Impact of maternal cardiometabolic status after bariatric surgery on the association between telomere length and adiposity in offspring.

The impact of bariatric surgery on metabolic and inflammatory status are reflected in the epigenetic profile and telomere length mediated by the changes in the metabolic status of the patients. This study compared the telomere length of children born before versus after maternal bariatric surgery as a surrogate to test the influence of the mother's metabolic status on children's telomere length. DNA methylation telomere length (DNAmTL) was estimated from Methylation-EPIC BeadChip array data from a total of 24 children born before and after maternal bariatric surgery in the greater Quebec City area. DNAmTL was inversely associated with chronological age in children (r = - 0.80, p < 0.001) and significant differences were observed on age-adjusted DNAmTL between children born before versus after the maternal bariatric surgery. The associations found between body mass index and body fat percentage with DNAmTL in children born after the surgery were influenced by maternal triglycerides, TG/HDL-C ratio and TyG index. This study reports the impact of maternal bariatric surgery on offspring telomere length. The influence of maternal metabolic status on the association between telomere length and markers of adiposity in children suggests a putative modulating effect of bariatric surgery on the cardiometabolic risk in offspring.

Determinants of Cardiorespiratory Fitness After Bariatric Surgery: Insights From a Randomised Controlled Trial of a Supervised Training Program.

BACKGROUND: Severely obese patients have decreased cardiorespiratory fitness (CRF) and poor functional capacity. Bariatric surgery-induced weight loss improves CRF, but the determinants of this improvement are not well known. We aimed to assess the determinants of CRF before and after bariatric surgery and the impact of an exercise training program on CRF after bariatric surgery. METHODS: Fifty-eight severely obese patients (46.1 ± 6.1 kg/m2, 78% women) were randomly assigned to either an exercise group (n = 39) or usual care (n = 19). Exercise training was conducted from the 3rd to the 6th months after surgery. Anthropometric measurements, abdominal and mid-thigh computed tomographic scans, resting echocardiography, and maximal cardiopulmonary exercise testing was performed before bariatric surgery and 3 and 6 months after surgery. RESULTS: Weight, fat mass, and fat-free mass were reduced significantly at 3 and 6 months, without any additive impact of exercise training in the exercise group. From 3 to 6 months, peak aerobic power (V̇O2peak) increased significantly (P < 0.0001) in both groups but more importantly in the exercise group (exercise group: from 18.6 ± 4.2 to 23.2 ± 5.7 mL/kg/min; control group: from 17.4 ± 2.3 to 19.7 ± 2.4 mL/kg/min; P value, group × time = 0.01). In the exercise group, determinants of absolute V̇O2peak (L/min) were peak exercise ventilation, oxygen pulse, and heart rate reserve (r2 = 0.92; P < 0.0001), whereas determinants of V̇O2peak indexed to body mass (mL/kg/min) were peak exercise ventilation and early-to-late filling velocity ratio (r2 = 0.70; P < 0.0001). CONCLUSIONS: A 12-week supervised training program has an additive benefit on cardiorespiratory fitness for patients who undergo bariatric surgery.

Ten-year remission rates in insulin-treated type 2 diabetes after biliopancreatic diversion with duodenal switch.

