Long-term Treatment Of Obesity Research Articles

The effectiveness and sustainability of health outcomes from a holistic digital weight-loss service with concomitant initiation of tirzepatide: A pragmatic randomized controlled trial in the UK.

To measure the effectiveness and sustainability of the Juniper UK digital weight-loss service (DWLS), which delivers 6 months of personalized, proactive lifestyle coaching supplemented with tirzepatide to patients through a multidisciplinary team (MDT). An observer-blinded randomized controlled trial (RCT) will be conducted on a cohort of non-diabetic patients of the Juniper DWLS in the UK. Participants in both the intervention and control groups will receive weekly subcutaneous injections of 2.5 mg tirzepatide for 4 weeks, uptitrating the dose to 5.0 mg from weeks 5 to 8, and by 2.5 mg every 4 weeks until reaching 15 mg in week 21, which they will maintain until the end of the intervention period at 6 months, when participants will be taken off the medication. The intervention group will receive personalized weeklylifestyle coaching with a focus on protein intake and resistance training for 6 months. Participants in the control group will attend a diet and exercise group counselling session at programme inception and will be sent a summary of the session's content at months 2 and 4. Aside from these events, health coaches will only interact with control group participants on a reactive basis. From month 6 to month 12, participants from both groups will no longer have access to their MDTs. The trial's co-primary endpoints include weight loss, fat-free to fat-mass ratio and composite strength measures at 12 months (6 months following the end of treatment), compared with baseline. Secondary endpoints include percentage change in weight, fat-free to fat-mass ratio, and composite strength from baseline to 6 months, side effect incidence, and change in cardiometabolic risk factors at 12 months. Quality of life and programme engagement represent the study's exploratory endpoints. A total of 688 participants enrolled in the study, with a mean age of 44.6 (± 11.4) years and a mean body mass index of 34.8 (± 7.5) kg/m2; 81.0% of participants are women, and 72.8% are of White ethnicity. More than three-quarters of participants have at least one co-morbidity, with dyslipidaemia (42.4%), hypertension (35.3%) and high cholesterol (31.8%) being the most prevalent conditions. This RCT will be the first to assess the effectiveness and sustainability of a real-world intensive, multidisciplinary DWLS, and it should highlight the potential of such a service for long-term obesity treatment compared with programmes that deliver standard health counselling.

Antiobesity pharmacotherapy to facilitate living kidney donation

Obesity is a chronic, relapsing disease that increases the risks of living kidney donation; at the same time, transplant centers have liberalized body mass index constraints for donors. With the increasing number of antiobesity medications available, the treatment of obesity with antiobesity medications may increase the pool of potential donors and enhance donor safety. Antiobesity medications are intended for long-term use given the chronic nature of obesity. Cessation of treatment can be expected to lead to weight regain and increase the risk of comorbidity rebound/development. In addition, antiobesity medications are meant to be used in conjunction with—rather than in replacement of—diet and physical activity optimization. Antiobesity medication management includes selecting medications that may ameliorate any coexisting medical conditions, avoiding those that are contraindicated in such conditions, and being sensitive to any out-of-pocket expenses that may be incurred by the potential donor. A number of questions remain regarding who will and should shoulder the costs of long-term obesity treatment for donors. In addition, future studies are needed to quantify the degree of weight loss and duration of weight loss maintenance needed to normalize the risk of adverse kidney outcomes relative to comparable nondonors and lower-weight donors.

Aqueous remote loading of setmelanotide in poly(lactic-co-glycolic acid) microspheres for long-term obesity treatment

