levels. Apelin concentrations were directly associated with fasting blood glucose (FBG), body mass index (BMI), basal Disposition Index (DI-0), age, and diagnosis of T2D at bivariate correlation analysis. Multiple regression analysis confirmed that diagnosis of T2D, basal DI-0 and FBG were all determinants of serum apelin levels independently from age and BMI. Bariatric surgery performed in a subgroup of obese diabetic subjects (n = 12) resulted in a significant reduction of apelin concentrations compared to baseline levels (P = 0.01).

Conclusions

Our study demonstrates that T2D, but not T1D, is associated with increased serum apelin levels compared to non-diabetic subjects. This association is dependent on impaired glucose homeostasis, and disappears after bariatric surgery, providing further evidence regarding the relationship between apelin and the regulation of glucose metabolism.     

The association of PNPLA3 variants with liver enzymes in childhood obesity is driven by the interaction with abdominal fat

Background and Aims

A polymorphism in adiponutrin/patatin-like phospholipase-3 gene (PNPLA3), rs738409 C->G, encoding for the I148M variant, is the strongest genetic determinant of liver fat and ALT levels in adulthood and childhood obesity. Aims of this study were i) to analyse in a large group of obese children the role of the interaction of not-genetic factors such as BMI, waist circumference (W/Hr) and insulin resistance (HOMA-IR) in exposing the association between the I148M polymorphism and ALT levels and ii) to stratify the individual risk of these children to have liver injury on the basis of this gene-environment interaction.

Methods

1048 Italian obese children were investigated. Anthropometric, clinical and metabolic data were collected and the PNPLA3 I148M variant genotyped.

Results

Children carrying the 148M allele showed higher ALT and AST levels (p = 0.000006 and p = 0.0002, respectively). Relationships between BMI-SDS, HOMA-IR and W/Hr with ALT were analysed in function of the different PNPLA3 genotypes. Children 148M homozygous showed a stronger correlation between ALT and W/Hr than those carrying the other genotypes (p: 0.0045) and, therefore, 148M homozygotes with high extent of abdominal fat (W/Hr above 0.62) had the highest OR (4.9, 95% C. I. 3.2–7.8, p = 0.00001) to develop pathologic ALT.

Conclusions

We have i) showed for the first time that the magnitude of the association of PNPLA3 with liver enzymes is driven by the size of abdominal fat and ii) stratified the individual risk to develop liver damage on the basis of the interaction between the PNPLA3 genotype and abdominal fat.     

Aldolase predicts subsequent myopathy occurrence in systemic sclerosis

Introduction

Myopathy related to systemic sclerosis (Myo-SSc) is a disabling and unpredictable complication of SSc. We assessed the predictive value of serum aldolase, creatine kinase (CK), alanine transaminase (ALT), aspartate transaminase (AST) and C-reactive protein (CRP) to estimate the risk of developing Myo-SSc.

Methods

We enrolled 137 SSc patients without proximal muscle weakness in a prospective monocentric study to follow them longitudinally over a four-year period. The risk of occurrence of Myo-SSc was ascertained according to the European NeuroMuscular Centre criteria and was analyzed according to levels of plasma aldolase, CK, transaminase enzymes and CRP at inclusion. Performance of each parameter to predict Myo-SSc occurrence was assessed and compared with the others.

Results

The area under the receiver operating characteristic curves (ROC) of plasma aldolase for Myo-SSc occurrence prediction was 0.80 (95% CI: 0.67 to 0.94, P < 0.001), which was higher than that of plasma CK (0.75, P = 0.01), and that of ALT (0.63, P = 0.04). AST and CRP had no predictive value for Myo-SSc occurrence. The best cut-off of aldolase for prediction of Myo-SSc occurrence within three years after inclusion was 9 U/L and higher than the upper normality limit (7 U/L), unlike that of CK and ALT. Myo-SSc occurred more frequently in patients whose plasma aldolase was higher than 9 U/L. Adjusted Hazard Ratio for patients with aldolase > 9 U/L was 10.3 (95% CI: 2.3 to 45.5), P < 0.001.

Conclusions

Increased plasma aldolase level accurately identified SSc patients with high risk to develop subsequent Myo-SSc. This could help initiate appropriate treatment when the disabling muscle damage is still in a reversible stage.     

Acute Post-Bariatric Surgery Increase in Orexin Levels Associates with Preferential Lipid Profile Improvement

Context

Orexin is a recently identified neuropeptide hormone.

Objectives

Acute and long-term post-bariatric changes in Orexin and relationship to post-operative metabolic outcomes.

Design and Participants

Men and women undergoing biliopancreatic diversion with duodenal switch bariatric surgery (n = 76, BMI≥35 kg/m²) were evaluated for body composition and plasma parameters at baseline, acutely (1 and 5 days) and long-term (6 and 12 months) post-surgery.