BACKGROUND: Biliopancreatic diversion with duodenal switch (BPD-DS) confers the highest rate of type 2 diabetes (T2D) remission compared with other bariatric procedures. Previous studies suggest that type of antidiabetic therapy used before surgery and duration of disease influence postsurgical glycemic outcomes. Short-term, progressive improvement in insulin sensitivity and beta-cell function after metabolic surgery in patients with noninsulin-treated T2D has been demonstrated. Whether patients with more advanced disease can achieve sustained remission remains unclear. OBJECTIVE: The aim of this study was to assess long-term glycemic outcomes in insulin-treated patients with T2D after BPD-DS and identify predictors of sustained diabetes remission or relapse. SETTING: University-affiliated tertiary care center. METHODS: Data from 141 patients with insulin-treated T2D who underwent BPD-DS between 1994 and 2006 with 10 years of follow-up data were collected from a prospective electronic database. RESULTS: Follow-up was available in 132 patients (91%). At 10 years after metabolic surgery, 90 patients (68.1%) had a complete remission of diabetes, 3 (2.3%) had a partial remission, 21 (15.9%) had an improvement, and 3 (2.3%) were unchanged in their diabetes status. Fourteen patients died during the 10-year follow-up period. Relapse after an initial period of remission occurred in 15 (11.4%) patients. Insulin discontinuation was achieved in 97%. Duration of diabetes was an independent predictor of nonremission at 10 years. CONCLUSIONS: The BPD-DS maintains remission at 10 years postoperatively in patients with more advanced diabetes. Long-term benefits of the BPD-DS on weight loss and glycemic control should be considered when offering metabolic surgery to patients with insulin-treated T2D.

Acute and Chronic Impact of Biliopancreatic Diversion with Duodenal Switch Surgery on Plasma Lipoprotein(a) Levels in Patients with Severe Obesity.

BACKGROUND: Elevated lipoprotein(a) (Lp(a)) level is an independent risk factor for cardiovascular diseases. Lifestyle intervention studies targeting weight loss revealed little to no significant changes in Lp(a) levels. The impact of interventions that induce substantial weight loss, such as bariatric surgery, on Lp(a) levels is currently unclear. OBJECTIVE: To determine the acute and long-term impact of bariatric surgery on Lp(a) levels in patients with severe obesity. METHODS: Sixty-nine patients with severe obesity underwent biliopancreatic diversion with duodenal switch (BPD-DS) surgery. The lipid profile was evaluated and Lp(a) levels were measured before surgery and at 6 and 12 months after BPD-DS surgery. RESULTS: Median Lp(a) levels at baseline were 11.1 (4.1-41.6) nmol/L. Six months and 12 months after the BDP-DS surgery, we observed an improvement of lipid profile. At 6 months, we observed a 13% decrease in Lp(a) levels (9.7 (2.9-25.6) nmol/L, p < 0.0001) but this decrease was not sustained at 12 months (11.1 (3.9-32.8) nmol/L, p = 0.8). When the patients were separated into tertiles according to Lp(a) levels at baseline, we observed that the Lp(a) reduction at 12 months after BPD-DS surgery remained significant but modest in patients of the top Lp(a) tertile. CONCLUSION: Our results suggest that BPD-DS surgery modestly reduces Lp(a) levels in the short term (6 months) in patients with severe obesity but this improvement is sustained over time only in patients with higher Lp(a) levels.

Impact of a 12-Week Randomized Exercise Training Program on Lipid Profile in Severely Obese Patients Following Bariatric Surgery.

PURPOSE: The benefit of exercise training on lipid profile in bariatric surgery patients is scarce. We assess the effect of a supervised exercise-training program on lipid profile following bariatric surgery. MATERIALS AND METHODS: A total of 60 patients were prospectively recruited, of those 49 completed the study (age 41 ± 11 years; body mass index 45.9 ± 6.1 kg/m2, 75% women). The bariatric surgery procedures performed were sleeve gastrectomy (SG) (n = 24) and biliopancreatic diversion with duodenal switch (BPD-DS) (n = 25). Of the 49 patients who completed the study, 34 had been randomized to a 12-week supervised exercise training program (exercise group) between the 3rd and the 6th month following bariatric surgery (SG = 17 and BPD-DS = 17). Fasting blood samples and anthropometric measurements were performed preoperatively and at 3, 6, and 12 months after bariatric surgery. RESULTS: At 6 months and 12 months, percentage of weight loss was similar between groups (6 months: - 29.6 ± 5.5 vs. - 27.8 ± 7.7%; P = 0.371; 12 months: - 38.4 ± 10.4 vs. - 37.9 ± 9.5%; P = 0.876 exercise vs. control). Both groups had an increase in HDL values between the 3nd and the 6th month following bariatric surgery. There was a significantly greater increment in HDL values in the exercise group (0.18 ± 0.14 vs. 0.07 ± 0.12 mmol/L, P = 0.014; exercise vs. control). CONCLUSION: Our results showed a beneficial effect of a 12-week supervised exercise-training program in bariatric surgery patients showing similar weight loss on HDL-cholesterol levels without additional effect on LDL-cholesterol levels.

