Addressing disparities: A systematic review of digital health equity for adolescent obesity prevention and management interventions.

Adolescence is a high-risk life stage for obesity. Digital strategies are needed to prevent and manage obesity among adolescents. We assessed if digital health interventions are contributing to disparities in obesity outcomes and assessed the adequacy of reporting of digital health equity criteria across four levels of influence within the digital environment. The systematic search was conducted on 10 major electronic databases and limited to randomized controlled trials (RCTs) or cluster-RCTs for prevention or management of obesity among 10-19 year olds. Primary outcome was mean body mass index (BMI), or BMI z-score change. The Adapted Digital Health Equity Assessment Framework was applied to all studies. Thirty-three articles (27 unique studies with 8483 participants) were identified, with only eight studies targeting adolescents from disadvantaged populations. Post-intervention, only three studies reported significantly lower BMI outcomes in the intervention compared to control. Of the 432 digital health equity criteria assessed across 27 studies, 82% of criteria were "not addressed." Studies are not addressing digital health equity criteria or inadequately reporting information to assess if digital health interventions are contributing to disparities in obesity outcomes. Enhanced reporting is needed to inform decision-makers and support the development of equitable interventions to prevent and manage obesity among adolescents.

Anti-Obesity Medication in the Management of Children and Adolescents With Obesity: Recent Developments and Research Gaps.

BACKGROUND: Paediatric obesity is a global public health concern. While in most countries the incidence keeps rising, the need for effective and long-term management for children and adolescents living with this chronic, relapsing disease is pressing. Health behaviour and lifestyle treatment (HBLT) is recommended as first-line treatment. METHODS: Narrative review. RESULTS: A new generation of recently approved anti-obesity medications (AOM) now has the potential to fill the gap between limited effects on body mass index (BMI) by HBLT alone and large effects by metabolic and bariatric surgery in adolescents with obesity aged 12 years and older. While, for semaglutide and phentermine/topiramate, effectiveness is substantial with relevant, but mostly mild to moderate adverse events, there is a gap in evidence regarding long-term effects and safety, effects on outcomes beyond BMI reduction and data for certain groups of patients, such as children < 12 years and minority groups. When integrating AOM treatment into national healthcare systems it should be offered as part of a comprehensive patient-centred approach. CONCLUSION: This article summarizes recent AOM developments, integration into paediatric obesity management, and identifies research gaps.

Maternal obesity management: a narrative literature review of health policies.

Maternal obesity rates are increasing significantly, posing substantial risks to both mothers and their children. This study aims to introduce health policies addressing maternal obesity, identify preventive interventions, and highlight scientific gaps necessitating further research.We identified documents through electronic searches in PubMed, CINAHL Plus, EMBASE, and grey literature sources (ministry of health websites, national gynecology and obstetrics associations) from January 2013 to August 2023, updated in June 2024. The inclusion criteria focused on English-language documents discussing interventions or health policies that promote weight loss through lifestyle changes during pregnancy.A total of 22 documents (10 studies and 12 guidelines) were included. 12 studies (N=1244) identified via databases; included two Clinical Practice Guidelines (CPGs) from Canada and Singapore. Other 10 CPGs sourced from governmental websites and national associations: England (1), Australia (1), New Zealand (1), combined Australia and New Zealand (1), Canada (3), USA (1), Ireland (1), Germany (1). 10 guidelines focused on obesity in pregnancy, two on weight management during pregnancy. Covered interventions across pre-pregnancy, pregnancy, and postpartum periods (9 guidelines); pre-pregnancy and pregnancy (2); exclusively postpartum (1). Seven guidelines offered evidence-based recommendations on maintaining healthy weight in mothers, largely based on expert opinions.Maternal obesity poses significant risks to both mothers and children, underscoring the need for effective health policies and systems. However, few countries have integrated adequate responses into their healthcare policies and guidelines for professionals. Limited evidence exists on optimal practices to improve reproductive health outcomes in obese women. Hence, the crucial need to developing comprehensive guidelines and proactive strategies to manage maternal obesity. These measures can improve outcomes and reduce healthcare costs. Increased focus on research and policymaking is essential to protect the health of mothers and their children.