Setting

University Hospital Centre, Canada.

Interventions and Main Outcome Measures

Groups were subdivided based on acute (average 1 and 5 day) changes in Orexin prior to weight loss: (i)>10% Orexin decrease (n = 33, Orexin_DEC) and (ii)>10% Orexin increase (n = 20, Orexin_INC), to evaluate impact on long-term changes.

Results

Both groups had comparable preoperative Orexin levels, BMI, age, sex distribution, diabetes and lipid lowering medication, plasma glucose and lipid parameters except for apolipoproteinB (p<0.007). Orexin increase was rapid and maintained throughout one year, while Orexin_DEC subjects remained significantly lower throughout. Over 12 months, changes in BMI, fat mass, and %fat mass were comparable. Fasting glucose and insulin increased immediately 1-day post-operatively, decreasing rapidly (5-day) and declining thereafter with the Orexin_INC group remaining lower than the Orexin_DEC group throughout (p = 0.001). Similarly, plasma cholesterol, triglyceride, LDL-C and HDL-C decreased at 1-day, increased slightly (5-day), except HDL-C, then decreased over 1 year, with greater decreases in Orexin_INC group relative to Orexin_DEC group.

Conclusion

Rapid postoperative increases in plasma Orexin are associated with better improvement of glucose and lipid profiles following bariatric surgery.     

Liver enzymes: interaction analysis of smoking with alcohol consumption or BMI, comparing AST and ALT to γ-GT

Background

A detrimental interaction between smoking and alcohol consumption with respect serum γ-glutamyltransferase (γ-GT) has recently been described. The underlying mechanisms remain unknown. The present work aimed to provide further insights by examining similar interactions pertaining to aspartate and alanine transaminase (AST, ALT), routine liver markers less prone to enzyme induction.

Methodology/Principal Findings

The present cross-sectional analysis was based on records from routine occupational health examinations of 15,281 male employees predominantly of the construction industry, conducted from 1986 to 1992 in Southern Germany. Associations of smoking intensity with log-transformed activities of γ-GT, AST, and ALT were examined in regression models adjusted for potential confounders and including an interaction of smoking with alcohol consumption or body mass index (BMI). Statistically significant interactions of smoking were observed with both alcohol consumption (AST and ALT, each with P<0.0001) and BMI (AST only, P<0.0001). The interactions all were in the same directions as for γ-GT, i.e. synergistic with alcohol and opposite with BMI.

Conclusion

The patterns of interaction between smoking and alcohol consumption or BMI with respect to AST and ALT resembled those observed for γ-GT. This renders enzyme induction a less probable mechanism for these associations, whereas it might implicate exacerbated hepatocellular vulnerability and injury.     

De novo lipogenesis in adipose tissue is associated with course of morbid obesity after bariatric surgery

Objective

De novo lipogenesis is involved in fatty acid biosynthesis and could be involved in the regulation of the triglyceride storage capacity of adipose tissue. However, the association between lipogenic and lipolytic genes and the evolution of morbidly obese subjects after bariatric surgery remains unknown. In this prospective study we analyze the association between the improvement in the morbidly obese patients as a result of bariatric surgery and the basal expression of lipogenic and lipolytic genes.

Methods

We study 23 non diabetic morbidly obese patients who were studied before and 7 months after bariatric surgery. Also, we analyze the relative basal mRNA expression levels of lipogenic and lipolytic genes in epiploic visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (SAT).

Results

When the basal acetyl-CoA carboxylase 1 (ACC1), acetyl-CoA synthetase 2 (ACSS2) and ATP citrate lyase (ACL) expression in SAT was below percentile-50, there was a greater decrease in weight (P = 0.006, P = 0.034, P = 0.026), body mass index (P = 0.008, P = 0.033, P = 0.034) and hip circumference (P = 0.033, P = 0.021, P = 0.083) after bariatric surgery. In VAT, when the basal ACSS2 expression was below percentile-50, there was a greater decrease in hip circumference (P = 0.006). After adjusting for confounding variables in logistic regression models, only the morbidly obese patients with SAT or VAT ACSS2 expression≥P50 before bariatric surgery had a lower percentage hip circumference loss (P = 0.039; VAT: P = 0.033).

Conclusions

A lower basal ACSS2, ACC1 and ACL expression, genes involved in de novo lipogenesis, is associated with a better evolution of anthropometric variables after bariatric surgery. Thus, the previous state of the pathways involved in fatty acid metabolism may have repercussions on the improvement of these patients.     

Surgically Induced Interpregnancy Weight Loss and Prevalence of Overweight and Obesity in Offspring

Introduction

According to the fetal overnutrition hypothesis, obesity in pregnancy predisposes the offspring to obesity. Previous studies have suggested that after biliopancreatic surgery for obesity, the offspring is less likely to be obese. This study aims to further compare the BMI development of children born before and after maternal surgical weight loss.