Comparison of Short and Long Term Cardiovascular Outcomes After Bariatric Surgery in Patients With vs Without Coronary Artery Disease.

There is little data regarding the risks and benefits of bariatric surgery in patients with coronary artery disease (CAD). We aimed to assess the short- and long-term cardiovascular outcomes of patients with CAD undergoing bariatric surgery. Patients with a history of CAD were identified from a dedicated database with prospectively collected outcomes, comprising all 6795 patients who underwent bariatric surgery between January 1992 and October 2017. Patients were matched with patients who did not have CAD before the bariatric surgery procedure. The primary endpoints were mortality (cardiac and noncardiac) and major adverse cardiocerebral events (MACCE), including all-cause death, myocardial infarction, stroke, and myocardial revascularization at 30 days after bariatric surgery and throughout follow-up. After propensity score matching, 249 patients with chronic CAD were matched with 249 patients without CAD. Throughout follow-up (7.4 years; interquartile range 4.1 to 11.5, maximum 22 years), mortality (mainly cardiac mortality) remained significantly higher in the CAD compared with the non-CAD group (18% vs 10%, hazard ratio [HR] 1.70, 95% confidence interval [CI]: 1.03 to 2.79, p = 0.037). At 30 days, MACCE rate was significantly higher in the CAD compared with the non-CAD group (3.6% vs 0.4%, p = 0.011), essentially driven by non-ST elevation myocardial infarctions. After 30 days, MACCE rates remained significantly higher in the CAD group (30% vs 14%, HR 2.18, 95% CI: 1.45-3.28, p = 0.0002). In conclusion, patients with severe obesity and CAD referred to bariatric surgery were at a higher risk of early and late MACCE compared with non-CAD severely obese patients. Further study is required to define how this cardiovascular risk compares with nonoperated patients.

Methylamine Activates Glucose Uptake in Human Adipocytes Without Overpassing Action of Insulin or Stimulating its Secretion in Pancreatic Islets.

Background: Methylamine, a natural soluble amine present in foods, is known to be a substrate of primary amine oxidase (PrAO) widely expressed in animal tissues. Methylamine has been reported to activate glucose transport in fat cells and to facilitate glucose disposal in rabbits but the interests and limits of such insulin-mimicking actions have not been further explored. This work aimed to perform a preclinical study of the inter-individual variations of these biological properties to study the putative link between PrAO activity and insulin resistance. Methods: Methylamine was tested on human adipocyte preparations and in rabbit pancreatic islets to determine its influence on glucose uptake and insulin release, respectively. PrAO activity and related responses were determined in adipose tissues obtained from two cohorts of non-obese and obese women. Results: Adipose tissue PrAO activity was negatively correlated with insulin resistance in high-risk obese women. PrAO-dependent activation of glucose uptake was negatively correlated with body mass index and reflected the decrease of insulin responsiveness of human fat cells with increasing obesity. Methylamine exhibited antilipolytic properties in adipocytes but was unable to directly activate insulin secretion in isolated pancreatic islets. Conclusions: PrAO activation by its substrates, e.g., methylamine, increases glucose utilization in human adipocytes in a manner that is linked to insulin responsiveness. Methylamine/PrAO interaction can therefore contribute to adipose tissue enlargement but should be considered as potentially useful for diabetes prevention since it could limit lipotoxicity and facilitate glucose handling, at the expense of favoring healthy fat accumulation.