Peptides Evaluated In Silico, In Vitro, and In Vivo as Therapeutic Tools for Obesity: A Systematic Review.

Bioinformatics has emerged as a valuable tool for screening drugs and understanding their effects. This systematic review aimed to evaluate whether in silico studies using anti-obesity peptides targeting therapeutic pathways for obesity, when subsequently evaluated in vitro and in vivo, demonstrated effects consistent with those predicted in the computational analysis. The review was framed by the question: "What peptides or proteins have been used to treat obesity in in silico studies?" and structured according to the acronym PECo. The systematic review protocol was developed and registered in PROSPERO (CRD42022355540) in accordance with the PRISMA-P, and all stages of the review adhered to these guidelines. Studies were sourced from the following databases: PubMed, ScienceDirect, Scopus, Web of Science, Virtual Heath Library, and EMBASE. The search strategies resulted in 1015 articles, of which, based on the exclusion and inclusion criteria, 7 were included in this systematic review. The anti-obesity peptides identified originated from various sources including bovine alpha-lactalbumin from cocoa seed (Theobroma cacao L.), chia seed (Salvia hispanica L.), rice bran (Oryza sativa), sesame (Sesamum indicum L.), sea buckthorn seed flour (Hippophae rhamnoides), and adzuki beans (Vigna angularis). All articles underwent in vitro and in vivo reassessment and used molecular docking methodology in their in silico studies. Among the studies included in the review, 46.15% were classified as having an "uncertain risk of bias" in six of the thirteen criteria evaluated. The primary target investigated was pancreatic lipase (n = 5), with all peptides targeting this enzyme demonstrating inhibition, a finding supported both in vitro and in vivo. Additionally, other peptides were identified as PPARγ and PPARα agonists (n = 2). Notably, all peptides exhibited different mechanisms of action in lipid metabolism and adipogenesis. The findings of this systematic review underscore the effectiveness of computational simulation as a screening tool, providing crucial insights and guiding in vitro and in vivo investigations for the discovery of novel anti-obesity peptides.

Nurses' Role in Obesity Management in Adults in Primary Healthcare Settings Worldwide: A Scoping Review.

Obesity is a chronic, prevalent, and complex health condition that adversely impairs physical and mental health. The World Health Organization calls for integrating obesity care into existing chronic disease management programs within primary healthcare services. This scoping review aimed to examine registered nurses' roles in the primary healthcare management of individuals with obesity. A scoping review was conducted using the Johanna Briggs Institute methodology framework. Thematic analysis was used to identify and categorize nurses' roles in primary healthcare obesity management of adults. Of 1142 documents included in this review, 15 papers met the inclusion criteria. Thematic analysis yielded the following six themes representing nurses' major roles: patient-centred care, patient assessments, therapeutic interventions, care management, patient education, and professional development. This review identified that the literature on nurses' roles primarily described their focus on lifestyle interventions (mainly nutrition and physical activity), anthropometric measurements, health planning, goal setting, supportive care, monitoring progress, and arranging follow-up. The Discussion highlights the importance of determining RN knowledge gaps and biases. More research is required to determine the need for additional RN pre-and or post-education related to obesity as a complex chronic disease.

Development of the International Federation for Surgery of Obesity and Metabolic Disorders-European Chapter (IFSO-EC) Grade-Based Guidelines on the Surgical Treatment of Obesity Using Multimodal Strategies: Design and Methodological Aspects.