Method

Women with at least one child born before and one child born after bariatric surgery were identified by record-linkage. Information about maternal BMI was extracted from medical records, as was information about the children''s BMI from birth to 10 years of age. We retrieved BMI data at four years of age for 340 children, born to 223 women (164 children born before surgery (BS), 176 children born after surgery (AS)). We evaluated prevalence of overweight/obesity and mean BMI in children born BS and AS at the ages of four, six and ten using GEE regression models. For 71 families, where we had complete data on mother and both children, we used a fixed-effects regression model to explore the association between differences in maternal BMI in w10 of the pre- and post-operative pregnancies with siblings'' BMI differences at age four.

Results

In no age group did we see a significantly reduced prevalence of overweight/obesity AS. For 10-year-old girls, the AS group had significantly higher rates of obesity. There was no association between differences in maternal BMI in early pregnancy and differences in siblings'' BMI at four years of age (β = −0.01, CI 95% = −0.11; 0.09).

Conclusions

We have been unable to demonstrate any effect of bariatric surgery on weight development in offspring. It seems unlikely that restrictive bariatric surgery conveys a protective effect in offspring with regards to obesity.     

Plasma NOV/CCN3 Levels Are Closely Associated with Obesity in Patients with Metabolic Disorders

Objective

Evidence points to a founder of the multifunctional CCN family, NOV/CCN3, as a circulating molecule involved in cardiac development, vascular homeostasis and inflammation. No data are available on the relationship between plasma NOV/CCN3 levels and cardiovascular risk factors in humans. This study investigated the possible relationship between plasma NOV levels and cardiovascular risk factors in humans.

Methods

NOV levels were measured in the plasma from 594 adults with a hyperlipidemia history and/or with lipid-lowering therapy and/or a body mass index (BMI) >30 kg/m². Correlations were measured between NOV plasma levels and various parameters, including BMI, fat mass, and plasma triglycerides, cholesterol, glucose, and C-reactive protein. NOV expression was also evaluated in adipose tissue from obese patients and rodents and in primary cultures of adipocytes and macrophages.

Results

After full multivariate adjustment, we detected a strong positive correlation between plasma NOV and BMI (r = 0.36 p<0.0001) and fat mass (r = 0.33 p<0.0005). According to quintiles, this relationship appeared to be linear. NOV levels were also positively correlated with C-reactive protein but not with total cholesterol, LDL-C or blood glucose. In patients with drastic weight loss induced by Roux-en-Y bariatric surgery, circulating NOV levels decreased by 28% (p<0.02) and 48% (p<0.0001) after 3 and 6 months, respectively, following surgery. In adipose tissue from obese patients, and in human primary cultures NOV protein was detected in adipocytes and macrophages. In mice fed a high fat diet NOV plasma levels and its expression in adipose tissue were also significantly increased compared to controls fed a standard diet.

Conclusion

Our results strongly suggest that in obese humans and mice plasma NOV levels positively correlated with NOV expression in adipose tissue, and support a possible contribution of NOV to obesity-related inflammation.     

Novel Algorithm for Non-Invasive Assessment of Fibrosis in NAFLD

Introduction

Various conditions of liver disease and the downsides of liver biopsy call for a non-invasive option to assess liver fibrosis. A non-invasive score would be especially useful to identify patients with slow advancing fibrotic processes, as in Non-Alcoholic Fatty Liver Disease (NAFLD), which should undergo histological examination for fibrosis.

Patients/Methods

Classic liver serum parameters, hyaluronic acid (HA) and cell death markers of 126 patients undergoing bariatric surgery for morbid obesity were analyzed by machine learning techniques (logistic regression, k-nearest neighbors, linear support vector machines, rule-based systems, decision trees and random forest (RF)). Specificity, sensitivity and accuracy of the evaluated datasets to predict fibrosis were assessed.

Results

None of the single parameters (ALT, AST, M30, M60, HA) did differ significantly between patients with a fibrosis score 1 or 2. However, combining these parameters using RFs reached 79% accuracy in fibrosis prediction with a sensitivity of more than 60% and specificity of 77%. Moreover, RFs identified the cell death markers M30 and M65 as more important for the decision than the classic liver parameters.

Conclusion

On the basis of serum parameters the generation of a fibrosis scoring system seems feasible, even when only marginally fibrotic tissue is available. Prospective evaluation of novel markers, i.e. cell death parameters, should be performed to identify an optimal set of fibrosis predictors.     