Setmelanotide (Imcivree™) was developed as a daily injectable therapeutic peptide for the treatment of rare forms of syndromic obesity, such as POMC deficiency and leptin receptor deficiency. The important option of poly(lactic-co-glycolic acid) (PLGA) controlled release microspheres has become more attractive for this class of drugs upon the discovery that net positively charged peptides can be remote-loaded rapidly from aqueous peptide solution into blank microspheres at high loading and encapsulation efficiency. Here we sought to remote-load setmelanotide in PLGA microspheres and examine its potential for long-term controlled release and body weight control. The influence of PLGA microsphere porosity was investigated with respect to morphology, drug loading, and in vitro release profiles. Increased density of the microspheres inhibited the progress of encapsulation of the dicationic peptide. A diet-induced obese murine model was then used to determine the pharmacokinetic profile and to evaluate long-term efficacy of an optimal formulation. Remote loaded PLGA formulations encapsulated setmelanotide as high as ∼63% (∼6.3% w/w loading) and exhibited slow and continuous peptide release over ∼6 weeks in vitro largely independent of microsphere porosity. The obtained in vivo release pattern from deconvolution of the pharmacokinetics after subcutaneous microsphere injection was consistent with the in vitro release profile but with a lower initial burst release and overall slightly faster release rate. After a single injection of remote-loaded setmelanotide, continuous long-term inhibition of food intake and body weight control was observed over 17 and 30 days, respectively. The improvement in body weight control over drug-free microsphere vehicle-treated control groups matched the observed PK profile. This study provides the first report of long-acting release formulation for 1-month controlled release of setmelanotide and body weight control in a diet induced obese murine model, and supports the further development of long-acting treatment options for obese patients.

Modern approaches to drug treatment of obesity

The issue of obesity is relevant for countries all over the world. The article discusses available, currently recommended, and anticipated medications for chronic weight control. Pharmacological approaches are appropriate to use in order to maximize the effectiveness of non-pharmacological interventions in the long-term treatment of obesity. As an adjunct to lifestyle modification, pharmacological interventions may promote clinical weight loss.

The impact of bariatric surgery on liver enzymes in people with obesity: A 5-year observational study

Background and purposeNon-alcoholic fatty liver disease (NAFLD) has increasing worldwide prevalence, fuelled by rising obesity rates, and weight reduction is the mainstay of its management. We sought to study the effect of bariatric surgery, the most effective long-term treatment for obesity and associated metabolic disorders, on liver function in people with obesity. MethodsWe performed a retrospective longitudinal cohort study of 511 patients who had undergone bariatric surgery (71 sleeve gastrectomy and 440 gastric bypass) over 60 months of follow-up. Patients were stratified into groups based on their baseline alanine aminotransferase (ALT) into Group A (ALT < 40 U/L) and Group B (ALT > 40 U/L). Postoperative follow-up weight loss, liver function tests, HbA1c, blood pressure and lipid profiles were collected. FindingsBariatric surgery resulted in nadir total weight loss of 33.1% by 24 months (p < 0.001) with no significant difference between groups. In people with raised baseline ALT (Group B), ALT and gamma glutamyl transferase (GGT) levels decreased significantly by 4 months postoperatively (p < 0.001) and sustained over 60 months of follow-up. There was also significant and sustained reduction in HbA1c, blood pressure, total cholesterol, and non-HDL cholesterol overall with no differences between groups. ConclusionsBariatric surgery results in significant weight loss, improves liver function tests and metabolic outcomes in people with obesity. Bariatric surgery could be a therapeutic consideration for patients with NAFLD associated with severe obesity who have otherwise been unresponsive to conservative management.

Perioperative optimization and profitability (POP) in a high-volume bariatric surgery center.

Currently, bariatric surgery is the most effective long-term treatment of obesity. Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) are the primary types of bariatric surgery performed worldwide. To minimize the risks of surgical complications and optimize cost-effectiveness, it is essential to develop fast-track protocols and patient logistics. At Aleris Hospitals in Denmark, a fast-track methodology in bariatric surgery has been implemented and continuously optimized over the last 15years. The main objective was to demonstrate timelines recorded during one consecutive year in a fast-track, high-volume bariatric surgery setting after logistic optimization. This study included 949 consecutive patients who had undergone primary bariatric surgery in 2021. The primary outcomes were length of hospital stay and perioperative timeline recordings that were prospectively collected. The secondary outcomes were mortality, complication rates, and weight loss data. The vast majority of our patients (99.1%) were discharged from the hospital within the day after surgery. The median total surgery time was 30min, after 12min of patient preparation and with a turnover time between patients of seven min. The median knife-to-knife time in one operating room was 56min. Mortality was zero, 30-day reoperation rate was 1.2%, and 30-day readmission rate was 0.8%. SG and RYGB patients had an excess weight loss after four months of 45.6% and 57.9%, respectively. Implementation of fast-track principles in the clinical practice of bariatric surgery allows for an optimized, cost-effective surgical organization supporting the quality of procedures and patient safety.

