Long-term Weight Management Research Articles

Why does GLP-1 agonist combined with GIP and/or GCG agonist have greater weight loss effect than GLP-1 agonist alone in obese adults without type 2 diabetes?

Obesity is a chronic condition demanding effective treatment strategies, among which pharmacotherapy plays a critical role. As glucagon-like peptide-1 (GLP-1) agonist approved by the Food and Drug Administration (FDA) for long-term weight management in adults with obesity, liraglutide and semaglutide have great weight loss effect through reducing food intake and delaying gastric emptying. The emergence of unimolecular polypharmacology, which utilizes single molecules to simultaneously target multiple receptors or pathways, marked a revolutionary improvement in GLP-1-based obesity pharmacotherapy. The dual agonist tirzepatide activates both GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors and has shown enhanced potency for weight loss compared to conventional GLP-1 mono agonist. Furthermore, emerging data suggests that unimolecular GLP-1/glucagon (GCG) dual agonist, as well as GLP-1/GIP/GCG triple agonist, may offer superior weight loss efficacy over GLP-1 agonist. This review summarizes the comprehensive mechanisms underlying the pronounced advantages of GLP-1/GIP dual agonist, GLP-1/GCG dual agonist and GLP-1/GIP/GCG triple agonist over GLP-1 mono agonist in weight reduction in obese adults without type 2 diabetes. A deeper understanding of these unimolecular multitargeting GLP-1-based agonists will provide insights for their clinical application and guide the development of new drugs for obesity treatment.

Adipose tissue retains an epigenetic memory of obesity after weight loss.

Reducing body weight to improve metabolic health and related comorbidities is a primary goal in treating obesity1,2. However, maintaining weight loss is a considerable challenge, especially as the body seems to retain an obesogenic memory that defends against body weight changes3,4. Overcoming this barrier for long-term treatment success is difficult because the molecular mechanisms underpinning this phenomenon remain largely unknown. Here, by using single-nucleus RNA sequencing, we show that both human and mouse adipose tissues retain cellular transcriptional changes after appreciable weight loss. Furthermore, we find persistent obesity-induced alterations in the epigenome ofmouse adipocytes thatnegatively affect their function and response to metabolic stimuli. Mice carrying this obesogenic memory show accelerated rebound weight gain, and the epigenetic memory can explain future transcriptional deregulation in adipocytes in response to further high-fat diet feeding. In summary, our findings indicate the existence of an obesogenic memory, largely on the basis of stable epigenetic changes, in mouse adipocytes and probably other cell types. These changes seem to prime cells for pathological responses in an obesogenic environment, contributing to the problematic 'yo-yo' effect often seen with dieting. Targeting these changes in the future could improve long-term weight management and health outcomes.

A Systematic Review Exploring Dietary Behaviors, Psychological Determinants and Lifestyle Factors Associated with Weight Regain After Bariatric Surgery.

Weight regains after bariatric surgery presents a significant challenge to long-term weight management and overall health outcomes. While clinical and surgical factors influencing bariatric outcomes have been extensively reviewed, there remains a notable gap in understanding how behavioral factors-specifically dietary habits, psychological influences, and lifestyle choices-impact long-term weight maintenance. This systematic review addresses this gap, highlighting the unique role of these behavioral factors in sustaining weight loss post-bariatric surgery. This systematic review aims to explore the behavioral factors-including dietary, psychological, and lifestyle influences-associated with weight regain after bariatric surgery. A comprehensive search was conducted across multiple databases, focusing on peer-reviewed articles published in English. We included observational studies exclusively focused on adults who experienced weight regain after bariatric surgery, with an emphasis on behavioral factors. Searches were conducted in MEDLINE via PubMed, Embase, Web of Science, Scopus, and Google Scholar, with the last search completed on 10 July 2024. Studies published within the past 10 years were considered. The Joanna Briggs Institute (JBI) critical appraisal tool for cross-sectional studies was used to assess the risk of bias. A total of 16 studies met the inclusion criteria: 12 cross-sectional studies, 3 cohort studies, and 1 in-depth interview study. The review found inconsistencies in the definitions of weight regain across studies. Nonetheless, three primary behavioral factors were identified as potentially contributing to weight regain: dietary non-adherence and eating patterns, psychological determinants, and lifestyle behaviors. Dietary non-adherence included high-calorie food consumption, excessive intake of sweets, carbohydrates, and sweetened beverages, and low protein intake. Psychological factors such as depression, anxiety, emotional eating, and binge eating were prevalent among individuals experiencing weight regain. Lifestyle behaviors, including physical inactivity, smoking, and sedentary habits, also played significant roles. Post-bariatric weight management is multifaceted, necessitating a comprehensive approach that addresses dietary, psychological, and lifestyle factors. Most studies on behavioral factors linked to weight regain were cross-sectional with small sample sizes, limiting the ability to infer causality. Future research should include detailed information on dietary adherence, standardized tools to assess physical activity and sedentary behavior, and validated measures for psychological health. Tailored interventions and continuous support from healthcare professionals are essential for maximizing the effectiveness of bariatric surgery, promoting sustainable weight loss, and enhancing overall health outcomes.