Background: The prevalence of obesity is already a worldwide health concern. The development of straightforward guidelines regarding the whole available armamentarium (i.e., medical, endoscopic, and surgical interventions in conjunction with a guidance program) is paramount to offering the best multimodal approach to patients with obesity. Methods: The International Federation for Surgery of Obesity and Metabolic Disorders-European Chapter (IFSO-EC) identified a panel of experts to develop the present guidelines. The panel formulated a series of clinical questions (based on the patient, intervention, comparison, and outcome conceptual framework), which have been voted on and approved. A GRADE methodology will be applied to assess the quality of evidence and formulate recommendations employed to minimize selection and information biases. This approach aims to enhance the reliability and validity of recommendations, promoting greater adherence to the best available evidence. Results: These guidelines are intended for adult patients with a body mass index (BMI) ≥ 30 kg/m2 who are candidates for metabolic bariatric surgery (MBS). The expert panel responsible for developing these guidelines comprised 25 panelists (92% were bariatric surgeons) and 3 evidence reviewers, with an average age of 50.1 ± 10.2 years. The panel focused on 3 key questions regarding the combined use of structured lifestyle interventions, approved obesity management medications, and endoscopic weight loss procedures with MBS. Conclusions: The complexity of obesity as a chronic disease requires a comprehensive knowledge of all the available and feasible therapeutic options. The IFSO-EC society felt the urgent need to develop methodologically valid guidelines to give a full picture and awareness of the possible surgical and non-surgical therapeutic strategies employed with a multimodal approach.

How do gamified digital therapeutics work on obesity self-management?

Obesity management can effectively reduce the risks and complications associated with obesity and improve the quality of life of patients. After assessing the advantages and limitations of various obesity management approaches, self-management has been strongly recommended due to the advantages of minimal side effects and lower costs compared to treatment via drugs and surgery. However, successfully implementing lifestyle intervention strategies requires scientific guidance and strong determination. With the development of electronic and information technology, lifestyle intervention has transformed considerably. A new concept, called Gamified Digital Therapeutics (GDTx), represents a gaming format with Digital Therapeutics (DTx). It can effectively enhance patient compliance and accessibility to chronic disease management. Here, we review recent studies on the application of GDTx for the self-management of obesity and discuss three aspects surrounding its completion rates, satisfaction levels, and effectiveness. In contrast to traditional approaches to obesity self-management, implementing GDTx effectively corrects unhealthy dietary and lifestyle habits, markedly enhancing the dissemination of nutritional and exercise-related health knowledge. Of particular significance is the evident improvement in the adherence of obese patients to weight loss programs. Despite numerous studies indicating that GDTx may offer an effective solution for obesity self-management, there are still several limitations in the medicalization of GDTx for self-management of obesity. This review aimed to provide a reference for subsequent studies and promote the widespread application of GDTx in obesity self-management to help reduce the obesity rate and alleviate the burden on obese patients.

Adoption of telemedicine for obesity treatment during the COVID-19 pandemic achieved comparable outcomes to in-person visits.

Background: During the COVID-19 pandemic, weight loss programs rapidly transitioned to a virtual model, replacing in-person clinic visits. We sought to compare the observed weight loss and adherence to treatment between patients referred for intensive behavioral therapy (IBT) who were treated via telemedicine and those treated in person. Methods: After IRB approval, we conducted a retrospective observational study of patients referred for clinical bariatric IBT between January 2019 and June 2021 who were followed in person or via telemedicine. The primary endpoint was the percentage of excess BMI loss (EBL%); secondary endpoints included treatment adherence, duration of follow-up, and number of completed visits. Results: During the study period, 139 patients were seen for at least one IBT session for weight management: 62 were followed up in person (IP) and 77 via telemedicine (TM). The mean age, baseline BMI, and follow-up duration between the groups were similar. In the IP and TM groups, the EBL% was -24.7 ± 24.7 and -22.7 ± 19.5 (P = 0.989) and loss to follow-up after the first visit was 27.4% and 19.5% (P = 0.269), respectively. Conclusion: For the management of obesity, weight loss programs delivered via telemedicine can achieve similar outcomes to those provided via classical in-person visits. This study suggests that the integration of telecare into clinical practice in bariatric medicine should be considered in the future. Emerging technologies may allow adequate patient follow-up in multiple scenarios, specifically non-critical chronic disorders, and bring unanticipated benefits for patients and healthcare providers.

Long-term safety and efficacy of glucagon-like peptide-1 receptor agonists in individuals with obesity and without type 2 diabetes: A global retrospective cohort study.