V-care: An application to support lifestyle improvement in children with obesity

BackgroundObesity is increasing in the pediatric population, and it represents an important risk factor for the life-long development of several diseases. Although health promotion represents the mainstay of obesity prevention and treatment, lifestyle modification programs are often unsuccessful. ObjectivesThe purpose of this article is to introduce the V-care app, a mobile health platform specifically developed to offer effective interaction and support young people in a long-term obesity treatment, combining different strategies to maximize the results of the lifestyle modification program and minimize the possibility of dropouts. MethodsThe V-care app is based on a conventional client–server architecture, but novelties of our approach are the involvement of families in the lifestyle modification program, and the design inspired to psychological/behavioral change theories, with the aim of raising the chance of patients’ compliance to the program. V-care implements a goal-based behavioral intervention, providing specific feedbacks according to the patient's performance. A pilot usability and acceptability study was performed on a sample of thirteen children aged 6–12 years, using a questionnaire with a 5-points Likert scale to evaluate eight system features, identified as essential requirements based on the analysis of strengths and weaknesses of similar systems in literature. ResultsThe pilot study highlighted very high rate of overall friendliness and perceived utility evaluation, while some critical issues emerged especially for the chatbot section, which may be due to the novelty of the technology. The positive evaluation of the design choices is confirmed by the average score greater than 3 for all the questions. ConclusionsThe V-care app represents a digital innovation in the pediatric healthcare, and it could be introduced in children's primary healthcare nationwide, with the aim to offer an intervention program for controlling and preventing childhood obesity.

In vitro study of effective factors for the inhibitory assay on pancreatic lipase

Background: Pancreatic lipase is one of the safest targets of anti-obesity drugs. To date, orlistat is the only pancreatic lipase inhibitor approved for the long-term treatment of obesity. Therefore, there is an elevated need to find new drugs for this disease. Determining the factors affecting the test to evaluate pancreatic lipase inhibitory activity in order to build a standard assay procedure is necessary. This will make it much easier for researchers to find novel compounds that inhibit the enzyme. Materials and method: The current study investigated the factors influencing pancreatic lipase activity and evaluated the enzyme inhibition of orlistat by spectrophotometric method at 405 nm using p-nitrophenyl palmitate as a substrate. Results: With the optimized conditions, the test to evaluate pancreatic lipase inhibitory activity of orlistat gave results similar to those published by other authors. Conclusion: The methodology of this work should be applied in the studies looking for new effective drugs to treat obesity. Key words: obesity, orlistat.

Current pharmacological approaches in obesity treatment

Obesity is a complex disorder and affected by so many factors in which the balance between food consumption and calorie usage is disrupted. Drugs that act on appetite, food intake, calorie absorption or calorie consumption, or a combination of these, are basically central or peripheral agents. Diethylpropion and phentermine are preferred for short-term obesity treatment. Orlistat, lorcaserin, topiramate/phentermine, naltrexone/bupropion, and liraglutide are preferred for long-term obesity treatment. The main drugs whose experimental and clinical phase studies are still ongoing are setmelanotide, zonisamide/bupropion, neuropeptide Y antagonists, semaglutide and oral glucagon-like peptide-1 agonists, cannabinoid type-1 receptor inhibitors, amylin mimetics, amylin/calcitonin receptor activators, glucose-linked insulin-like acting peptide analogues, dual-acting glucagon-like peptide-1/glucagon receptor agonists, peptide YY, leptin analogues, beloranib, cetilistat, tenofensin, fibroblast growth factor-21 and obesity vaccines. While managing the treatment of an obese patient, considering the large costs of the disease and the high incidence of disorder, pharmacotherapeutic agents are not enough to meet the clinic spectrum like adverse effects and contraindications, but new drugs and studies in this field offer hope to the medical world in terms of efficacy and safety profile. However, it would not be rational to expect miracles from drugs without a change in lifestyle in the magement of this disorder.