Effect of dental status on changes in mastication in patients with obesity following bariatric surgery

Background

Patients scheduled for bariatric surgery (BS) are encouraged to chew slowly in order to optimise the digestion process. The influence of dental status on patients'' ability to comply with advice on chewing behaviour is poorly documented. This study aims to compare modifications of chewing function before and after BS in three groups of obese patients differing in dental status.

Method and Findings

A cohort of 46 obese women provided three groups: FD group: fully dentate (7–10 functional dental units [FU]); PD group: partially dentate (4–6 FU) without partial dentures; DW group: partial and complete denture wearers. Chewing time (CT), number of chewing cycles (CC), and chewing frequency (CF) were measured before and after surgery during mastication of standardised samples of raw carrot, peanuts, banana, apple and jelly. The median particle-size distribution (D50) of the pre-swallowed bolus was also evaluated for peanut and carrot. Before surgery, the PD and DW groups exhibited greater mean CCs and CTs than the FD group (SNK p<0.05) and produced a bolus with higher granulometry (SNK, p<0.05) than the FD group. After surgery, CT and CC increased for all groups and for all foods, but not statistically significant for jelly. The resulting changes in bolus granulometry observed depended on both food and dental status. The granulometry of carrot bolus remained as fine or as coarse in FD and DW groups respectively as it was before surgery while it was significantly decreased in the PD group (Student''s test, p<0.001).

Conclusions

After bariatric surgery, all the obese patients, regardless of dental status modified their chewing kinematics. The effects of this chewing behaviour on bolus granulometry depended on dental status and type of food. Further studies are needed to understand better the impact of dental status on feeding behaviour and nutrition in patients with obesity.     

Peptide YY regulates bone remodeling in mice: a link between gut and skeletal biology

Background & Aims

Gastrointestinal peptides are increasingly being linked to processes controlling the maintenance of bone mass. Peptide YY (PYY), a gut-derived satiety peptide of the neuropeptide Y family, is upregulated in some states that also display low bone mass. Importantly, PYY has high affinity for Y-receptors, particularly Y1R and Y2R, which are known to regulate bone mass. Anorexic conditions and bariatric surgery for obesity influence circulating levels of PYY and have a negative impact on bone mass, but the precise mechanism behind this is unclear. We thus examined whether alterations in PYY expression affect bone mass.

Methods

Bone microstructure and cellular activity were analyzed in germline PYY knockout and conditional adult-onset PYY over-expressing mice at lumbar and femoral sites using histomorphometry and micro-computed tomography.

Results

PYY displayed a negative relationship with osteoblast activity. Male and female PYY knockout mice showed enhanced osteoblast activity, with greater cancellous bone mass. Conversely, PYY over-expression lowered osteoblast activity in vivo, via a direct Y1 receptor mediated mechanism involving MAPK stimulation evident in vitro. In contrast to PYY knockout mice, PYY over expression also altered bone resorption, as indicated by greater osteoclast surface, despite the lack of Y-receptor expression in osteoclastic cells. While evident in both sexes, cellular changes were generally more pronounced in females.

Conclusions

These data demonstrate that the gut peptide PYY is critical for the control of bone remodeling. This regulatory axis from the intestine to bone has the potential to contribute to the marked bone loss observed in situations of extreme weight loss and higher circulating PYY levels, such as anorexia and bariatric obesity surgery, and may be important in the maintenance of bone mass in the general population.     

Does the Method of Weight Loss Effect Long-Term Changes in Weight,Body Composition or Chronic Disease Risk Factors in Overweight or Obese Adults? A Systematic Review

Background

Differences in biological changes from weight loss by energy restriction and/or exercise may be associated with differences in long-term weight loss/regain.

Objective

To assess the effect of weight loss method on long-term changes in weight, body composition and chronic disease risk factors.

Data Sources

PubMed and Embase were searched (January 1990-October 2013) for studies with data on the effect of energy restriction, exercise (aerobic and resistance) on long-term weight loss. Twenty articles were included in this review.

Study Eligibility Criteria

Primary source, peer reviewed randomized trials published in English with an active weight loss period of >6 months, or active weight loss with a follow-up period of any duration, conducted in overweight or obese adults were included.

Study Appraisal and Synthesis Methods

Considerable heterogeneity across trials existed for important study parameters, therefore a meta-analysis was considered inappropriate. Results were synthesized and grouped by comparisons (e.g. diet vs. aerobic exercise, diet vs. diet + aerobic exercise etc.) and study design (long-term or weight loss/follow-up).

Results

Forty percent of trials reported significantly greater long-term weight loss with diet compared with aerobic exercise, while results for differences in weight regain were inconclusive. Diet+aerobic exercise resulted in significantly greater weight loss than diet alone in 50% of trials. However, weight regain (∼55% of loss) was similar in diet and diet+aerobic exercise groups. Fat-free mass tended to be preserved when interventions included exercise.