Acute and chronic effect of bariatric surgery on circulating autotaxin levels.

Autotaxin (ATX), an adipose tissue-derived lysophospholipase, has been involved in the pathophysiology of cardiometabolic diseases. The impact of bariatric surgery on circulating ATX levels is unknown. We examined the short- (24 h, 5 days) and longer-term (6 and 12 months) impact of bariatric surgery; as well as the short-term effect of caloric restriction (CR) on plasma ATX levels in patients with severe obesity. We measured ATX levels in 69 men and women (mean age: 41 ± 11 years, body mass index: 49.8 ± 7.1 kg/m2 ), before and after biliopancreatic diversion with duodenal switch surgery (BPD-DS) as well as in a control group (patients with severe obesity without surgery; n = 34). We also measured ATX levels in seven patients with severe obesity and type 2 diabetes who underwent a 3-day CR protocol before their BPD-DS. At baseline, ATX levels were positively associated with body mass index, fat mass, insulin resistance (HOMA-IR) as well as insulin and leptin levels and negatively with fat-free mass. ATX concentrations decreased 26.2% at 24 h after BPD-DS (342.9 ± 152.3 pg/mL to 253.2 ± 68.9 pg/mL, P < 0.0001) and by 16.4% at 12 months after BPD-DS (342.9 ± 152.3 pg/mL to 286.8 ± 182.6 pg/mL, P = 0.04). ATX concentrations were unchanged during follow-up in the control group (P = 0.4), and not influenced by short-term CR. In patients with severe obesity, bariatric surgery induced a rapid and sustained decrease in plasma ATX levels. Acute changes in ATX may not be explained by bariatric surgery-induced CR.

High ApoD protein level in the round ligament fat depot of severely obese women is associated with an improved inflammatory profile.

PURPOSE: Apolipoprotein D (ApoD) is a lipocalin participating in lipid transport. It binds to a variety of ligands, with a higher affinity for arachidonic acid, and is thought to have a diverse array of functions. We investigated a potential role for ApoD in insulin sensitivity, inflammation, and thrombosis-processes related to lipid metabolism-in severely obese women. METHODS: We measured ApoD expression in a cohort of 44 severely obese women including dysmetabolic and non-dysmetabolic patients. Physical and metabolic characteristics of these women were determined from anthropometric measurements and blood samples. ApoD was quantified at the mRNA and protein levels in samples from three intra-abdominal adipose tissues (AT): omental, mesenteric and round ligament (RL). RESULTS: ApoD protein levels were highly variable between AT of the same individual. High ApoD protein levels, particularly in the RL depot, were linked to lower plasma insulin levels (-40%, p = 0.015) and insulin resistance (-47%, p = 0.022), and increased insulin sensitivity (+10%, p = 0.008). Lower circulating pro-inflammatory PAI-1 (-39%, p = 0.001), and TNF-α (-19%, p = 0.030) levels were also correlated to high ApoD protein in the RL AT. CONCLUSIONS: ApoD variability between AT was consistent with different accumulation efficiencies and/or metabolic functions according to the anatomic location of fat depots. Most statistically significant correlations implicated ApoD protein levels, in agreement with protein accumulation in target tissues. These correlations associated higher ApoD levels in fat depots with improved metabolic health in severely obese women.

Long-term follow-up of disease-specific quality of life after bariatric surgery.