BP Limb Length as a Factor for T2DM Remission

Background: There has been increased interest in identifying the associated factors to Type 2 Diabetes Mellitus (T2DM) remission after bariatric surgery. One of these factors is the BP limb length. The objective of our study was to evaluate the T2DM remission rate in patients subjected to Roux -en- Y gastric bypass (RYGB) who had different Biliopancreatic (BP) limbs length. Methods: 48 patients with obesity grade II, and T2DM diagnosis, were subjected to RYGB and completed a one year of surgical follow up. All patients were grouped according to the BP limb length: In group A (n= 24) patients with BP limbs of 100 cm or less; in group B (n= 24) patients with BP limb from 150 to 170 cm in length. Results: Both groups presented an elevated remission rate of T2DM (83% full remission in the population studied). In group A 18 patients (75%) presented a full remission, while 2 patients (8.3%) showed a partial remission and only 4 patients (16.7%) were considered without remission at the one year follow up. In group B all patients had some remission: 22 patients (91.7%) presented a full remission (91.7%) and the rest of the patients showed a partial remission (8.3%), no significant difference was found between the two groups. Conclusions: Bariatric surgery remains as the best long term treatment for obesity and its comorbidities, despite some differences in the RYGB technique, BP limb length from 50 to 170 cm did not affect post RYGB glycemic control.

Five-year Weight Loss Maintenance With Obesity Pharmacotherapy.

Long-term treatment of obesity with lifestyle changes alone is unsustainable for most individuals because of several factors including adherence and metabolic adaptation. Medical management of obesity has proven efficacy for up to 3 years in randomized controlled trials. However, there is a dearth of information regarding real-world outcomes beyond 3 years. This work aimed to assess long-term weight loss outcomes over a 2.5- to 5.5-year period with US Food and Drug Administration (FDA)-approved and off-label antiobesity medications (AOMs). A cohort of 428 patients with overweight or obesity were treated with AOMs at an academic weight management center with an initial visit between April 1, 2014, and April 1, 2016. Intervention included FDA-approved and off-label AOMs. The primary outcome was percentage weight loss from initial to final visit. Key secondary outcomes included weight reduction targets as well as demographic and clinical predictors of long-term weight loss. The average weight loss was 10.4% at a mean follow-up duration of 4.4 years. The proportions of patients who met the weight reduction targets of 5% or greater, 10% or greater, 15% or greater, and 20% or greater were 70.8%, 48.1%, 29.9%, and 17.1%, respectively. On average, 51% of maximum weight loss was regained, while 40.2% of patients maintained their weight loss. In a multivariable regression analysis, a higher number of clinic visits was associated with more weight loss. Metformin, topiramate, and bupropion were associated with increased odds of maintaining 10% or greater weight loss. Clinically significant long-term weight loss of 10% or more beyond 4 years is achievable in clinical practice settings with obesity pharmacotherapy.

Bariatric Surgery as Treatment Strategy of Obesity in Saudi People: Effects of Gut Microbiota

Obesity prevalence is rising globally, as are the number of chronic disorders connected with obesity, such as diabetes, non-alcoholic fatty liver disease, dyslipidemia, and hypertension. Bariatric surgery is also becoming more common, and it remains the most effective and long-term treatment for obesity. This study will assess the influence of Laparoscopic Sleeve Gastrectomy (LSG) on gut microbiota in people with obesity before and after surgery. The findings shed new light on the changes in gut microbiota in Saudi people with obesity following LSG. In conclusion, LSG may improve the metabolic profile, resulting in decreased fat mass and increased lean mass, as well as improving the microbial composition balance in the gastrointestinal tract, but this is still not equivalent to normal weight microbiology. A range of factors, including patient characteristics, geographic dispersion, type of operation, technique, and nutritional and caloric restriction, could explain differences in abundance between studies. This information could point to a novel and, most likely, tailored strategy in obesity therapy, which could eventually be incorporated into health evaluations and monitoring in preventive health care or clinical medicine.

Contents, Actions and Efficacy of Weight Reduction Medications Available in the Drugs Markets, Benghazi, Libya

Background: Obesity pharmacotherapy has evolved significantly over the past 60 years. Today, six anti-obesity medications (AOMs) are approved by the Federal Drug Administration (FDA) for the long-term treatment of obesity. The aim of the present work was to investigate the types of weight management medication dispensed to patients seeking of weight reduction products in the drug markets, also know their contents, purpose and action. Methods: This cross sectional study conducted in pharmacies and OPD patients with overweight and obesity. Predesigned questionnaire was validity for patients and pharmacies. The total samples collected 150 (53 males and 97 female). The data was analysis by Chi-square test and T test at α&lt; 0.05. Result: The result of this study revealed that, weight managements medication used by the patients most of them not approved by FDA and contain different ingredients such as antioxidants, antidepressant, dietary fibre, anti-aging, laxative and some of the ingredient have unknown function. While other regulate blood pressure, heart function, sleeping and glucose metabolism. On the other hands the other ingredients have been found associated with appetite suppression or weight loss. The most common weight management product available in the drug markets for weight reduction were found fit slim, green tea, green coffee and orlistat, 20%, 18%, 14.7% and 8% respectively. There were some improved in health status after using the weight management products include anaemia, depression. However, there was evidence for developing of ulcer and GIT disorder after using some of weight management products. The common effect of weight management products for body weight, BMI and waist size reduction was green coffee (P&lt; 0.05), while the other products mostly significant effect on reduction of weight and/ or BMI or waist (P&lt; 0.05). Conclusion: The present study revealed that, different number of products were dispensing which were not approved by FDA which contain ingredient may increasing GIT disturbance. The most weight management medication has approved it efficacy in weight reduction was green coffee. Even though, achievement of body weight reduction with some products but these still needed to be supervised and further investigation.

Semaglutide 2.4-mg injection as a novel approach for chronic weight management.

Anti-obesity medications used with lifestyle intervention produce greater and more sustained weight loss than does lifestyle intervention alone. However, until 2021, FDA-approved medications for the long-term treatment of obesity in the general adult population had not demonstrated the sustained loss of 15% body weight needed to meet or exceed all guideline-recommended targets for weight-related complications. To meet this need, investigators launched the Semaglutide Treatment Effect in People with obesity (STEP) program of phase 3 clinical trials to assess the safety and efficacy of a weekly 2.4-mg subcutaneous injection of semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA). Following the results of STEPs 1 to 4, the FDA approved semaglutide therapy in patients with obesity. This article examines the design, efficacy, and safety of semaglutide therapy as revealed by the results of STEPs 1 to 4. These trials included adults with obesity who reported at least 1 unsuccessful attempt to reduce body weight by means of diet. STEP 2 studied effects on patients who also had type 2 diabetes (T2D); STEPs 1, 3, and 4 excluded patients with this condition. STEP 3 examined the effect of this pharmacotherapy plus intensive behavioral therapy and a 2-step, intensively restricted dietary plan. STEP 4 assessed the effects of continuing semaglutide 2.4 mg vs switching to placebo after an initial treatment period. In the trials comparing the effects of semaglutide 2.4‑mg treatment with those of placebo across 68 weeks and in patients with no T2D (ie, STEPs 1 and 3), patients treated with semaglutide achieved a mean -14.9% to -16.0% weight change. This far exceeds the 4.0% to 10.9% weight loss seen with other approved antiobesity medications. In STEPs 2 and 4, the estimated treatment differences between the semaglutide 2.4-mg and placebo arms were -6.2% and -14.8%, respectively. Safety and tolerability of this treatment in STEPs 1 to 4 was consistent with those of other GLP-1RA-based therapies. Ultimately, the results of the first 4 STEP trials demonstrated that semaglutide 2.4 mg is a safe, well-tolerated, and highly effective treatment to promote weight loss, avoid weight regain, and mitigate the effects of the prevalent, chronic disease of obesity. In November 2022, based upon the results of STEPs 1 to 3 and other trials, the American Gastroenterological Association recommended that semaglutide 2.4 mg "be prioritized over other approved [anti-obesity medications] for the long-term treatment of obesity for most patients."

Molecular modelling, synthesis and in vitro evaluation of quinazolinone hybrid analogues as potential pancreatic lipase inhibitors

Obesity is a multifactorial metabolic disorder, growing in an alarming rate across the world. Amongst the numerous targets explored for obesity management, inhibition of pancreatic lipase (PL) is considered as one of the promising approaches. Orlistat is the only PL inhibitory drug approved for long term treatment of obesity. However, it is reported to possess hepatotoxicity and nephrotoxicity. Thus, novel drug candidates that act through PL inhibition are considered the hour’s need. Based on this aim, a series of quinazolinone hybrid analogues have been synthesized, characterized and evaluated for their PL inhibitory potential. The physicochemical properties and toxicity parameters suggested that these parameters are in an acceptable range for the screened analogues. Amongst the synthesised analogues, QH-25 exerted potential PL inhibition (IC50 = 16.99 ± 0.54 µM). Further, enzyme inhibition studies suggested a reversible competitive inhibition. Molecular docking of these analogues was in line with in vitro results, wherein the obtained MolDock scores exhibited a significant correlation with their inhibitory activity (Pearson’s r = 0.6629). To further confirm the stability of the QH-25-PL complex in a dynamic environment, a molecular dynamics study (100 ns) was carried out and the results suggested that this complex is stable at dynamic conditions. Overall, these results shed light on the quinazolinone hybrids as potential PL inhibitors. Further structural modification may result in the development of potent anti-obesity agents which acts through PL inhibition. Communicated by Ramaswamy H. Sarma

Feasibility Study of Bariatric Surgery in a Rat Model of Spinal Cord Injury to Achieve Beneficial Body Weight Outcome.

Approximately two thirds of spinal cord injury (SCI) persons become overweight or obese. Obesity increases the risk of developing type 2 diabetes and limits self-help techniques. Weight-loss surgery (WLS), including vertical sleeve gastrectomy (VSG), is regarded as highly effective in the long-term treatment of obesity and remission of associated type 2 diabetes. Given the increased risk of obesity post-SCI, WLS offers an attractive intervention strategy. Alterations in the physiology of energy homeostasis after SCI necessitate that SCI persons should not be regarded as similar to able-bodied persons. Because of current knowledge gaps, it is unknown whether an obese phenotype with SCI will respond to WLS similarly to the neurally intact obese phenotype. Therefore, this study tested the hypothesis that the VSG procedure is well tolerated and effective in an animal model of high-thoracic (T3) SCI. In Wistar male rats, subsequent to a 2-week recovery period after T3-SCI, but not control laminectomy surgery, daily consumption of a high-fat diet (HFD; 60% kcal from fat) was elevated over 4 weeks preceding VSG. After a 2-week recovery period post-VSG, HFD consumption in T3-SCI rats over a 4-week monitoring period returned to levels comparable to control. Body weight was significantly reduced in T3-SCI rats and remained reduced whereas control rats regained body weight. Further, no adverse complications directly attributable to the VSG procedure were identified. Thus, this rodent model is a viable tool for addressing fundamental questions regarding the mechanisms leading to obesity post-SCI and the development of translational strategies.

Weight-Loss Strategies for Prevention and Treatment of Hypertension: A Scientific Statement From the American Heart Association.

Hypertension is a major risk factor for cardiovascular and renal diseases in the United States and worldwide. Obesity accounts for much of the risk for primary hypertension through several mechanisms, including neurohormonal activation, inflammation, and kidney dysfunction. As the prevalence of obesity continues to increase, hypertension and associated cardiorenal diseases will also increase unless more effective strategies to prevent and treat obesity are developed. Lifestyle modification, including diet, reduced sedentariness, and increased physical activity, is usually recommended for patients with obesity; however, the long-term success of these strategies for reducing adiposity, maintaining weight loss, and reducing blood pressure has been limited. Effective pharmacotherapeutic and procedural strategies, including metabolic surgeries, are additional options to treat obesity and prevent or attenuate obesity hypertension, target organ damage, and subsequent disease. Medications can be useful for short- and long-term obesity treatment; however, prescription of these drugs is limited. Metabolic surgery is effective for producing sustained weight loss and for treating hypertension and metabolic disorders in many patients with severe obesity. Unanswered questions remain related to the mechanisms of obesity-related diseases, long-term efficacy of different treatment and prevention strategies, and timing of these interventions to prevent obesity and hypertension-mediated target organ damage. Further investigation, including randomized controlled trials, is essential to addressing these questions, and emphasis should be placed on the prevention of obesity to reduce the burden of hypertensive cardiovascular and kidney diseases and subsequent mortality.

The Panoramic View of Revisional Bariatric Surgery.

Introduction: Obesity remains a major public chronic disease, and the multifactorial components of its relapse in many patients remain inevitable. Methods: This article provides a panoramic view of the most commonly performed revisional bariatric surgery (RBS). RBS is a complex procedure; thus, primary procedures should be well chosen and performed to avoid the increasing number of RBS cases. Results: Bariatric surgery is the only successful long-term treatment for obesity. However, a proportion of primary bariatric surgeries has failed during the follow-up period. In recent decades, the solution for these complications is by performing RBS. It is mandatory to understand obesity as a chronic disease to appropriately treat patients. Treatment strategies are needed to determine the indications for revision. RBS requires a meticulous evaluation to facilitate good long-term results. Conclusions: Treatment strategies will be a fundamental pillar to wisely determine the indications for revision and identify the factors influencing failure by prudently and rationally evaluating the revisional procedure that the patient will benefit from and acquiring a high level of surgical skills.

Synthesis, molecular modelling, in vitro and in vivo evaluation of conophylline inspired novel benzyloxy substituted indole glyoxylamides as potent pancreatic lipase inhibitors

Pancreatic lipase is a digestive enzyme involved in the hydrolysis of dietary fats. Orlistat, a potent pancreatic lipase inhibitor, is widely prescribed for long-term obesity treatment. Nevertheless, orlistat is reported for severe adverse effects including hepatotoxicity and pancreatitis. In the present study, a novel series of 11 benzyloxy substituted indole glyoxylamides were designed, synthesized and evaluated for in vitro pancreatic lipase inhibitory activity. Three analogues, 10b, 11b and 11c, exhibited potent activity (IC50 ≤ 2.5 µM), with 11b exhibiting a potent IC50 of 1.68 µM comparable to orlistat (IC50 = 0.99 µM). Further, 11b exhibited reversible competitive inhibition with an inhibitory constant value of 0.98 μM. Molecular docking of these analogues was in agreement with in vitro results, wherein the MolDock scores exhibited significant correlation with their inhibitory activity (Pearson’s r = 0.7122). A 50 ns molecular dynamics simulation of 11b-pancreatic lipase complex confirmed the role of extended alkyl interactions along with π-π stacking and π-cation interactions, in stabilizing the ligand (Maximum RMSD ≈ 3 Å) in the active site. Gastro-intestinal absorption and toxicity prediction of the three potent analogues highlighted the suitability of 11b for in vivo experiments. 11b at a dose of 20 mg/kg exhibited anti-obesity efficacy comparable to orlistat (10 mg/kg), wherein the serum triglycerides were found to be 94.95 and 83.85 mg/dL, respectively. Further, faecal triglyceride quantification indicated 11b to act through pancreatic lipase inhibition similar to orlistat. The present study identified a novel pancreatic lipase inhibitory benzyloxy substituted bis(indolyl) glyoxylamide 11b, with promising anti-obesity activity. Communicated by Ramaswamy H. Sarma

Alpha-lipoic acid supplementation increases the efficacy of exercise- and diet-induced obesity treatment and induces immunometabolic changes in female mice and women.

The decrease in the regulatory T cells (Tregs) population is highly involved in adipose tissue inflammation and insulin resistance in obesity. Tregs depend on fatty acids via β-oxidation for immunosuppressive function adapting their antioxidant systems to allow survival to oxidative stress. In this study, we have hypothesized that a dietary supplementation with alpha-lipoic acid (ALA), a powerful antioxidant, would improve immunometabolism when added to the classical strategy of obesity treatment. First, we showed by in vitro experiments that ALA favors the polarization of mice CD4+T cells toward Tregs. Next, we have carried out a translational study where female obese mice and women were supplemented with ALA or vehicle/placebo (mice: 2.5 gALA /kgfood ; 6weeks; women: 600 mgALA /day, 8weeks) while following a protocol including regular exercise and a change in diet. Fatty acid oxidation potential and activity of nuclear erythroid-related factor 2 (NRF2) of mouse secondary lymphoid tissues were improved by ALA supplementation. ALA reduced visceral adipose tissue (VAT) mass and preserved Tregs in VAT in mice. In women, ALA supplementation induced significant metabolic changes of circulating CD4+T cells including increased oxidative capacity and fatty acid oxidation, ameliorated their redox status, and improved the reduction of visceral fat mass. While appropriate biological markers are still required to be used in clinics to judge the effectiveness of long-term obesity treatment, further studies in female mice and women are needed to determine whether these immunometabolic changes would reduce VAT mass-associated risk for secondary health issues arising from obesity.