Various bariatric surgical procedures are effective at improving health in patients with obesity associated co-morbidities, but the aim of this review is to specifically describe the mechanisms ...through which Roux-en-Y gastric bypass (RYGB) surgery enables weight loss for obese patients using observations from both human and animal studies. Perhaps most but not all clinicians would agree that the beneficial effects outweigh the harm of RYGB; however, the mechanisms for both the beneficial and deleterious (for example postprandial hypoglycaemia, vitamin deficiency and bone loss) effects are ill understood. The exaggerated release of the satiety gut hormones, such as GLP-1 and PYY, with their central and peripheral effects on food intake has given new insight into the physiological changes that happen after surgery. The initial enthusiasm after the discovery of the role of the gut hormones following RYGB may need to be tempered as the magnitude of the effects of these hormonal responses on weight loss may have been overestimated. The physiological changes after RYGB are unlikely to be due to a single hormone, or single mechanism, but most likely involve complex gut-brain signalling. Understanding the mechanisms involved with the beneficial and deleterious effects of RYGB will speed up the development of effective, cheaper and safer surgical and non-surgical treatments for obesity.
BACKGROUND AND PURPOSE The glucagon‐like peptides GLP‐1 and GLP‐2 are secreted from enteroendocrine L‐cells following nutrient ingestion. Drugs that increase activity of the GLP‐1 axis are highly ...successful therapies for type 2 diabetes, and boosting L‐cell secretion is a potential strategy for future diabetes treatment. The aim of the present study was to further our understanding of the bile acid receptor GPBA (TGR5), an L‐cell target currently under therapeutic exploration.
EXPERIMENTAL APPROACH GLUTag cells and mixed primary murine intestinal cultures were exposed to bile acids and a specific agonist, GPBAR‐A. Secretion was measured using hormone assays and intracellular calcium and cAMP responses were monitored using real‐time imaging techniques.
KEY RESULTS Bile acid‐triggered GLP‐1 secretion from GLUTag cells was GPBA‐dependent, as demonstrated by its abolition following tgr5 siRNA transfection. Bile acids and GPBAR‐A increased GLP‐1 secretion from intestinal cultures, with evidence for synergy between the effects of glucose and GPBA activation. Elevation of cAMP was observed following GPBA activation in individual GLUTag cells. Direct calcium responses to GPBAR‐A were small, but in the presence of the agonist, a subpopulation of cells that was previously poorly glucose‐responsive exhibited robust glucose responses. In vivo, increased delivery of bile to more distal regions of the ileum augmented L‐cell stimulation.
CONCLUSIONS AND IMPLICATIONS GPBA signalling in L‐cells involves rapid elevation of cAMP, and enhanced calcium and secretory responses to glucose. Modulation of this receptor therapeutically may be an attractive strategy to enhance GLP‐1 secretion and achieve better glycaemic control in diabetic patients.
Abstract Roux-en-Y gastric bypass (gastric bypass) patients reportedly have changes in perception and consumption of sweet-tasting foods. This study aimed to further investigate alterations in sweet ...food intake in rats and sucrose detection in humans after gastric bypass. Wistar rats were randomized to gastric bypass or sham-operations and preference for sucrose (sweet), sodium chloride (salty), citric acid (sour) and quinine hydrochloride (bitter) was assessed with standard two-bottle intake tests (vs. water). Intestinal T1R2 and T1R3 expression and plasma levels of glucagon-like-peptide 1 (GLP-1) and peptide YY (PYY) were measured. Furthermore, obese patients and normal weight controls were tested for sucrose taste detection thresholds pre- and postoperatively. Visual analogue scales measuring hedonic perception were used to determine the sucrose concentration considered by patients and controls as “just about right” pre- and postoperatively. Gastric bypass reduced the sucrose intake relative to water in rats (p < 0.001). Preoperative sucrose exposure reduced this effect. Preference or aversion for compounds representative of other taste qualities in naïve rats remained unaffected. Intestinal T1R2 and T1R3 expression was significantly decreased in the alimentary limb while plasma levels of GLP-1 and PYY were elevated after bypass in rats (p = 0.01). Bypass patients showed increased taste sensitivity to low sucrose concentrations compared with controls (p < 0.05), but both groups considered the same sucrose concentration as “just about right” postoperatively. In conclusion, gastric bypass reduces sucrose intake relative to water in sucrose-naïve rats, but preoperative sucrose experience attenuates this effect. Changes in sucrose taste detection do not predict hedonic taste ratings of sucrose in bypass patients which remain unchanged. Thus, factors other than the unconditional affective value of the taste may also play a role in determining food preferences after gastric bypass.
Bariatric surgery reduces incidence of albuminuria and end-stage renal disease in patients with obesity. Effects of bariatric surgery on long-term remission and progression of pre-existing ...obesity-related renal damage are mainly unexplored. Here we investigate the long-term effects of bariatric surgery compared with conventional obesity care on remission and progression of albuminuria.
4047 patients were included in the Swedish Obese Subjects study. Inclusion criteria were age 37-60 years, BMI ≥ 34 kg/m
in men and BMI ≥ 38 kg/m
in women. Our analysis comprised 803 patients (19.8% of total population, 357 control, 446 surgery) with pre-existing albuminuria including 693 patients (312 control, 381 surgery) with microalbuminuria, and 110 patients (45 control, 65 surgery) with macroalbuminuria. Surgery patients were treated with banding, vertical banded gastroplasty, or gastric bypass. Control patients received conventional obesity care.
Total urinary albumin excretion was 36.5% lower in all patients with albuminuria after 15 years, 44.5% lower in patients with microalbuminuria after 15 years, and 27.8% lower in patients with macroalbuminuria after 2 years following bariatric surgery compared with conventional care. In surgery patients with microalbuminuria, remission to normoalbuminuria was higher (OR, 5.9, 2.2, 3.2, p < 0.001) and progression to macroalbuminuria was lower (OR, 0.28, 0.26, 0.25, p ≤ 0.02) at 2, 10, and 15 years, respectively, compared with control patients. In surgery patients with macroalbuminuria remission to normo- or microalbuminuria was higher (OR, 3.67, p = 0.003) after 2 years. No differences between surgery and control patients with macroalbuminuria were observed after 10 and 15 years. Surgery slowed progression of eGFR decline after 2 years in patients with microalbuminuria and macroalbuminuria (treatment effect: 1.0 ml/min/1.73 m
/year, p = 0.001 and 1.4 ml/min/1.73 m
/year, p = 0.047, respectively).
Bariatric surgery had better effects than conventional obesity care on remission of albuminuria and prevention of eGFR decline, indicating that patients with obesity-related renal damage benefit from bariatric surgery.
Environmental conditions and plant size may both alter the outcome of inter-specific plant– plant interactions, with seedlings generally facilitated more strongly than larger individuals in stressful ...habitats. However, the combined impact of plant size and environmental severity on interactions is poorly understood.
Here, we tested explicitly for the first time the hypothesis that ontogenetic shifts in interactions are delayed under increasingly severe conditions by examining the interaction between a grass, Agrostis magellanica, and a cushion plant, Azorella selago, along two severity gradients.
The impact of A. selago on A. magellanica abundance, but not reproductive effort, was related to A. magellanica size, with a trend for delayed shifts towards more negative interactions under greater environmental severity. Intermediate-sized individuals were most strongly facilitated, leading to differences in the size-class distribution of A. magellanica on the soil and on A. selago. The A. magellanica size-class distribution was more strongly affected by A. selago than by environmental severity, demonstrating that the plant–plant interaction impacts A. magellanica population structure more strongly than habitat conditions.
As ontogenetic shifts in plant–plant interactions cannot be assumed to be constant across severity gradients and may impact species population structure, studies examining the outcome of interactions need to consider the potential for size- or age-related variation in competition and facilitation.
Gastric bypass surgery (GBP) leads to sustained weight loss and significant improvement in type 2 diabetes (T2DM). Bile acids (BAs), signaling molecules which influence glucose metabolism, are a ...potential mediator for the improvement in T2DM after GBP. This study sought to investigate the effect of GBP on BA levels and composition in individuals with T2DM.
Plasma BA levels and composition and fibroblast growth factor (FGF)-19 levels were measured during fasting and in response to an oral glucose load before and at 1 month and 2 years post GBP in 13 severely obese women with T2DM.
A striking temporal change in BA levels and composition was observed after GBP. During the fasted state, BA concentrations were generally reduced at 1 month, but increased 2 years post GBP. Postprandial BA levels were unchanged 1 month post GBP, but an exaggerated postprandial peak was observed 2 years after the surgery. A significant increase in the 12α-hydroxylated/non12α-hydroxylated BA ratio during fasting and postprandially at 2 years, but not 1 month, post GBP was observed. Significant correlations between BAs vs FGF-19, body weight, the incretin effect and peptide YY (PYY) were also found.
This study provides evidence that GBP temporally modifies the concentration and composition of circulating BAs in individuals with T2DM, and suggests that BAs may be linked to the improvement in T2DM after GBP.
•Physico-chemical characterization of nanotalcs.•Nanostructuring of new synthetic nanotalc in polyamide 6 and polypropylene matrices.•Improvement of thermal and mechanical properties of ...nanocomposites.
New layered synthetic nanotalc prepared at a lab-scale by a conventional hydrothermal process and commercial natural fine talc were used in order to establish a comparative study in terms of their contributions on the improvement of the final properties of two different polymers: a nonpolar polyolefin matrix and a polyamide. All samples were prepared by melt extrusion in a co-rotating microcompounder. The surface properties of talc – surface energy and isoelectric point – were probed. The particles’ crystalline structure and the distribution/dispersion within the polymer matrix were performed using transmission electron microscopy and X-ray diffraction. The effect of talc particles on the crystallinity, the thermal and mechanical properties was highlighted as a function of the surface properties of talc. In the case of talc-filled PP systems, it seems that the incorporation of both natural and synthetic talc greatly improves the thermal stability of polypropylene matrix. The highest elastic modulus was obtained in presence of highly nucleating natural talc. Oppositely, the best ductility was observed for the synthetic talc-filled PP systems. For PA6/talc nanocomposites, a remarkable improvement in the dispersion of talc layers was shown and a significant increase in Young’s modulus was determined due to the closer affinity between the hydrophilic nanotalc lamellae and the polar PA6 matrix.
Obesity is recognized as a global health crisis. Bariatric surgery offers a treatment that can reduce weight, induce remission of obesity-related diseases, and improve the quality of life. In this ...article, we outline the different options in bariatric surgery and summarize the recommendations for selecting and assessing potential candidates before proceeding to surgery. We present current data on post-surgical outcomes and evaluate the psychosocial and economic effects of bariatric surgery. Finally, we evaluate the complication rates and present recommendations for post-operative care.
The number of bariatric surgical procedures performed has increased dramatically. This review discusses the clinical and physiological changes, and in particular, the mechanisms behind weight loss ...and glycaemic improvements, observed following the gastric bypass, sleeve gastrectomy and gastric banding bariatric procedures. The review then examines how close we are to mimicking the clinical or physiological effects of surgery through less invasive and safer modern interventions that are currently available for clinical use. These include dietary interventions, orlistat, lorcaserin, phentermine/topiramate, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, pramlintide, dapagliflozin, the duodenal-jejunal bypass liner, gastric pacemakers and gastric balloons. We conclude that, based on the most recent trials, we cannot fully mimic the clinical or physiological effects of surgery; however, we are getting closer. A 'medical bypass' may not be as far in the future as we previously thought, as the physician's armamentarium against obesity and type 2 diabetes has recently got stronger through the use of specific dietary modifications, novel medical devices and pharmacotherapy. Novel therapeutic targets include not only appetite but also taste/food preferences, energy expenditure, gut microbiota, bile acid signalling, inflammation, preservation of β-cell function and hepatic glucose output, among others. Although there are no magic bullets, an integrated multimodal approach may yield success. Non-surgical interventions that mimic the metabolic benefits of bariatric surgery, with a reduced morbidity and mortality burden, remain tenable alternatives for patients and health-care professionals.
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