BACKGROUND: Substantial improvements in health-related quality of life measured by generic questionnaires (most often the Short Form-36) have been noted over the long term in patients with morbid obesity who had undergone bariatric surgery. OBJECTIVES: To obtain long-term follow-up data on disease-specific quality of life in patients who underwent bariatric surgery (biliopancreatic diversion with duodenal switch) in 2007 to 2008. SETTING: Québec Heart and Lung Institute, Québec, Canada. METHODS: This study is a follow-up of the validation study, the Laval Questionnaire, an obesity-specific measure of health-related quality of life developed to be used in clinical trials. Patients who contributed to the validation study in 2007 to 2008 were administered the Laval Questionnaire again at long-term follow-up. RESULTS: Of 112 patients who contributed to the validation study, 90 were available for this long-term follow-up study (retention rate: 80%). Median follow-up was 8.8 years. For all 6 domains of the Laval Questionnaire, the improvements in quality-of-life scores were much larger than our best estimate of the minimal clinically important difference. In others, we observed some decline in quality-of-life scores over time after initial changes that occurred 1 to 2 years after surgery, during the so-called "honeymoon period." Improvements in quality of life were clearly related to surgery. CONCLUSION: This study confirms that bariatric surgery using biliopancreatic diversion with duodenal switch improves disease-specific quality of life in the short and long term. It also demonstrates that the Laval Questionnaire is responsive to treatment-induced changes.

Acute and Chronic Impact of Bariatric Surgery on Plasma LDL Cholesterol and PCSK9 Levels in Patients With Severe Obesity.

Context: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of low-density lipoprotein cholesterol (LDL-C) concentrations. In patients with severe obesity, biliopancreatic diversion with duodenal switch (BPD-DS) surgery induces substantial weight loss and influences lipoprotein metabolism. The effect of BPD-DS on PCSK9 levels is unknown. Objectives: To determine the acute and chronic impact of BPD-DS on PCSK9 levels and whether the acute impact of BPD-DS could be explained by BPD-DS-associated caloric restriction (CR). Design, Settings, and Participants: PCSK9 levels were measured in 20 men and 49 women (age, 41.5 ± 11.1 years) with severe obesity before, 24 hours, 5 days, and 6 and 12 months after BPD-DS and in a comparable control group (n = 31) at baseline and at 6 and 12 months. PCSK9 levels were also measured during 3-day CR in patients (n = 7) with severe obesity and type 2 diabetes. Results: PCSK9 levels increased 13.4% after 24 hours (248.7 ± 64.8 to 269.7 ± 63.8 ng/mL; P = 0,02) and decreased 9.5% at 12 months compared with baseline (217.6 ± 43.0 ng/mL; P < 0,0001). LDL-C levels decreased 36.2% after 24 hours (2.6 ± 0.7 to 1.7 ± 0.6 mmol/L; P < 0.0001) and 30% at 12 months compared with baseline (1.7 ± 0.5 mmol/L; P < 0.0001). Compared with baseline levels, PCSK9 levels were lower at day 2 but not at day 1 or 3 after CR. Conclusion: BPD-DS is associated with acute increases in PCSK9 levels that do not appear to be explained by CR but may be due to an acute response following surgery. BPD-DS induces chronic reductions in both PCSK9 and LDL-C levels.

Anatomical distribution of primary amine oxidase activity in four adipose depots and plasma of severely obese women with or without a dysmetabolic profile

Semicarbazide-sensitive amine oxidase (SSAO), identical to primary amine oxidase or vascular adhesion protein-1, is a membrane enzyme that generates hydrogen peroxide. SSAO is highly expressed at the adipocyte surface, and its plasma levels increase with type 2 diabetes. Since visceral adipose tissue (AT) is more tightly associated with obesity complications than subcutaneous (SC) abdominal fat, we compared SSAO activity in plasma and 4 distinct AT locations in 48 severely obese women (body mass index (BMI), averaging 54 ± 11 kg/m2), with or without a dysmetabolic profile. Higher glucose and triacylglycerol levels vs lower high-density lipoprotein (HDL)-cholesterol characterized dysmetabolic women (DYS; n = 25) from non-dysmetabolic (NDYS; n = 23), age- and weight-matched subjects. SC, mesenteric (ME), omental (OM), and round ligament (RL) fat locations were collected during bariatric surgery. SSAO capacity to oxidize up to 1 mM benzylamine was determined in AT and plasma with radiometric and fluorimetric methods. Plasma SSAO was higher in the DYS group. SSAO activity was higher in fat than in plasma, when expressed as radiolabeled benzaldehyde per milligram of protein. In ATs from DYS women, protein content was 10 % higher, and basal hydrogen peroxide release lower than in NDYS subjects, except for RL location. The SSAO affinity towards benzylamine did not exhibit regional variation and was not altered by a dysmetabolic profile (K m averaging 184 ± 7 μM; n = 183). Although radiometric and fluorimetric methods gave different estimates of oxidase activity, both indicated that AT SSAO activity did not vary according to anatomical location and/or metabolic status in severely obese women