AIM: We aimed to investigate the long-term impact of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on thyroid function, cardiovascular health, renal outcomes and adverse events in individuals with obesity and without type 2 diabetes (T2D). MATERIALS AND METHODS: In this observational cohort study, we used propensity score matching to construct comparable cohorts of individuals with obesity and without T2D who were new to GLP-1 RA treatment and those who did not receive glucose-lowering medications. In total, 3,729,925 individuals with obesity were selected from the TriNetX Global Network, with an index event between 1 January 2016 and 31 March 2024. The primary outcomes were safety, cardiovascular, thyroid and clinical biochemical profile outcomes occurring within 5 years following the index event. RESULTS: After propensity score matching, the study included 12,123 individuals in each group. GLP-1 RA treatment was associated with a significantly lower risk of all-cause mortality (hazard ratio 0.23; 95% confidence interval 0.15-0.34) and several cardiovascular complications, including ischaemic heart disease, heart failure, arrhythmias, hypertension, stroke and atrial fibrillation (all p < 0.05). GLP-1 RAs were also associated with a lower risk of acute kidney injury and allergic reactions. These protective effects were consistent across various subgroups and regions. CONCLUSIONS: In this large observational study, GLP-1 RAs showed long-term protective effects on cardiovascular health, renal outcomes and adverse events in individuals with obesity and without T2D. Our findings suggest that GLP-1 RAs may offer a comprehensive approach to managing obesity and its related comorbidities, potentially improving overall health and survival in this population.

Effect of positive airway pressure on obese patients undergoing surgery: a systematic review and meta-analysis.

This systematic review and meta-analysis (SRMA) evaluates the efficacy and safety of Positive Airway Pressure (PAP) therapy in perioperative care for obese surgical patients. We reviewed 24 studies, encompassing data up to March 23, 2023, analyzing the impacts of Continuous Positive Airway Pressure (CPAP) and Bilevel Positive Airway Pressure (BIPAP) on postoperative adverse outcomes, oxygenation, and pulmonary function. Our findings underscore the significant potential of PAP therapy in managing obese patients during the perioperative period, particularly those at substantial risk for postoperative respiratory complications. PAP therapy not only enhances oxygenation levels and lung function but also substantially reduces the incidence of atelectasis and shortens hospital stays, thereby affirming its vital role in improving perioperative outcomes for this patient population.

Diagnostic and therapeutic challenges for PCPs regarding heart failure with preserved ejection fraction and obesity: results of an online internet-based survey.

BACKGROUND: Obesity (body mass index ≥ 30 kg/m2) is a major risk factor for heart failure with preserved ejection fraction (HFpEF) and affects most patients with HFpEF. Patients living with obesity may experience delays in HFpEF diagnosis and management. We aimed to understand the clinical journey of patients with obesity and HFpEF and the role of primary care providers (PCPs) in diagnosing and managing patients with both conditions. METHODS: An anonymous, US population-based online survey was conducted in September 2020 among 114 patients with self-reported HFpEF and obesity and 200 healthcare providers, 61 of whom were PCPs who treat patients with HFpEF and obesity. RESULTS: Half of patients (51%) with HFpEF reported waiting an average of 11 months to discuss their symptoms with a PCP; 11% then received their diagnosis from a PCP. PCPs initiated treatment and oversaw the management of HFpEF only 35% of the time, and 44% of PCPs discussed obesity treatment medication options with their patients. Only 20% of PCPs indicated they had received formal obesity management training, and 79% of PCPs indicated they would be interested in obesity management training and support. CONCLUSION: PCPs could play a valuable role in addressing obesity and referring patients with obesity and signs and symptoms of HFpEF to cardiologists. Increased awareness of HFpEF and its link to obesity may help PCPs more quickly identify and diagnose their patients with these conditions.

Heart failure with preserved ejection fraction (HFpEF) is a common form of heart failure. Many patients who have HFpEF also have obesity or excess weight. We wanted to understand the medical experience of patients with HFpEF and obesity and the role that primary care providers (PCPs) play in managing patients with these diseases. We surveyed 114 patients with HFpEF and obesity and 200 healthcare providers who treat patients with HFpEF and obesity, 61 of whom were PCPs. One-quarter of patients had a major heart-related event that led to their HFpEF diagnosis. Half of the patients said they had an initial discussion about HFpEF symptoms with a PCP, but only one in ten were diagnosed by a PCP. Few PCPs said they received obesity management training, but most were interested in receiving more obesity management training and support. PCPs play an important role in organizing care for patients with HFpEF and obesity. However, there is room to improve HFpEF awareness and access to obesity management tools and strategies among PCPs.

Insights into the interplay between gut microbiota and lipid metabolism in the obesity management of canines and felines.

Obesity is a prevalent chronic disease that has significant negative impacts on humans and our companion animals, including dogs and cats. Obesity occurs with multiple comorbidities, such as diabetes, hypertension, heart disease and osteoarthritis in dogs and cats. A direct link between lipid metabolism dysregulation and obesity-associated diseases has been implicated. However, the understanding of such pathophysiology in companion animals is limited. This review aims to address the role of lipid metabolism in various metabolic disorders associated with obesity, emphasizing the involvement of the gut microbiota. Furthermore, we also discuss the management of obesity, including approaches like nutritional interventions, thus providing novel insights into obesity prevention and treatment for canines and felines.

Seat Belt Injury and Efferent Loop Laceration Following a Single Anastomosis Duodenal Switch: A Case Report.

Blunt abdominal trauma patients who have had prior bariatric procedures may present a diagnostic and therapeutic challenge. The single anastomosis duodenal-ileal bypass with sleeve (SADI-S) is a modified duodenal switch procedure that is relatively uncommon. This case report describes a patient who previously underwent a SADI-S for the management of obesity and subsequently sustained a seat belt injury in a motor vehicle collision resulting in a laceration of the efferent loop. The patient presented with symptoms of acute abdominal pain and was diagnosed through imaging studies. Prompt surgical intervention was performed with resection and primary anastomosis of the damaged section of the jejunum, and repair of a large mesenteric laceration. We discuss the importance of early recognition and intraoperative decision-making in the case of this patient concerning her SADI-S.

Weight Loss Programs: Why Do They Fail? A Multidimensional Approach for Obesity Management.

PURPOSE OF REVIEW: Despite the prevalence of weight loss programs, their success rates remain discouraging, with around half of individuals regaining lost weight within two years. The primary objective of this review is to explore the factors contributing to the failure of weight loss programs and to provide insights into effective weight management strategies. RECENT FINDINGS: Factors contributing to the failure of weight loss programs include the impracticality of restrictive diets, potential metabolic impacts, limited focus on lifestyle changes, genetic predispositions, psychological influences, socioeconomic status, and medical conditions. A holistic approach considering these factors is crucial for safe and sustainable weight loss. Key findings indicate the importance of holistic approaches to weight management, including lifestyle modifications, medical interventions, and behavioral and psychological strategies. Effective weight loss strategies emphasize low-calorie, nutrient-rich diets, regular physical activity, and interventions tailored to individual needs. Combining multiple approaches offers the best chance of successful weight management and improved health outcomes. This review provides insights into the complexities of obesity management and the factors contributing to the failure of weight loss programs. It highlights the necessity of adopting a holistic approach that addresses dietary habits, physical activity, genetic factors, psychological well-being, and socioeconomic influences. Recommendations include implementing lifestyle modifications, medical interventions when necessary, and integrating behavioral and psychological support to achieve sustainable weight loss and mitigate the global health challenge posed by obesity.

Association of Body Mass Index and Central Obesity with Spinopelvic Alignment Parameters in a Chinese Population: A Prospective Study.

OBJECTIVE: The purpose of this study was to explore the impact of central obesity on spinal sagittal balance in adults aged 18 and older by examining correlations between waist circumference (WC) and abdominal circumference (AC) and spinopelvic alignment parameters. METHODS: This prospective cohort study included 350 adults aged 18 and older. Participants underwent whole-body biplanar radiography using the EOS imaging system. Spinal and pelvic parameters were measured and correlated with body mass index, WC, and AC. Statistical analyses included one-way analysis of variance, Wilcoxon rank-sum tests for data with nonhomogeneous variances, and chi-squared tests for categorical data. Intra-rater and inter-rater reliability were assessed using intraclass correlation coefficients, with subsequent analyses to explore correlations between body measurements and spinal parameters. RESULTS: The study found significant correlations between increased WC and AC and changes in spinopelvic parameters. However, obesity did not uniformly influence all sagittal alignment parameters. Significant variations in spinal measurements indicate that central obesity plays a role in altering spinal stability and alignment. CONCLUSIONS: The findings highlight the impact of central obesity on spinal alignment and emphasize the importance of considering central obesity in clinical assessments of spinal pathologies. Further research is essential to better understand the relationship between obesity, spinal sagittal balance, and related health conditions.

ACTION-FRANCE: Insights into Perceptions, Attitudes, and Barriers to Obesity Management in France.

Background/Objectives: ACTION-FRANCE (Awareness, Care, and Treatment In Obesity maNagement in France) aims to identify the perceptions, attitudes, behaviors, and potential barriers to effective obesity management in France and guide collaborative actions. Methods: ACTION-FRANCE is a cross-sectional survey of people with obesity (PwO) and healthcare professionals (HCPs) in France. The PwO and HCP survey questionnaire periods ran from 27 September 2022 to 1 February 2023 and from 19 December 2022 to 31 March 2023, respectively. Results: The study, encompassing 1226 PwO and 166 HCPs, reveals a shared recognition of obesity as a chronic condition. However, despite being requested by most PwO, weight-related discussions are surprisingly infrequent, leading to delayed diagnosis and care. PwO and HCPs held different views as to why: HCPs often attributed it to PwO's lack of motivation or disinterest, whereas PwO avoided them because they felt weight management was their own responsibility and were uncomfortable discussing it. When weight was discussed, primarily with general practitioners (GPs), discussions mostly focused on physical activity and diet. However, results identified the strong psychosocial impact of obesity: 42% of respondents reported anxiety/depressive symptoms, and many more hesitated to engage in certain social activities because of their weight. Psychotherapy was only discussed by 55% of HCPs. Pharmaceutical options were also rarely discussed (19.5% of HCPs), though 56.1% of PwO reported they would want to. Conclusions: HCPs' and PwO's perceptions differed significantly and need to converge through enhanced communication. A holistic approach, integrating comprehensive training for GPs and recognizing psychological comorbidities, would help to bridge perceptual gaps effectively and foster more empathetic and effective patient care.

Medical weight loss in older persons with obesity.

The prevalence of individuals with obesity or overweight has steadily increased over the past decades both worldwide, and in the United States. This trend is also evident in the older adult population, which has experienced a continuous rise in the number of individuals with overweight or obesity. This is relevant due to the impact of obesity in older adults' quality of life, physical function, morbidity, and healthcare costs. This review aims to provide practical guidance and currently available approaches for healthcare professionals in managing this population. Both non-pharmacological methods such as intensive behavioural therapy, nutritional interventions, and physical activity, as well as anti-obesity medications, are discussed, with a focus on their potential positive and negative effects in older adults. Additionally, bariatric therapy is evaluated, including current procedures available and the associated results and risks in the older population.

A systematic review and meta-analysis of environmental contaminant exposure impacts on weight loss and glucose regulation during calorie-restricted diets in preclinical studies: Persistent organic pollutants may impede glycemic control.

Epidemiological evidence links chemical exposure with type 2 diabetes (T2DM) risk and prevalence. Chemical exposure may therefore also limit success of weight loss or restoration of glycemic control during calorie restricted diets. Few human studies examine this hypothesis. This systematic review and clustered meta-analysis examines preclinical evidence that exposure to anthropogenic environmental contaminants impedes weight loss and resumption of glycemic control during calorie restriction. Of five eligible papers from 212 unique citations, four used C57BL/6 mice and one used Sprague Dawley rats. In four the animals received high fat diets to induce obesity and impaired glycemic control. All examined persistent organic pollutants (POPs). Polychlorinated biphenyl (PCB) 77 exposure did not affect final mass (standardised mean difference (SMD) = -0.35 [-1.09, 0.39]; n = 5 (experiments); n = 3 (papers)), or response to insulin in insulin tolerance tests (SMD = -1.54 [-3.25, 0.16] n = 3 (experiments); n = 2 (papers)), but impaired glucose control in glucose tolerance tests (SMD = -1.30 [-1.96, -0.63]; n = 6 (experiments); n = 3 (papers)). The impaired glycemic control following perfluoro-octane sulphonic acid (PFOS) exposure and enhanced mass loss following dichlorodiphenyltrichloroethane (DDT) exposure have not been replicated. Animal studies thus suggest some chemical groups, especially PCB and PFOS, could impair glucose control management during calorie restriction, similar to conclusions from limited existing clinical studies. We discuss the research that is urgently required to inform weight management services that are now the mainstay prevention initiative for T2DM.

