Regulation of angiopoietin-like 4 and lipoprotein lipase in human adipose tissue

Background: Elevated plasma triglycerides are increasingly viewed as a causal risk factor for coronary artery disease. One protein that raises plasma triglyceride levels and that has emerged as a modulator of coronary artery disease risk is angiopoietin-like 4 (ANGPTL4). ANGPTL4 raises plasma triglyceride levels by inhibiting lipoprotein lipase (LPL), the enzyme that catalyzes the hydrolysis of circulating triglycerides on the capillary endothelium. Objective: The objective of the present study was to assess the association between ANGPTL4 and LPL in human adipose tissue, and to examine the influence of nutritional status on ANGPTL4 expression. Methods: We determined ANGPTL4 and LPL mRNA and protein levels in different adipose tissue depots in a large number of severely obese patients who underwent bariatric surgery. Furthermore, in 72 abdominally obese subjects, we measured ANGPTL4 and LPL mRNA levels in subcutaneous adipose tissue in the fasted and postprandial state. Results: ANGPTL4 mRNA levels were highest in subcutaneous adipose tissue, whereas LPL mRNA levels were highest in mesenteric adipose tissue. ANGPTL4 and LPL mRNA levels were strongly positively correlated in the omental and subcutaneous adipose tissue depots. In contrast, ANGPTL4 and LPL protein levels were negatively correlated in subcutaneous adipose tissue, suggesting a suppressive effect of ANGPTL4 on LPL protein abundance in subcutaneous adipose tissue. ANGPTL4 mRNA levels were 38% higher in the fasted compared to the postprandial state. Conclusion: Our data provide valuable insights into the relationship between ANGPTL4 and LPL in human adipose tissue, as well as the physiological function and regulation of ANGPTL4 in humans

Health-related quality of life after sleeve gastrectomy equal to Roux-en-Y gastric bypass patients?

Purpose: Sleeve gastrectomy (SG) is the most popular type of bariatric surgery. It has often been compared to Roux-en-Y gastric bypass (RYGB) in terms of clinical outcomes. However, health-related quality of life (HRQoL) has been sparsely studied after SG. The goal was to study HRQoL after SG using a generic (RAND-36) and an obesity-specific (impact of weight on quality of life-lite, IWQOL-lite) questionnaire and to compare the results with RYGB. Methods: HRQoL and weight were measured before and 9, 15, and 24 months after surgery. RAND-36 physical health summary (PHS) and mental health summary (MHS), and IWQOL-lite total score were calculated. A mixed model analysis was conducted to study the change in HRQoL and compare SG with RYGB. Results: A total of 219 patients (8.7%) underwent a SG and 2309 patients (91.3%) a RYGB. PHS, MHS, and IWQOL-lite significantly improved after SG when comparing baseline to all follow-up moments (p < 0.001 in all). There were no significant differences when comparing SG with RYGB: change in PHS (β − 0.10, 95% CI − 1.24 to 1.04, p = 0.861), MHS (β − 0.51, 95% CI − 1.56 to 0.52, p = 0.330), and IWQOL-lite (β 0.310, 95% CI − 0.85 to 1.47, p = 0.601). Conclusion: HRQoL significantly improved after SG. In the included populations, weight loss was comparable and the extent to which HRQoL improved did not differ between SG and RYGB, when measured with the RAND-36 or IWQOL-lite. This might be partly caused by the fact that these questionnaires do not assess specific bariatric HRQoL and/or complaints

Definitions of Long-Term Weight Regain and Their Associations with Clinical Outcomes

Introduction: The prevalence and clinical significance of weight regain after bariatric surgery remains largely unclear due to the lack of a standardized definition of significant weight regain. The development of a clinically relevant definition of weight regain requires a better understanding of its clinical significance. Objectives: To assess rates of weight regain 5 years after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), applying six definitions and investigating their association with clinical outcomes. Methods: Patients were followed up until 5 years after surgery and weight regain was calculated. Regression techniques were used to assess the association of weight regain with health-related quality of life (HRQoL) and the presence of comorbidities. Results: A total of 868 patients participated in the study, with a mean age of 46.6 (± 10.4) years, of which 79% were female. The average preoperative BMI was 44.8 (± 5.9) kg/m2 and the total maximum weight loss was 32% (± 8%). Eighty-seven percent experienced any regain. Significant weight regain rates ranged from 16 to 37% depending on the definition. Three weight regain definitions were associated with deterioration in physical HRQoL (p < 0.05), while associations between definitions of weight regain and the presence of comorbidities 5 years after surgery were not significant. Conclusion: These results indicate that identifying one single categorical definition of clinically significant weight regain is difficult. Additional research into the clinical significance of weight regain is needed to inform the development of a standardized definition that includes all dimensions of surgery success: weight, HRQoL, and comorbidity remission