Bariatric Surgery-Induced Resolution of Hypertension and Obstructive Sleep Apnea: Impact of Modulation of Body Fat, Ectopic Fat, Autonomic Nervous Activity, Inflammatory and Adipokine Profiles.

BACKGROUND: Obesity-associated systemic hypertension (HTN) and obstructive sleep apnea (OSA) have multiple pathophysiological pathways including ectopic fat deposition, inflammation, altered adipokine profile, and increased sympathetic nervous activity. We characterized these potential mechanisms in severely obese patients with or without HTN and OSA. We also compared changes of these mechanisms at 12 months following biliopancreatic diversion with duodenal switch (BPD-DS) surgery according to HTN and OSA resolution. METHODS: Sixty-two severely obese patients were evaluated at baseline and 12 months; 40 patients underwent BPD-DS. Blood samples, bioelectrical impedance analysis, computed tomography scan, and 24-h heart rate monitoring were performed. OSA have been determined with polysomnography and HTN with blood pressure measurement and medical file. RESULTS: Patients with HTN (n = 35) and OSA (n = 32) were older men with higher ectopic fat deposition and lower parasympathetic nervous activity without difference in adipokines and inflammatory markers. Lower reduction in weight was observed in patients with unresolved HTN (-40.9 ± 3.3 kg vs. -55.6 ± 3.8 kg; p = 0.001) and OSA (-41.4 ± 10.7 kg vs. -51.0 ± 15.2 kg; p = 0.006). Visceral adipose tissue reduction was lower in patients with unresolved HTN (-171.0 ± 25.7 cm2 vs. -274.5 ± 29.0 cm2; p = 0.001) in contrast to a trend for lower abdominal subcutaneous adipose tissue reduction in patients with unresolved OSA (-247.7 ± 91.5 cm2 vs. -390.5 ± 109.1 cm2; p = 0.08). At 12 months, parasympathetic activity was lowest in unresolved HTN and OSA patients, without difference in adipokines and inflammatory biomarkers. CONCLUSION: Lower ectopic fat mobilization, lower level of parasympathetic nervous activity, and lower subcutaneous adiposity mobilization may play a role in the pathophysiology of unresolved HTN and OSA following BPD-DS surgery.

Temporal Changes in Gene Expression Profile during Mature Adipocyte Dedifferentiation.

Objective. To characterize changes in gene expression profile during human mature adipocyte dedifferentiation in ceiling culture. Methods. Subcutaneous (SC) and omental (OM) adipose tissue samples were obtained from 4 participants paired for age and BMI. Isolated adipocytes were dedifferentiated in ceiling culture. Gene expression analysis at days 0, 4, 7, and 12 of the cultures was performed using Affymetrix Human Gene 2.0 STvi arrays. Hierarchical clustering according to similarity of expression changes was used to identify overrepresented functions. Results. Four clusters gathered genes with similar expression between day 4 to day 7 but decreasing expression from day 7 to day 12. Most of these genes coded for proteins involved in adipocyte functions (LIPE, PLIN1, DGAT2, PNPLA2, ADIPOQ, CEBPA, LPL, FABP4, SCD, INSR, and LEP). Expression of several genes coding for proteins implicated in cellular proliferation and growth or cell cycle increased significantly from day 7 to day 12 (WNT5A, KITLG, and FGF5). Genes coding for extracellular matrix proteins were differentially expressed between days 0, 4, 7, and 12 (COL1A1, COL1A2, and COL6A3, MMP1, and TGFB1). Conclusion. Dedifferentiation is associated with downregulation of transcripts encoding proteins involved in mature adipocyte functions and upregulation of genes involved in matrix remodeling, cellular development, and cell cycle.