Incretin-Based Therapies and Lifestyle Interventions: The Evolving Role of Registered Dietitian Nutritionists in Obesity Care

The emergence of incretin-based therapies, specifically glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and glucose-dependent insulinotropic polypeptide (GIP), as a new class of obesity medications, is dramatically changing obesity care. Use of these medications, known categorically as anti-obesity medications, as part of comprehensive obesity management is associated with significantly greater weight loss and health benefits than found with earlier generation obesity medications. The outcomes reported from medication trials were often achieved in conjunction with lifestyle counseling sessions by a registered dietitian nutritionist (RDN) or other qualified health care professional. Research demonstrates that evidence-based obesity care should incorporate lifestyle interventions. Counseling by a RDN, paired with incretin-based therapies, can play a critical role in supporting adherence to the medication regimen, preventing and managing side effects, adequate nutrient intake, and establishment of lifestyle behaviors for long-term weight and health management. To date, minimal research has been reported on the impact of incretin-based therapies on food and nutrient intake. Until that research is conducted, RDNs and other health professionals can apply knowledge and experience from clients who have undergone other intensive treatments. This article provides considerations for lifestyle interventions, with a focus on medical nutrition therapy (MNT) provided by RDNs, for adults prescribed incretin-based therapies. RDNs have the education and training to provide MNT for people with overweight or obesity, as well as lifestyle counseling on physical activity, stress management, sleep hygiene, goal setting, and other behaviors associated with positive health outcomes. RDNs have a critical role in the integration of incretin-based therapies into obesity management.

Impact of Exercise Training at Maximal Fat Oxidation Intensity on Metabolic and Epigenetic Parameters in Patients with Overweight and Obesity: Study Protocol of a Randomized Controlled Trial.

Background: Exercise is an essential pillar for human health, as it contributes to physical, mental, and emotional well-being. Well-recognized international organizations, such as the World Health Organization, advocate for integrating exercise into healthy lifestyles, recognizing its importance in disease prevention and improving quality of life. However, despite the consensus on its value, there is no universal agreement on specific prescriptions for vulnerable groups, highlighting the need for personalized approaches that consider the unique characteristics and needs of everyone. Emerging studies have demonstrated that exercise training performed at the intensity that elicits maximal fat oxidation improves insulin sensitivity, cardiorespiratory fitness, and body composition in patients with obesity, making it a highly effective strategy for long-term weight management and metabolic health in this specific population. Methods: The present study protocol settles the basis for a 16-week randomized clinical trial based on exercise prescription at the maximal fat oxidation rate combined with resistance training in young individuals with overweight and obesity. Expected Results: This study will elucidate how FatMax, with or without resistance exercises, can enhance metabolic flexibility, increase fat oxidation, and improve body composition, evaluating changes in biochemical parameters (cholesterol, glucose, triglycerides, and inflammatory markers), metabolic biomarkers (determination of fat and carbohydrate utilization rates during rest and exercise), and epigenetic indicators (focusing on microRNAs associated with adipogenesis, inflammation, and fat metabolism). ClinicalTrials.gov identification number: NCT06553482 (FatMax Training on Metabolic and Epigenetic Parameters).

Obesity Medications and Their Impact on Cardiovascular Health: A Narrative Review.

Obesity is a major global issue linked to cardiovascular diseases (CVDs). While lifestyle changes are the primary treatment, medications are often required for long-term weight management and reducing risk in patients with obesity. The cardiovascular effects of many obesity medications are still being studied. This review examines the cardiovascular impact of commonly prescribed obesity medications, focusing on their mechanisms, effectiveness, and safety. A review of the literature was conducted to evaluate the cardiovascular effects of these drugs, including their impact on major cardiovascular outcomes, cholesterol, blood pressure, and other heart-related factors. Some medications, like glucagon-like peptide-1 receptor agonists (GLP-1 RAs), show cardiovascular benefits, while others like orlistat have a lesser effect. Medications such as naltrexone-bupropion and phentermine-topiramate offer weight loss but still require further review for their cardiovascular safety. Data on setmelanotide's long-term effects are limited. Obesity medications differ in their effects on cardiovascular health, with some offering more consistent benefits. More studies are needed to fully understand their long-term risks and benefits, but combining medication with lifestyle changes remains key to improving both weight and heart health.

New Obesity Treatment Agent: β-Caryophyllene

Abstract: Obesity is a pressing global public health challenge, recognized as a major risk factor for chronic diseases, such as diabetes, cardiovascular conditions, and cancer. The rising obesity rates necessitate effective and safe therapeutic interventions. Despite the availability of FDA-approved drugs for long-term weight management, these pharmacological treatments often entail significant side effects and high costs, leading to low patient adherence. Consequently, there is an increasing focus on natural anti-obesity agents. β-caryophyllene (BCP) has emerged as a promising candidate, owing to its broad pharmacological properties. This review critically examines recent advancements in understanding BCP's anti-obesity effects, encompassing in vitro, animal, and clinical studies. Key mechanisms by which BCP exerts its effects include modulation of gut microbiota, enhancement of energy expenditure, regulation of metabolic enzymes, and inhibition of lipid synthesis and absorption. These insights lay the groundwork for the potential development of BCP-based dietary supplements or pharmaceuticals aimed at combating obesity.

Efficacy and safety of once-weekly tirzepatide for weight management compared to placebo: An updated systematic review and meta-analysis including the latest SURMOUNT-2 trial.

Tirzepatide, a newly developed dual glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, has received approval for treating type 2 diabetes (T2D) and is currently being studied for its potential in long-term weight control. We aim to explore the safety and efficacy of once-weekly subcutaneous tirzepatide for weight loss in T2D or obese patients. A comprehensive search was performed on various databases including PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov from inception up to April 29, 2024, to identify randomized controlled trials (RCTs) that assessed the efficacy of once-weekly tirzepatide compared to a placebo in adults with or without T2D. The mean difference (MD) and risk ratio (RR) were calculated for continuous and dichotomous outcomes, respectively. The risk of bias was evaluated using the RoB-2 tool (Cochrane), while the statistical analysis was conducted utilizing RevMan 5.4.1 software. Seven RCTs comprising 4795 individuals ranging from 12 to 72 weeks were identified. Compared to the placebo group, tirzepatide at doses of 5, 10, and 15 mg demonstrated significant dose-dependent weight loss. The mean difference (MD) in the percentage change in body weight (BW) was -8.07% (95% CI -11.01, -5.13; p < 0.00001), -10.79% (95% CI -13.86, -7.71; p < 0.00001), and -11.83% (95% CI -14.52, -9.14; p < 0.00001), respectively. Additionally, the MD in the absolute change in BW was -7.5 kg (95% CI -10.9, -4.1; p < 0.0001), -11.0 kg (95% CI -16.9, -5.2; p = 0.0002), and -11.5 kg (95% CI -16.2, -6.7; p < 0.00001), for the 5, 10, and 15 mg doses, respectively. All three doses of tirzepatide also significantly reduced body mass index and waist circumference. Furthermore, it led to a greater percentage of patients experiencing weight loss exceeding 5, 10, 15, 20, and 25%. Moreover, tirzepatide showed great success in reducing blood pressure, blood sugar levels, and lipid profiles. In terms of safety, gastrointestinal side effects were the most frequently reported adverse events in all three doses of tirzepatide groups, which were generally mild-to-moderate and transient. Tirzepatide treatment could lead to remarkable and sustained weight loss that is well-tolerated and safe, representing a novel and valuable therapeutic strategy for long-term weight management.

Obesity pharmacotherapy in older adults: a narrative review of evidence.

The prevalence of obesity in older adults (people aged >60 years) is increasing in line with the demographic shift in global populations. Despite knowledge of obesity-related complications in younger adults (increased risk of type 2 diabetes, liver and cardiovascular disease and malignancy), these considerations may be outweighed, in older adults, by concerns regarding weight-loss induced reduction in skeletal muscle and bone mass, and the awareness of the 'obesity paradox'. Obesity in the elderly contributes to various obesity-related complications from cardiometabolic disease and cancer, to functional decline, worsening cognition, and quality of life, that will have already suffered an age-related decline. Lifestyle interventions remain the cornerstone of obesity management in older adults, with emphasis on resistance training for muscle strength and bone mineral density preservation. However, in older adults with obesity refractory to lifestyle strategies, pharmacotherapy, using anti-obesity medicines (AOMs), can be a useful adjunct. Recent evidence suggests that intentional weight loss in older adults with overweight and obesity is effective and safe, hence a diminishing reluctance to use AOMs in this more vulnerable population. Despite nine AOMs being currently approved for the treatment of obesity, limited clinical trial evidence in older adults predominantly focuses on incretin therapy with glucagon-like peptide-1 receptor agonists (liraglutide, semaglutide, and tirzepatide). AOMs enhance weight loss and reduce cardiometabolic events, while maintaining muscle mass. Future randomised controlled trials should specifically evaluate the effectiveness of novel AOMs for long-term weight management in older adults with obesity, carefully considering the impact on body composition and functional ability, as well as health economics.

Obesity medications: A narrative review of current and emerging agents

The aim of this narrative review is to synthesize the available data describing the efficacy and safety of medications approved for obesity management and to provide an overview of upcoming agents in development.A literature search of PubMed, Medline, and Embase databases identified relevant articles describing medications approved in the U.S., Australia, U.K., and/or Europe. Papers were selected based on relevance and originality, with phase 3 clinical trials and meta-analyses preferentially included.Six medications are widely approved for long-term weight management in conjunction with lifestyle interventions in people with body mass index (BMI) ≥30 ​kg/m2 or BMI ≥27 ​kg/m2 and at least one medical condition related to excess weight. Compared with lifestyle interventions alone, all medications approved for obesity management are more effective for long-term weight loss and improvements in cardiometabolic risk factors. Older obesity medications are associated with mean weight losses in the range of 5–10%. The new generation of agents, including the injectable incretin analogues semaglutide and tirzepatide are associated with sustained mean weight reductions of 15–20%, along with substantial benefits on a range of health outcomes. Several novel agents are under development, with multi-hormone receptor agonists and oral formulations likely to become available in the coming years.As effective treatment options expand, cost and availability will need to be addressed to enable equitable access to treatment. Other important challenges for clinical practice and research include the need for long-term strategies to prevent and manage weight regain and loss of lean muscle and bone mineral density.

Low-Carbohydrate Diet Macronutrient Quality and Weight Change

The associations of low-carbohydrate diets (LCDs) with long-term weight management remains unclear, and the source and quality of macronutrients within LCDs are less explored. To prospectively examine associations between changes in LCD indices and weight change among US adults. This prospective cohort study included initially healthy participants at baseline from the Nurses' Health Study (NHS; 1986-2010), Nurses' Health Study II (NHSII; 1991-2015), and Health Professionals Follow-up Study (HPFS; 1986-2018). Data analysis was performed between November 2022 and April 2023. Five LCD indices were examined: (1) a total LCD (TLCD) emphasizing overall lower carbohydrate intake; (2) an animal-based LCD (ALCD) that emphasized animal-sourced protein and fat; (3) a vegetable-based LCD (VLCD) that emphasized plant-sourced protein and fat; (4) a healthy LCD (HLCD) emphasizing less refined carbohydrates, more plant protein, and healthy fat; and (5) an unhealthy LCD (ULCD) emphasizing less healthful carbohydrates, more animal protein, and unhealthy fat. The outcome of interest was 4-year changes in self-reported body weight. A total of 123 332 participants (mean [SD] age, 45.0 [9.7] years; 103 320 [83.8%] female) were included in this study. The median carbohydrate intake (as a percentage of energy) of the highest quintiles of TLCD score at baseline ranged from 38.3% in HPFS to 40.9% in NHSII. Mean weight gain over 4-year intervals among participants varied from 0.8 kg in the HPFS to 1.8 kg in the NHSII. After adjusting for demographics and baseline and concomitant changes of selected lifestyle factors, each 1-SD increase in TLCD score was associated with 0.06 (95% CI, 0.04-0.08) kg more weight gain over the 4-year periods. Similarly, participants gained 0.13 (95% CI, 0.11 to 0.14) kg per each 1-SD increase in ALCD score and 0.39 (95% CI, 0.37 to 0.40) kg per each 1-SD change in ULCD score. In contrast, each 1-SD increase in VLCD score was associated with 0.03 (95% CI, 0.01 to 0.04) kg less weight gain, and each 1-SD increase in HLCD score was associated with 0.36 (95% CI, 0.35 to 0.38) kg less weight gain. The associations were more pronounced among obese individuals (per 1-SD increase in HLCD score: BMI ≥30, 0.88 [95% CI, 0.80, 0.97] kg less weight gain; BMI <25, 0.23 [95% CI, 0.20, 0.26] kg less weight gain; P for interaction < .001). These findings suggest that the quality of LCDs may play a critical role in modulating long-term weight change. Only LCDs that emphasized high-quality protein, fat, and carbohydrates from whole grains and other plant-based foods were associated with less weight gain.

Time-Restricted Eating in Community-Dwelling Adults: Correlates of Adherence and Discontinuation in a Cross-Sectional Online Survey Study

BackgroundTime-restricted eating (TRE), a type of intermittent fasting in which all daily calories are consumed within a window of ≤12 hours, is hypothesized to promote long-term weight management because of its relative simplicity. ObjectiveThis study reports correlates of adherence among community-dwelling adults currently or formerly following a TRE dietary strategy. DesignA 25-minute cross-sectional online survey was developed, including questions about TRE perceptions, behaviors, motivators and drivers, and demographics. The survey was administered in February 2021 via Prolific, an online platform for sample recruitment and survey dissemination. ParticipantsEligibility criteria included US adult ages 18+ who currently or formerly (past 3 months) followed TRE (ie, consumed all daily calories within a window of ≤12 hours) for a minimum of 1 week. Statistical Analysesχ2 tests and analysis of covariance (ANCOVA; adjusting for sex and age) compared responses between current and former followers. ResultsCurrent followers (n = 296, mean [SD]: 34.2 ± 12.2y) were older than former followers (n = 295, mean [SD]: 31.1 ± 10.9 y) and practiced TRE for longer (median: 395 vs 90 days, P < 0.001). Current followers reported more success with meeting TRE goals (P ≤ 0.015), were less likely to report TRE concerns (P < 0.001), and more likely to report TRE satisfaction (P < 0.001). Four TRE motivators were more important among current (vs former) followers: weight maintenance, health (not weight), improved sleep, and preventing disease (P ≤ 0.017); weight loss was more important among former (vs current) followers (P = 0.003). Among adherence drivers, ability to work from home and the impact of COVID-19 were reported as more helpful for TRE adherence among current compared with former followers (P ≤ 0.028). ConclusionsTRE motivators and drivers differed between current and former followers; interventions tailored to individuals’ preferences and circumstances may benefit TRE adherence.

FRI247 Case Of Metabolic Resolution Of Non-classic Congenital Adrenal Hyperplasia Post Roux-En-Y Gastric Bypass

Abstract Disclosure: K.G. Romo: None. S. Shu: None. M. Gabriel: None. S. Bhamre: None. Q.Z. Iqbal: None. A.A. Noor: None. G.I. Uwaifo: None. Background: Non-classic congenital adrenal hyperplasia (NCCAH) is an autosomal recessive disorder resulting from loss of function mutations of the 21-hydroxylase gene. It is characterized by mild cortisol deficiency, excess ACTH production, and androgen excess, often with various features of dysmetabolic syndrome. Elective bariatric surgery is one of the most effective long-term management strategies for morbid and complicated obesity. This case presents a woman with NCCAH and complicated morbid obesity who s/p Roux-en-Y Gastric Bypass (RYGB) had metabolic resolution of NCCAH and no longer required glucocorticoid (GC) therapy. Clinical Case: A 34-year-old G1P1 woman with NCCAH on glucocorticoid therapy, treated hypothyroidism with thyroid nodular disease, dyslipidemia, and morbid obesity (pre-RYGB BMI 60-69.9) initially presented to endocrinology on account of hirsutism and secondary amenorrhea attributed to PCOS. Work-up then confirmed diagnosis of NCCAH with 21-hydroxylase genetic testing showing deletion of one copy of CYP21A2 and the pathogenic variant p.V282L in the remaining copy. Outside the peripartum period, she was managed with OCP therapy, spironolactone, and metformin. She was additionally prescribed GC therapy of hydrocortisone 10mg TID following her diagnosis of NCCAH. She subsequently became pregnant unexpectedly. Post-partum course was complicated by significant weight gain, which led her to seek elective bariatric surgery for long-term weight management. At 5 months post-op, she had a weight deficit of ∼100lbs. Although she self-discontinued GC therapy due to fear of weight gain, her amenorrhea resolved, her hirsutism significantly improved, and lab testing revealed normalization of all NCCAH markers, including ACTH, 17-OHP, and androstenedione. Thus, GC therapy was not restarted. At 11 months post-op and still off GC therapy, she had a total weight deficit of ∼160lbs and continued metabolic resolution of NCCAH markers. Conclusions: This case presents a patient with NCCAH and morbid obesity who no longer required GC therapy post-RYGB. Presently, GC therapy remains the only available treatment for CAH; however, long-term GC therapy has the potential for myriad possible complications and side effects. Our case presents elective bariatric surgery as a potential and unique treatment option for patients with classic or non-classic CAH who have associated morbid obesity. The exact pathophysiologic basis for this effect and its potential role in long-term management of appropriate CAH patients requires further in-depth study. Presentation: Friday, June 16, 2023

Weight Loss Promotion in Individuals with Obesity through Gut Microbiota Alterations with a Multiphase Modified Ketogenic Diet.

The occurrence of obesity and related metabolic disorders is rising, necessitating effective long-term weight management strategies. With growing interest in the potential role of gut microbes due to their association with responses to different weight loss diets, understanding the mechanisms underlying the interactions between diet, gut microbiota, and weight loss remains a challenge. This study aimed to investigate the potential impact of a multiphase dietary protocol, incorporating an improved ketogenic diet (MDP-i-KD), on weight loss and the gut microbiota. Using metagenomic sequencing, we comprehensively analyzed the taxonomic and functional composition of the gut microbiota in 13 participants before and after a 12-week MDP-i-KD intervention. The results revealed a significant reduction in BMI (9.2% weight loss) among obese participants following the MDP-i-KD intervention. Machine learning analysis identified seven key microbial species highly correlated with MDP-i-KD, with Parabacteroides distasonis exhibiting the highest response. Additionally, the co-occurrence network of the gut microbiota in post-weight-loss participants demonstrated a healthier state. Notably, metabolic pathways related to nucleotide biosynthesis, aromatic amino acid synthesis, and starch degradation were enriched in pre-intervention participants and positively correlated with BMI. Furthermore, species associated with obesity, such as Blautia obeum and Ruminococcus torques, played pivotal roles in regulating these metabolic activities. In conclusion, the MDP-i-KD intervention may assist in weight management by modulating the composition and metabolic functions of the gut microbiota. Parabacteroides distasonis, Blautia obeum, and Ruminococcus torques could be key targets for gut microbiota-based obesity interventions.

Carbohydrate-insulin model: does the conventional view of obesity reverse cause and effect?

Conventional obesity treatment, based on the First Law of Thermodynamics, assumes that excess body fat gain is driven by overeating, and that all calories are metabolically alike in this regard. Hence, to lose weight one must ultimately eat less and move more. However, this prescription rarely succeeds over the long term, in part because calorie restriction elicits predictable biological responses that oppose ongoing weight loss. The carbohydrate-insulin model posits the opposite causal direction: overeating doesn't drive body fat increase; instead, the process of storing excess fat drives overeating. A diet high in rapidly digestible carbohydrates raises the insulin-to-glucagon ratio, shifting energy partitioning towards storage in adipose, leaving fewer calories for metabolically active and fuel sensing tissues. Consequently, hunger increases, and metabolic rate slows in the body's attempt to conserve energy. A small shift in substrate partitioning though this mechanism could account for the slow but progressive weight gain characteristic of common forms of obesity. From this perspective, the conventional calorie-restricted, low-fat diet amounts to symptomatic treatment, failing to target the underlying predisposition towards excess fat deposition. A dietary strategy to lower insulin secretion may increase the effectiveness of long-term weight management and chronic disease prevention. This article is part of a discussion meeting issue 'Causes of obesity: theories, conjectures and evidence (Part II)'.

INTEGRATION OF PHYSIOTHERAPY IN THE INSTRUCTIONAL-EDUCATIONAL PROCESS IN THE CORRECTION OF WEIGHT STATUS IN CHILDREN

The prevalence of overweight and obesity in children in the Republic of Moldova has increased dramatically in recent decades. And data from the Summary Report of the Health Behaviour Assessment Study of School-Aged Children (2014) shows that 11% of children are overweight, including 2.2% - obese. Recovery and correction of weight status in overweight and obese children requires a comprehensive approach involving dietary correction, regular physical activity, and behavioural changes, with a focus on long-term weight management rather than short-term extreme weight reduction. Recovery programs should incorporate reasonable weight loss goals, dietary correction, activity management and physical activity into both the instructional process and daily physical activity. Integrating physiotherapy into the educational instructional process is the modern approach and focuses on assessment, action planning, implementation, reassessment, modification, and discharge when goals are achieved. Subjects included in the study were 10 children with overweight, aged 12 - 13, who study in the Theoretical High School "Mihail Sadoveanu", Chisinau and at the Rehabilitation centre Kinetica. The period from September to May 2021 - 2022.

Effects of a Web-Based Lifestyle Intervention on Weight Loss and Cardiometabolic Risk Factors in Adults With Overweight and Obesity: Randomized Controlled Clinical Trial.

The high proportion of people with overweight and obesity has become a worldwide problem in recent decades, mainly due to health consequences, such as cardiovascular diseases, neoplasia, and type 2 diabetes mellitus. Regarding effective countermeasures, the digitization of health services offers numerous potentials, which, however, have not yet been sufficiently evaluated. Web-based health programs are becoming increasingly interactive and can provide individuals with effective long-term weight management support. The purpose of this randomized controlled clinical trial was to evaluate the effectiveness of an interactive web-based weight loss program on anthropometric, cardiometabolic, and behavioral variables and to compare it with a noninteractive web-based weight loss program. The randomized controlled trial included people who were aged between 18 and 65 years (mean 48.92, SD 11.17 years) and had a BMI of 27.5 to 34.9 kg/m2 (mean 30.71, SD 2.13 kg/m2). Participants (n=153) were assigned to either (1) an interactive and fully automated web-based health program (intervention) or (2) a noninteractive web-based health program (control). The intervention program focused on dietary energy density and allowed for dietary documentation with appropriate feedback on energy density and nutrients. The control group only received information on weight loss and energy density, but the website did not contain interactive content. Examinations were performed at baseline (t0), at the end of the 12-week intervention (t1), and at 6 months (t2) and 12 months (t3) thereafter. The primary outcome was body weight. The secondary outcomes were cardiometabolic variables as well as dietary and physical activity behaviors. Robust linear mixed models were used to evaluate the primary and secondary outcomes. The intervention group showed significant improvements in anthropometric variables, such as body weight (P=.004), waist circumference (P=.002), and fat mass (P=.02), compared with the control group over the course of the study. The mean weight loss after the 12-month follow-up was 4.18 kg (4.7%) in the intervention group versus 1.29 kg (1.5%) in the control group compared with the initial weight. The results of the nutritional analysis showed that the energy density concept was significantly better implemented in the intervention group. Significant differences in cardiometabolic variables were not detected between the 2 groups. The interactive web-based health program was effective in reducing body weight and improving body composition in adults with overweight and obesity. However, these improvements were not associated with relevant changes in cardiometabolic variables, although it should be noted that the study population was predominantly metabolically healthy. German Clinical Trials Register DRKS00020249; https://drks.de/search/en/trial/DRKS00020249. RR2-10.3390/ijerph19031393.

Exploring the Impact of the Gut Microbiome on Obesity and Weight Loss: A Review Article.

The global obesity pandemic has prompted efforts to search for novel intervention options, including maximizing the health benefits of certain gut microbes and their metabolic byproducts. Our increased understanding ofgut microbiota can potentiallylead to revolutionary advancements in weight management and general well-being. We studied the association between gut microbiota and obesity, as well as the possible benefits of probiotics, prebiotics, and synbiotics in the prevention and management of obesity in this review. We observed a relationship between themetabolism of nutrients, energy consumption, and gut flora. Numerous mechanisms, including the synthesis of short-chain fatty acids, hormone stimulation, and persistent low-grade inflammation, have been postulated to explain the role of gut bacteria in the etiology of obesity. It has been discovered that the diversity and composition of the intestinal microbiome vary in response to various forms of obesity therapy, which raises concerns about the potential impact of these changes on weight loss. According to research, probiotics, prebiotics, and synbiotics may alter the release of hormones, neurotransmitters, and inflammatory factors, thereby diminishing the stimuli of food consumption that lead to weight gain. More clinical research is required to determine the optimal probiotic, prebiotic, and synbiotic supplementation dosages, formulations, and regimens for long-term weight management and to determine how different gastrointestinal microbiome bacterial species may influence weight gain.

Exploring Approved Medications and the Promise of Phase 3 Clinical Trials: Anti-Obesity Drugs in the Sky and on the Horizon.

Obesity is a prevalent global health issue affecting approximately half of the world's population. Extensive scientific research highlights the urgent need for effective obesity management to mitigate health risks and prevent complications. While bariatric surgery has proven to be highly effective, providing substantial short-term and long-term weight loss and resolution of obesity-related comorbidities, it is important to recognize its limitations and associated risks. Given the global obesity epidemic and the limitations of surgical interventions, there is high demand for effective and safe anti-obesity medications (AOMs). In Korea, the Korean Society for the Study of Obesity strongly advocates for the use of pharmacotherapy in Korean adults with a body mass index of 25 kg/m2 or higher who have not achieved weight reduction through non-pharmacological treatments. Currently, five AOMs have been approved for long-term weight management: orlistat, naltrexone/bupropion, phentermine/topiramate, liraglutide, and semaglutide. Tirzepatide is awaiting approval, and compounds such as CagriSema (Novo Nordisk) and oral semaglutide are currently undergoing rigorous evaluation in phase 3 clinical trials. Furthermore, other promising drugs, including orforglipron, BI 456906, and retartrutide, are progressing to phase 3 studies, expanding the therapeutic options for obesity management. In personalized patient care, physicians play a crucial role in accurately identifying individuals who genuinely require pharmacotherapy and selecting appropriate AOMs based on individual patient characteristics. By integrating evidence-based interventions and considering the unique needs of patients, healthcare professionals significantly contribute to the success of obesity management strategies.

Low eating self-efficacy is associated with unfavorable eating behavior tendencies among individuals with overweight and obesity

Success in long-term weight management depends partly on psychological and behavioral aspects. Understanding the links between psychological factors and eating behavior tendencies is needed to develop more effective weight management methods. This population-based cross-sectional study examined whether eating self-efficacy (ESE) is associated with cognitive restraint (CR), uncontrolled eating (UE), emotional eating (EE), and binge eating (BE). The hypothesis was that individuals with low ESE have more unfavorable eating behavior tendencies than individuals with high ESE. Participants were classified as low ESE and high ESE by the Weight-Related Self-Efficacy questionnaire (WEL) median cut-off point. Eating behavior tendencies were assessed with Three Factor Eating Questionnaire R-18 and Binge Eating Scale, and additionally, by the number of difficulties in weight management. The difficulties were low CR, high UE, high EE, and moderate or severe BE. Five hundred and thirty-two volunteers with overweight and obesity were included in the study. Participants with low ESE had lower CR (p < 0.03) and higher UE, EE, and BE (p < 0.001) than participants with high ESE. Thirty-nine percent of men with low ESE had at least two difficulties in successful weight control while this percentage was only 8% in men with high ESE. In women, the corresponding figures were 56% and 10%. The risk of low ESE was increased by high UE [OR 5.37 (95% CI 1.99–14.51)], high EE [OR 6.05 (95% CI 2.07–17.66)], or moderate or severe BE [OR 12.31 (95% CI 1.52–99.84)] in men, and by low CR [OR 5.19 (95% CI 2.22–12.18)], high UE [OR 7.20 (95% CI 2.41–19.22)], or high EE [OR 23.66 (95% CI 4.79–116.77)] in women. Low ESE was associated with unfavorable eating behavior tendencies and multiple concomitant difficulties in successful weight loss promotion. These eating behavior tendencies should be considered when counseling patients with overweight and obesity.