Early Postoperative Weight Loss Predicts Weight Loss up to 5 Years After Roux-En-Y Gastric Bypass, Banded Roux-En-Y Gastric Bypass, and Sleeve Gastrectomy

PURPOSE: Previous studies showed that patients with lower weight loss after bariatric surgery could be identified based on early postoperative weight loss. However, these studies had only 12-36-month follow-up. This study aimed to explore whether patients in the lowest weight loss quartile at 3 months had lower weight loss trajectories up to 5 years after Roux-en-Y gastric bypass (RYGB), banded Roux-en-Y gastric bypass (BRYGB), and sleeve gastrectomy (SG) surgery. METHODS: Weight was assessed preoperatively, and 3, 6, 9, 12, 24, 36, 48, and 60 months postoperatively. Patients were grouped into four categories based on quartiles of percentage total weight loss (%TWL) at 3-month follow-up. Results were compared between the lowest %TWL quartile group and other quartile groups. RESULTS: Patients underwent either RYGB (n=13,106; 72%), SG (n=3585; 20%), or BRYGB (n=1391, 8%) surgery. Weight loss trajectories of patients in the lowest %TWL quartile group remained lower than that of other quartile groups throughout a 5-year follow-up, for all three types of surgery. Patients in the lowest %TWL quartile group had higher age at surgery, higher baseline BMI, and were more likely to be male (in the SG group), and to suffer from diabetes, hypertension, dyslipidemia, and osteoarthritis. CONCLUSION: This study showed a positive association between weight loss at 3 and 12 to 60 months after bariatric surgery. Weight loss at 3 months after surgery could be used to identify patients whose anticipated weight loss trajectories are below average, to potentially improve their outcomes through early behavioral or medical interventions

Five-year weight loss, physical activity, and eating style trajectories after bariatric surgery

BACKGROUND: Little research has taken individual variability in weight loss into account. Furthermore, physical activity (PA) and eating style (ES) have been linked only sporadically to weight loss longitudinally. OBJECTIVES: Identify and describe latent classes of weight loss, change of PA, and change of ES up to 5 years after surgery and investigate whether these trajectories are interrelated. SETTING: Multicenter outpatient clinic. METHODS: This is a retrospective study of data collected during standard treatment before and up to 5 years after surgery. Latent class growth analysis was used to identify trajectories of weight loss (percent total weight loss), PA (Baecke questionnaire), and ES (Dutch Eating Behavior Questionnaire). RESULTS: A total of 2785 patients were included. Follow-up rate was 84% at 1 year and 34% at 5 years. Analyses revealed 5 weight loss trajectories. Most patients followed an average, fairly stable weight loss trajectory (48%) or an above-average partial-regain trajectory (36%). Other patients followed a low-responder trajectory (9%), a rapid weight loss and weight regain trajectory (6%), or a continued weight loss trajectory (2%). Patients in the most favorable weight loss trajectory were more likely to also follow the most favorable ES trajectories. Patients following the most unfavorable weight loss trajectory were never also in the PA trajectory with an initial great increase in PA. CONCLUSION: This study distinguishes demographic and behavioral factors that may influence long-term weight loss trajectories after bariatric surgery. Trajectories varied mainly in magnitude and less in the pattern of weight loss over time, suggesting that very deviant patterns are rare