Obesity-induced tissue alterations resist weight loss: A mechanistic review.

Interventions aimed at weight control often have limited effectiveness in combating obesity. This review explores how obesity-induced dysfunction in white (WAT) and brown adipose tissue (BAT), skeletal muscle, and the brain blunt weight loss, leading to retention of stored fat. In obesity, increased adrenergic stimulation and inflammation downregulate ß-adrenoreceptors and impair catecholaminergic signalling in adipocytes. This disrupts adrenergic-mediated lipolysis, diminishing lipid oxidation in both white and brown adipocytes, lowering thermogenesis and blunting fat loss. Emerging evidence suggests that WAT fibrosis is associated with worse weight loss outcomes; indeed, limiting collagen and laminin-α4 deposition mitigates WAT accumulation, enhances browning, and protects against high-fat-diet-induced obesity. Obesity compromises mitochondrial oxidative capacity and lipid oxidation in skeletal muscle, impairing its ability to switch between glucose and lipid metabolism in response to varying nutrient levels and exercise. This dysfunctional phenotype in muscle is exacerbated in the presence of obesity-associated sarcopenia. Additionally, obesity suppresses sarcolipin-induced sarcoplasmic reticulum calcium ATPase (SERCA) activation, resulting in reduced oxidative capacity, diminished energy expenditure, and increased adiposity. In the hypothalamus, obesity and overnutrition impair insulin and leptin signalling. This blunts central satiety signals, favouring a shift in energy balance toward energy conservation and body fat retention. Moreover, both obese animals and humans demonstrate impaired dopaminergic signalling and diminished responses to nutrient intake in the striatum, which tend to persist after weight loss. This may result in enduring inclinations toward overeating and a sedentary lifestyle. Collectively, the tissue adaptations described pose significant challenges to effectively achieving and sustaining weight loss in obesity.

Clinical effectiveness and predictors of response to topiramate plus lifestyle modification in youth with obesity seen in a weight management clinical setting.

Introduction: Obesity affects approximately 20% of U.S. youth. Anti-obesity medications (AOMs) are promising lifestyle modification adjuncts for obesity treatment, and topiramate is commonly prescribed in pediatric weight management clinics. It is important to determine "real-world" effectiveness of AOMs and, given shifts towards personalized approaches, characteristics potentially predicting better or worse response. We therefore sought to describe clinical effectiveness from topiramate plus lifestyle modification, and to determine if baseline phenotypic characteristics are associated with better or worse response. Methods: We performed a retrospective cohort study (2012-2020) among youth (<18 years old) followed in a U.S. academic-based weight management clinic. Baseline characteristics (i.e., body mass index (BMI), liver function tests, eating-related behaviors) and outcomes (%BMI of 95th percentile (%BMIp95), BMI, percent %BMI change, weight) were determined through review of electronic health records and clinic intake survey data. Results: Among 282 youth prescribed topiramate plus lifestyle modifications (mean baseline age 12.7 years, %BMIp95 144%), %BMIp95 and percent BMI change were statistically significantly reduced at each time point (1.5-, 3-, 6-, and 12-month %BMIp95 reductions: -2.2, -3.9, -6.6, and -9.3 percentage points, respectively; percent BMI reduction: -1.2%, -1.9%, -3.2%, and -3.4%, respectively; all p<0.01). Considering multiple comparisons, no baseline characteristics statistically significantly predicted response at any time point. Conclusions: We found that topiramate plus lifestyle modification reduced %BMIp95 and BMI among youth in a weight management clinical setting, and that no baseline characteristics evaluated were associated with response. These results should be considered preliminary given the observational nature of this study, and prospective studies are needed to further characterize clinical effectiveness and identify and confirm potential predictors of response.