Genetic regulation of differentially methylated genes in visceral adipose tissue of severely obese men discordant for the metabolic syndrome.

A genetic influence on methylation levels has been reported and methylation quantitative trait loci (meQTL) have been identified in various tissues. The contribution of genetic and epigenetic factors in the development of the metabolic syndrome (MetS) has also been noted. To pinpoint candidate genes for testing the association of SNPs with MetS and its components, we aimed to evaluate the contribution of genetic variations to differentially methylated CpG sites in severely obese men discordant for MetS. A genome-wide differential methylation analysis was conducted in visceral adipose tissue (VAT) of 31 severely obese men discordant for MetS (16 with and 15 without MetS) and identified ∼17,800 variable CpG sites. The genome-wide association study conducted to identify the SNPs (meQTL) associated with methylation levels at variable CpG sites revealed 2292 significant associations (P < 2.22 × 10-11) involving 2182 unique meQTLs regulating the methylation levels of 174 variable CpG sites. Two meQTLs disrupting CpG sites located within the collagen-encoding COL11A2 gene were tested for associations with MetS and its components in a cohort of 3021 obese individuals. Rare alleles of these meQTLs showed association with plasma fasting glucose levels. Further analysis conducted on these meQTL suggested a biological impact mediated through the disruption of transcription factor (TF)-binding sites based on the prediction of TF-binding affinities. The current study identified meQTL in the VAT of severely obese men and revealed associations of two COL11A2 meQTL with fasting glucose levels.

Comparison of two methods for measuring 25-OH vitamin D in the follow-up of patients after bilio-pancreatic diversion bariatric surgery.

OBJECTIVE: Our objective was to compare the ECLIA from Roche versus the LC-MS/MS method for quantitation of serum 25-hydroxy-vitamin D in patients who have undergone bariatric surgery. DESIGN AND METHODS: Cross-sectional and correlational studies were performed on three different groups for the 25-OH-D levels quantitated by both methods. The control group of apparently healthy subjects was randomly selected in a clinical chemistry laboratory. Test groups were patients who had undergone bilio-pancreatic diversion (BPD) and were supplemented either with vitamin D2 or with vitamin D3. The number of samples per group was established according to the CLSI recommendation protocol (EPO9-A2-IR). RESULTS: The agreement of LC-MS/MS with the Roche method was acceptable in the apparently healthy subjects group and in the post-BPD D3-supplemented group with an average bias of -1.7% and -9.2%, respectively. However, this agreement was unacceptable in the post-BPD D2-supplemented group with an average bias of -45.3%. The LC-MS/MS enabled us to detect four patients who had excess vitamin D or poisoning with vitamin D for which it was necessary to stop the supplementation with vitamin D in the D2 -supplemented group. CONCLUSION: Despite the apparent good agreement between the Roche method and LC-MS/MS in the healthy subjects group and in the post-DBP D3-supplemented patient group, a considerable bias seems to exist, particularly in the presence of D2. The LC-MS/MS method is therefore the most accurate method to follow the vitamin D2 -supplemented bariatric population.

Anatomical distribution of primary amine oxidase activity in four adipose depots and plasma of severely obese women with or without a dysmetabolic profile.

Semicarbazide-sensitive amine oxidase (SSAO), identical to primary amine oxidase or vascular adhesion protein-1, is a membrane enzyme that generates hydrogen peroxide. SSAO is highly expressed at the adipocyte surface, and its plasma levels increase with type 2 diabetes. Since visceral adipose tissue (AT) is more tightly associated with obesity complications than subcutaneous (SC) abdominal fat, we compared SSAO activity in plasma and 4 distinct AT locations in 48 severely obese women (body mass index (BMI), averaging 54 ± 11 kg/m2), with or without a dysmetabolic profile. Higher glucose and triacylglycerol levels vs lower high-density lipoprotein (HDL)-cholesterol characterized dysmetabolic women (DYS; n = 25) from non-dysmetabolic (NDYS; n = 23), age- and weight-matched subjects. SC, mesenteric (ME), omental (OM), and round ligament (RL) fat locations were collected during bariatric surgery. SSAO capacity to oxidize up to 1 mM benzylamine was determined in AT and plasma with radiometric and fluorimetric methods. Plasma SSAO was higher in the DYS group. SSAO activity was higher in fat than in plasma, when expressed as radiolabeled benzaldehyde per milligram of protein. In ATs from DYS women, protein content was 10 % higher, and basal hydrogen peroxide release lower than in NDYS subjects, except for RL location. The SSAO affinity towards benzylamine did not exhibit regional variation and was not altered by a dysmetabolic profile (K m averaging 184 ± 7 µM; n = 183). Although radiometric and fluorimetric methods gave different estimates of oxidase activity, both indicated that AT SSAO activity did not vary according to anatomical location and/or metabolic status in severely obese women.

Piceatannol and resveratrol share inhibitory effects on hydrogen peroxide release, monoamine oxidase and lipogenic activities in adipose tissue, but differ in their antilipolytic properties.

Piceatannol is a hydroxylated derivative of resveratrol. While both dietary polyphenols coexist in edible plants and fruits, and share equivalent concentrations in several wines, the influence of piceatannol on adiposity has been less studied than that of resveratrol. Though resveratrol is now recognized to limit fat deposition in various obesity models, the benefit of its dietary supplementation remains under debate regarding human obesity treatment or prevention. The research for more potent resveratrol analogs is therefore still undergoing. This prompted us to compare various effects of piceatannol and resveratrol directly on human adipose tissue (hAT). Hydrogen peroxide release was measured by Amplex Red-based fluorescence in subcutaneous hAT samples from obese patients. Interactions of stilbenes with human amine oxidases and quinone reductase were assessed by radiometric methods, computational docking and electron paramagnetic resonance. Influences on lipogenic and lipolytic activities were compared in mouse adipocytes. Resveratrol and piceatannol inhibited monoamine oxidase (MAO) with respective IC50 of 18.5 and 133.7 µM, but not semicarbazide-sensitive amine oxidase (SSAO) in hAT. For both stilbenes, the docking scores were better for MAO than for SSAO. Piceatannol and resveratrol similarly hampered hydrogen peroxide detection in assays with and without hAT, while they shared pro-oxidant activities when incubated with purified quinone reductase. They exhibited similar dose-dependent inhibition of adipocyte lipogenic activity. Only piceatannol inhibited basal and stimulated lipolysis when incubated at a dose ≥100 µM. Thus, piceatannol exerted on fat cells dose-dependent effects similar to those of resveratrol, except for a stronger antilipolytic action. In this regard, piceatannol should be useful in limiting the lipotoxicity related to obesity when ingested or administered alone - or might hamper the fat mobilization induced by resveratrol when simultaneously administered with it.

Biliopancreatic Diversion with Duodenal Switch: Surgical Technique and Perioperative Care.

The goal of this article is to present an overview of selection criteria, surgical technique, and perioperative outcomes of biliopancreatic diversion with duodenal switch. The standard follow-up requirements, including vitamin supplementation, and long-term risks associated with metabolic surgery are also discussed. Most of the data reported here are based on the authors' experience with 4000 biliopancreatic diversions with duodenal switch performed in their institution since 1990.