Genetic analysis in the bariatric clinic; impact of a PTEN gene mutation

Background: Pathogenic PTEN gene mutations are known to cause PTEN tumor hamartoma syndrome. Recent studies also suggest a role for PTEN mutations in the pathogenesis of obesity. No PTEN mutations have been reported among bariatric surgery patients and obesity treatment results are unknown. Since preventive screening for associated tumors is offered to patients with molecular proven PTEN hamartoma tumor syndrome, recognition of this condition in the bariatric surgery clinic is important. Method: We present a patient with morbid obesity who carries a known pathogenic PTEN mutation, identified at the bariatric surgery clinic using an obesity gene panel consisting of 52 obesity–associated genes. We analyzed the weight loss response during the first 3 years after Sleeve Gastrectomy. Results: At 1, 2 and 3 years after surgery, the patient achieved a Total Body Weight Loss of 39.4%, 48.8% and 44.9%, respectively. This corresponds to the results of a control group of 18 female patients with normal genetic test results. Conclusion: Our patient illustrates the importance of recognizing this serious genetic condition for which preventive cancer screening options are available. The positive weight loss results after Sleeve Gastrectomy suggest that this could be a successful treatment option for obesity patients with PTEN mutations

Altered neural responsivity to food cues in relation to food preferences, but not appetite-related hormone concentrations after RYGB-surgery

Background: After Roux-en-Y gastric bypass (RYGB) surgery, patients report a shift in food preferences away from high-energy foods. Objective: We aimed to elucidate the potential mechanisms underlying this shift in food preferences by assessing changes in neural responses to food pictures and odors before and after RYGB. Additionally, we investigated whether altered neural responsivity was associated with changes in plasma endocannabinoid and ghrelin concentrations. Design: 19 RYGB patients (4 men; age 41 ± 10 years; BMI 41 ± 1 kg/m2 before; BMI 36 ± 1 kg/m2 after) participated in this study. Before and two months after RYGB surgery, they rated their food preferences using the Macronutrient and Taste Preference Ranking Task and BOLD fMRI responses towards pictures and odors of high-, and low-energy foods and non-food items were measured. Blood samples were taken to determine plasma endocannabinoid and ghrelin concentrations pre- and post-surgery. Results: Patients demonstrated a shift in food preferences away from high-fat/sweet and towards low-energy/savory food products, which correlated with decreased superior parietal lobule responsivity to high-energy food odor and a reduced difference in precuneus responsivity to high-energy versus low-energy food pictures. In the anteroventral prefrontal cortex (superior frontal gyrus) the difference in deactivation towards high-energy versus non-food odors reduced. The precuneus was less deactivated in response to all cues. Plasma concentrations of anandamide were higher after surgery, while plasma concentrations of other endocannabinoids and ghrelin did not change. Alterations in appetite-related hormone concentrations did not correlate with changes in neural responsivity. Conclusions: RYGB leads to changed responsivity of the frontoparietal control network that orchestrates top-down control to high-energy food compared to low-energy food and non-food cues, rather than in reward related brain regions, in a satiated state. Together with correlations with the shift in food preference from high- to low-energy foods this indicates a possible role in new food preference formation.</p

Diagnosing internal herniation after Roux-en-Y gastric bypass surgery: Literature overview, cadaver study and the added value of 3D CT angiography

Purpose The purposes of the study are to outline the complexity of diagnosing internal herniation after Roux-en-Y gastric bypass (RYGB) surgery and to investigate the added value of computed tomography angiography (CTA) for diagnosing internal herniation. Materials and Methods A cadaver study was performed to investigate the manifestations of internal hernias and mesenteric vascularization. Furthermore, a prospective, ethics approved study with retrospective interpretation was conducted. Ten patients, clinically suspected for internal herniation, were prospectively included. After informed consent was obtained, these subjects underwent abdominal CT examination, including additional arterial phase CTA. All subjects underwent diagnostic laparoscopy for suspected internal herniation. The CTA was used to create a 3D reconstruction of the mesenteric arteries and surgical staples (3D CTA). The 3D CTA was interpreted, taking into account the presence and type of internal hernia that was found upon laparoscopy. Results Cadaveric analysis demonstrated the complexity of internal herniation. It also confirmed the expected changes in vascular structure and surgical staple arrangement in the presence of internal herniation. 3D CTA studies of the subjects with active internal hernias demonstrated remarkable differences when compared to control 3D CTA studies. The blood supply of herniated intestinal limbs in particular showed abnormal trajectories. Additionally, enteroenterostomy staple lines had migrated or altered orientation. Conclusion 3D CTA is a promising technique for diagnosing active internal hernias. Our findings suggest that for diagnosing internal hernias, focus should probably shift from routine abdominal CT examination towards the 3D assessment of the mesenteric vasculature and surgical staples