Weight Loss Strategies Research Articles

Usage, knowledge and perception of the ketogenic diet and associated factors in Saudi adults: A cross-sectional study.

The ketogenic diet (KD) is a popular weight management method. However, knowledge, perceptions, and use of KD have not been studied in the Saudi population. This cross-sectional study aims to assess the knowledge, perceptions, and use of the KD in Saudi Arabia, to compare medical and nonmedical students in their awareness of KD, and to determine factors associated with knowledge and perception of KD. A total of 1071 Saudis aged ≥ 18 years old were included. Participants were excluded if they were younger than 18, non-Saudi, pregnant, breastfeeding, had chronic illnesses, were using any medication, or were diagnosed with psychiatric conditions. Knowledge, perception, and use of KD were collected between 2021 and 2022 in Saudi Arabia using a prevalidated tool and its scoring protocol; higher scores indicated higher level of knowledge or perception. Among Saudi adults, 24% (n = 253) and 55% of them (n = 138/253) followed the KD for 1 month or less, respectively. The KD knowledge score was mean ± SD: 7.95 ± 3.97 and half of the participants (49.5%) had a low knowledge level. Students had a significantly lower knowledge score (mean ± SD: 7.69 ± 3.85) compared to nonstudents (mean ± SD: 8.68 ± 4.19). Students in medical majors had a higher knowledge score compared to nonmedical major students (P < .001). The KD perception score was mean ± SD: 28.74 ± 4.83 and 76% of the participants had moderate perception level. Males had a significantly higher perception score compared to females (P < .001). Students in medical majors had a lower perception score compared to nonmedical major students. Age and body mass index had a significantly weak positive correlation with knowledge and perception scores. Half of the sample had low knowledge and moderate level of perception about KD. Students with medical majors had higher knowledge but lower perception scores compared to nonmedical majors. Dieticians may measure the knowledge and perception of the KD diet in outpatient clinics to lose weight. Educational institutions may increase students' knowledge and perception of the KD in all majors. Future experimental studies examining the efficacy of the KD are needed to provide recommendations of the KD as a strategy for weight loss.

A GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settings

Obesity is a major public health crisis. Multi-specific peptides have emerged as promising therapeutic strategies for clinical weight loss. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are endogenous incretins that regulate weight through their receptors (R). AMG 133 (maridebart cafraglutide) is a bispecific molecule engineered by conjugating a fully human monoclonal anti-human GIPR antagonist antibody to two GLP-1 analogue agonist peptides using amino acid linkers. Here, we confirm the GIPR antagonist and GLP-1R agonist activities in cell-based systems and report the ability of AMG 133 to reduce body weight and improve metabolic markers in male obese mice and cynomolgus monkeys. In a phase 1, randomized, double-blind, placebo-controlled clinical study in participants with obesity (NCT04478708), AMG 133 had an acceptable safety and tolerability profile along with pronounced dose-dependent weight loss. In the multiple ascending dose cohorts, weight loss was maintained for up to 150 days after the last dose. These findings support continued clinical evaluation of AMG 133.

Dietary restraint and emotional eating among elite/international combat sport athletes

ABSTRACT In one-on-one combat sport, weight classifications are enforced to promote fair fights and minimise injury risk. Most combat sport athletes try to fight at weight much lower than their natural weight necessitating use of weight loss strategies including restrained eating prior to competition. Previous research indicates that individuals self-reporting as high in dietary restraint also self-report a higher desire to emotionally eat, which if acted upon would compromise weight management goals. This mixed-methods exploratory study examined associations between dietary restraint and emotional eating among elite/international combat sport athletes. Nineteen elite/international competitors in Brazilian Jiu Jitsu and Mixed Martial Arts completed the emotional eating scale, a revised restraint scale, and a rapid weight loss questionnaire. A subsample of six participants then completed individual interviews to explore emotional eating, particularly during the lead-up to and post-competition. Quantitative findings via non-parametric tests found high scores in restrained eating associated with a greater urge to emotionally eat. Qualitative findings via content analysis of interview data identified three themes that helped understand this association, “emotions eliciting an urge to eat”, “outcomes of emotional eating”, and “resisting emotional eating”. Participants described a cycle of restrained eating pre-competition followed by an increased tendency toward emotional eating post-competition, with the extent of emotional eating influenced by the degree of restrained eating required and competition outcomes.

Association of largest meal timing and eating frequency with body mass index and obesity

Background and AimsThe circadian pattern of eating behaviors has garnered increasing interest as a strategy for obesity prevention and weight loss. It is believed that the benefits stem from aligning food intake with the body's natural daily rhythms. However, the existing body of evidence is limited in scale and scope and there has been insufficient evaluation of temporal eating behaviors, such as the specific time of day in which the highest calorie consumption occurs, meal frequency, and distribution. This research aims to explore the association between the timing of the largest meal of the day and eating frequency with Body Mass Index (BMI) and obesity. MethodsParticipants (n=2 050, 18-65y) were part of an exploratory cross-sectional and population-based research, with data collection in a virtual environment. Linear regression analyses and restricted cubic splines evaluated differences in BMI associated with independent eating variables [timing of the largest meal, number of meals/day (as continuous and categorical: ≤3 or >3/day), and each largest meal of the day (breakfast/lunch/dinner)]. Logistic regression models were fitted to assess Odds Ratios (OR) and 95% Confidence Intervals (CI) of obesity associated with the same independent variables. ResultsOur main findings were that the timing of the largest meal and reporting dinner as the largest meal were associated with higher values of BMI (respectively, 0.07Kg/m2 and 0.85Kg/m2,) and increased odds of obesity [respectively OR(95%CI):1.04(1.01,1.08), and OR(95%CI):1.67(1.18,2.38)]. Those who realized more than 3 meals/day presented lower values of BMI (-0.14Kg/m2) and 32% lower odds of having obesity [OR(95%CI):0.68(0.52,0.89)]. Reporting lunch as the largest meal also protected against obesity [OR(95%CI):0.71(0.54,0.93)]. These associations were statistically significant and independent of sex, age, marital status, education level, diet quality, sleep duration, and weekly frequency of physical exercise. ConclusionHaving the largest meal earlier in the day, concentrating the majority of caloric intake during lunch, and consuming more than three meals a day, may present a promising intervention for preventing and treating obesity/overweight.

Exploring the Intricate Interplay Between Obesity and Atrial Fibrillation: Mechanisms, Management, and Clinical Implications.

Atrial fibrillation (AF) stands as a prevalent and escalating cardiac arrhythmia in the United States, with obesity emerging as a prominent modifiable risk factor. This article explores the intricate relationship between obesity and AF, delving into the multifaceted pathophysiological mechanisms linking the 2 conditions. Various factors, such as autonomic dysfunction, left atrial stretch, inflammation, and hormonal imbalances, contribute to the initiation and perpetuation of AF in obese individuals. The Atrial Fibrillation Better Care pathway, emphasizing lifestyle modifications and weight loss strategies, emerges as a practical guideline for managing AF in obesity. This comprehensive review underscores the critical role of obesity as a significant modifiable risk factor for AF, urging a proactive approach to its management. Implementing the Atrial Fibrillation Better Care approach, focusing on encouraging physical activity, promoting healthy dietary habits, and raising awareness about the risks associated with obesity prove essential in preventing and mitigating the burden of AF in the obese population.

Nutrition knowledge, weight loss practices, and supplement use in senior competition climbers.

Sport climbing has gained increased scientific attention, including studies investigating the dietary habits and nutritional requirements of climbers; however, significant gaps in the literature remain. An assessment of nutritional knowledge, weight loss for competition, and supplement use has not been previously reported in senior competition climbing athletes. Fifty climbers (26 male, 24 female; BMI 21.6 ± 1.9; 23.7 ± 5.2 years) participated in the study. Participants answered a 72-item questionnaire, comprised of demographic data and three main sections to assess general and sports nutrition knowledge, weight loss strategies, and supplement use. The mean nutrition knowledge score was 'average', with considerable individual variation (53.5 ± 11.1 %). There were no significant sex differences in the general (GNK) or sport (SNK) nutrition knowledge scores, or effect of age. Significantly higher knowledge was demonstrated by national vs. international athletes for the GNK scores (11.09 ± 1.58 vs. 9.58 ± 1.75; p = 0.028). Participants scored well in questions concerning protein, carbohydrates, alcohol, and supplements, and conversely, performed poorly in hydration and micronutrient related questions. Less than one-fifth of respondents had access to a dietitian. Forty-six percent of males and 38% of female climbers reported intentional weight loss for competition on at least one occasion. Of those, ~76% reported utilizing concerning practices, including methods that conform with disordered eating and/or eating disorders, dehydration, vomiting, and misuse of laxatives. Approximately 65% of athletes reported using at least one nutritional supplement in the previous 6 months, with 44% reporting multiple supplement use. There was no significant difference in supplement use between sexes or competition level. Due to the established importance of nutritional intake on athlete health and performance, educational support should be employed to improve knowledge in climbers and address shortcomings. Moreover, intentional weight loss for climbing competition is common, with most athletes achieving ~3-8% body weight loss over ≥2 weeks. It is crucial that professionals working with competitive climbers are vigilant in identifying athletes at risk of concerning weight management and establish referral pathways to the appropriate specialist services. High quality intervention trials to assess the efficacy of ergogenic aids in climbing remains inadequate.

Obesity-Resistant Mice on a High-Fat Diet Display a Distinct Phenotype Linked to Enhanced Lipid Metabolism.

Individually, metabolic variations can significantly influence predisposition to obesity in the form of the obesity-prone (super-responders) and obesity-resistant (non-responders) phenotypes in response to modern calorie-dense diets. In this study, C57BL/6J mice (n = 76) were randomly assigned to either a low-fat diet (LFD) or a high-fat diet (HFD) for 6 weeks, followed by selection of the normally obese (HFD), non-responders (NR), super-responders (SR), or super-responders switched back to the low-fat diet (SR-LFD) for an additional 8 weeks. SR mice showed the highest gains in body weight, lean and fat body mass, and total and free water, in part due to increased feed efficiency, despite having a respiratory exchange ratio (RER) similar to that of NR mice. A switch to the LFD was sufficient to revert most of the observed physiological changes in the SR-LFD mice; however, voluntary physical activity and exercise capacity did not return to the basal level. NR mice showed the highest food intake, lowest feed efficiency, increased oxygen consumption during the light (rest) cycle, increased physical activity during the dark (active) cycle, and increased heat production during both cycles. These variations were observed in the absence of changes in food intake and fecal parameters; however, NR fecal lipid content was lower, and the NR fecal microbiome profile was characterized by reduced abundance of Actinobacteria. Taken together, our findings suggest that NR mice showed an increased ability to metabolize excessive dietary fats in skeletal muscle at the expense of reduced exercise capacity that persisted for the duration of the study. These findings underscore the need for further comprehensive investigations into the mechanisms of obesity resistance, as they hold potential implications for weight-loss strategies in human subjects.

Weight loss strategies in the post transplanted: connected health services and group intervention

Weight loss strategies in the post transplanted: connected health services and group intervention

Lifestyle Behavioral Strategies for Weight Loss in Older Adults

Lifestyle Behavioral Strategies for Weight Loss in Older Adults

Body Mass Management Practices of Olympic Weightlifting Athletes.

This study explored the body mass (BM) management practices among competitive male and female Olympic weightlifting athletes, hypothesizing that athletes compete in lighter weight categories than their habitual training weight (i.e.,making weight). Utilizing a validated, anonymous survey, data were collected from 149 Olympic weightlifting athletes (>18years; female = 94). The survey comprised five sections: demographics, training/competition history, weight history, source of influence, and BM management practices. The prevalence, magnitude, and methods employed for BM management were analyzed with subgroup analysis using one-way analysis of variance. Post hoc testing including Spearman's rho and chi-square analysis was completed when a significant effect was found. Three quarters (76%) of athletes acknowledged using chronic weight loss and/or acute weight loss strategies to make weight. Usual BM loss (2%-3%) in the week before competition was within recommended guidelines. Gradual dieting, fluid restriction, and low food weight, high-calorie options were the most commonly used BM management strategies. Female athletes were more likely to use gradual dieting (p = .043; r = .104) and were less likely to increase their exercise (p = .046; r = -.105) and utilize fasting (p = .038; r = .05) compared with their male counterparts. Women further identified dietitians/nutritionists (p = .006; r = .022) as a highly influential source of information. This research offers new insights into the BM management practices of Olympic weightlifting athletes, identifying that the majority of athletes compete at a BM lighter than their habitual training weight, achieved using a range of chronic weight loss and acute weight loss strategies.

A Comparative Analysis of Different Fat Loss Methods: Carb Cycling, Intermittent Fasting, and Ketogenic Diet

The evolving landscape of weight loss research emphasizes tailored approaches for success. This paper aims to provide comprehensive insights into these methods’ mechanisms, advantages, and limitations, equipping individuals with knowledge for informed weight management decisions. This paper explores three distinct weight loss strategies: carbohydrate cycling, the ketogenic diet, and intermittent fasting. Each method offers unique approaches to address the global concern of obesity. Carbohydrate cycling involves alternating between low and high carbohydrate intake days. The ketogenic diet shifts the body’s energy source to fats, potentially enabling rapid weight reduction but raising long-term safety concerns. Intermittent fasting alternates fasting and eating windows, with various patterns. The effects, limitations, and target populations of each strategy are analyzed, considering exercise habits, dietary preferences, and medical conditions. Personalized strategies are essential due to individual diversity. While these methods have clear benefits, no one-size-fits-all solution exists. As these strategies continue to evolve, their potential impacts extend beyond weight loss to broader aspects of health and well-being.

Impact on weight loss and body composition of a food education intervention associated with Liraglutide treatment to address obesity

Introduction: clinical practice guidelines recommend considering pharmacological treatment of obesity only as a complement to lifestyle modification. Drugs alone are usually ineffective in the long term after discontinuation, so pharmacological weight loss strategies should always be accompanied by lifestyle modifications. Objective: to analyze the changes in weight, body mass index and body composition by means of electrical bioimpedance after a 32-week treatment with liraglutide in patients with obesity, associated or not with a food education program. Materials and methods: the study involved 68 patients who were randomly divided into 2 groups. One group received treatment with liraglutide 3.0 mg/day along with individual dietary education, and the other group was treated with liraglutide 3.0 mg/day and standard medical follow-up for 32 weeks. The data collected were weight (kg), height (m) (Seca® brand), body mass index (kg/m2) and body composition using multifrequency bioimpedance (SECA 112® brand). The variables were analyzed at the beginning and at the end of the treatment. Results: after 32 weeks of treatment, both study groups lost weight significantly. The group treated with liraglutide and individual dietary education had a reduction of 8.77 kg (9.08 %) (p < 0.001) and the group treated with liraglutide without education had a reduction of 3.55 kg (3.45 %) (p < 0.001). The BMI of the participants treated with liraglutide and education decreased by -4,04 kg/m2 (10.35 %) (p < 0.001) and in the group without education it decreased by -3.22 kg/m2 (8.30 %) (p = 0.003). In the educated group, fat mass decreased by -7.65 kg (15.89 %) (p < 0.001), although skeletal muscle mass also decreased by -1.62 kg (6.8 %) (p < 0.001). In those treated with liraglutide without education, a reduction in fat mass and skeletal muscle mass was also observed - fat mass by -4.72 kg (9.43 %) (p < 0.001) and skeletal muscle mass by -0.17 kg (0.70 %) (p < 0.001). Differences were also observed between groups, observing a greater reduction in weight, BMI, fat mass and skeletal muscle mass in the group with liraglutide and education compared to the group without education, although these differences were not statistically significant. