Do Gut Hormones Contribute to Weight Loss and Glycaemic Outcomes after Bariatric Surgery?

Bariatric surgery is an effective intervention for management of obesity through treating dysregulated appetite and achieving long-term weight loss maintenance. Moreover, significant changes in glucose homeostasis are observed after bariatric surgery including, in some cases, type 2 diabetes remission from the early postoperative period and postprandial hypoglycaemia. Levels of a number of gut hormones are dramatically increased from the early period after Roux-en-Y gastric bypass and sleeve gastrectomy-the two most commonly performed bariatric procedures-and they have been suggested as important mediators of the observed changes in eating behaviour and glucose homeostasis postoperatively. In this review, we summarise the current evidence from human studies on the alterations of gut hormones after bariatric surgery and their impact on clinical outcomes postoperatively. Studies which assess the role of gut hormones after bariatric surgery on food intake, hunger, satiety and glucose homeostasis through octreotide use (a non-specific inhibitor of gut hormone secretion) as well as with exendin 9-39 (a specific glucagon-like peptide-1 receptor antagonist) are reviewed. The potential use of gut hormones as biomarkers of successful outcomes of bariatric surgery is also evaluated

Can Weight Loss Improve the Cardiovascular Outcomes of Patients with Obesity and Obstructive Sleep Apnea?

Cardiovascular events are the primary cause of mortality in patients with obstructive sleep apnea and obesity. The rising prevalence of obstructive sleep apnea in recent decades has been linked to increasing rates of obesity. Obstructive sleep apnea has also been linked with many different cardiovascular diseases including coronary artery disease, stroke, heart failure, hypertension, and atrial fibrillation. Obesity is an increasing health concern globally, in part because obesity complications such as hypertension, diabetes, and obstructive sleep apnea increase the risk of cardiovascular diseases. More than 10% weight loss may be required to prevent or reverse obesity complications. Treatment approaches to obesity include nutritional therapy, exercise therapy, pharmacotherapy, and surgical therapies. This review intends to identify the effects of weight loss on cardiovascular outcomes in patients with obesity and obstructive sleep apnea. Despite the strong association between cardiovascular diseases and obstructive sleep apnea, randomized trials have failed to demonstrate that treatment of obstructive sleep apnea reduces cardiovascular events, even in patients with established cardiovascular diseases. Weight loss in patients with obstructive sleep apnea improves HbA1c, systolic blood pressure, HDL cholesterol, and triglycerides, but thus far no changes in cardiovascular events have been shown. The combination of weight loss with continuous positive airway pressure (CPAP) appears more beneficial than either treatment in isolation. Large well-controlled trials in patients with obstructive sleep apnea to assess the effects of different weight reduction programs on cardiovascular disease are still needed

Pharmacological profile of once-weekly injectable semaglutide for chronic weight management

Introduction: The recent approval in the USA (Food and Drug Administration), Canada (Health Canada), UK (Medicines and Healthcare products Regulatory Agency), and EU (European Medicines Agency) of once-weekly injectable semaglutide 2.4 mg, as an adjunct to a calorie-controlled diet and increased physical activity, for chronic weight management provides health-care practitioners with an additional option when prescribing weight-loss medication. Areas covered: We describe the chemistry, mechanism of action, and pharmacological properties of semaglutide (a glucagon-like peptide 1 receptor agonist [GLP-1 RA]) and discuss clinical data and considerations for using once-weekly subcutaneous semaglutide 2.4 mg as treatment for overweight and obesity among patients with and without type 2 diabetes (T2D). Expert opinion: Once-weekly subcutaneous semaglutide 2.4 mg is the most efficacious medication approved for chronic weight management among patients with overweight and obesity, with and without T2D, and is the first drug to induce sustained double-digit reductions in percentage body weight over 1- to 2-year treatment periods. It demonstrates a similar safety and tolerability profile to other GLP-1 RAs. Semaglutide 2.4 mg treatment could dramatically improve clinical approaches to weight management, but the relatively high cost might prevent patients accessing treatment. Further research exploring the cost-effectiveness of subcutaneous semaglutide 2.4 mg is required

Mechanisms of weight loss after obesity surgery

Obesity surgery remains the most effective treatment for obesity and its complications. Weight loss was initially attributed to decreased energy absorption from the gut but have since been linked to reduced appetitive behaviour and potentially increased energy expenditure. Implicated mechanisms associating rearrangement of the gastrointestinal tract with these metabolic outcomes include central appetite control, release of gut peptides, change in microbiota and bile acids. However, the exact combination and timing of signals remain largely unknown. In this review, we survey recent research investigating these mechanisms, and seek to provide insights on unanswered questions over how weight loss is achieved following bariatric surgery which may eventually lead to safer, nonsurgical weight-loss interventions or combinations of medications with surger

New therapies for obesity

Obesity is a chronic disease associated with serious complications and increased mortality. Weight loss through lifestyle changes results in modest weight loss long-term possibly due to compensatory biological adaptations (increased appetite and reduced energy expenditure) promoting weight gain. Bariatric surgery was until recently the only intervention that consistently resulted in ≥ 15% weight loss and maintenance. Our better understanding of the endocrine regulation of appetite has led to the development of new medications over the last decade for treatment of obesity with main target the reduction of appetite. The efficacy of semaglutide 2.4 mg/week - the latest glucagon like peptide-1 (GLP-1) receptor analogue - on weight loss for people with obesity suggests that we are entering a new era in obesity pharmacotherapy where ≥15% weight loss is feasible. Moreover, the weight loss achieved with the dual agonist tirzepatide (GLP-1/glucose-dependent insulinotropic polypeptide) for people with type 2 diabetes and most recently also obesity, indicate that combining the GLP-1 with other gut hormones may lead to additional weight loss compared to GLP-1 receptor analogues alone and in the future, multi-agonist molecules may offer the potential to bridge further the efficacy gap between bariatric surgery and the currently available pharmacotherapies. This article provides a review of the currently available interventions for weight loss and weight maintenance with a focus on pharmacological therapies for obesity approved over the last decade, as well as the emerging development of new obesity pharmacotherapies.</p

Meal Patterns and Food Choices of Female Rats Fed a Cafeteria-Style Diet Are Altered by Gastric Bypass Surgery

After Roux-en-Y gastric bypass surgery (RYGB), rats tend to reduce consumption of high-sugar and/or high-fat foods over time. Here, we sought to investigate the behavioral mechanisms underlying these intake outcomes. Adult female rats were provided a cafeteria diet comprised of five palatable foodstuffs varying in sugar and fat content and intake was monitored continuously. Rats were then assigned to either RYGB, or one of two control (CTL) groups: sham surgery or a nonsurgical control group receiving the same prophylactic iron treatments as RYGB rats. Post-sur-gically, all rats consumed a large first meal of the cafeteria diet. After the first meal, RYGB rats reduced intake primarily by decreasing the meal sizes relative to CTL rats, ate meals more slowly, and displayed altered nycthemeral timing of intake yielding more daytime meals and fewer nighttime meals. Collectively, these meal patterns indicate that despite being motivated to consume a cafeteria diet after RYGB, rats rapidly learn to modify eating behaviors to consume foods more slowly across the entire day. RYGB rats also altered food preferences, but more slowly than the changes in meal patterns, and ate proportionally more energy from complex carbohydrates and protein and proportionally less fat. Overall, the pattern of results suggests that after RYGB rats quickly learn to adjust their size, eating rate, and distribution of meals without altering meal number and to shift their macronutrient intake away from fat; these changes appear to be more related to postingestive events than to a fundamental decline in the palatability of food choices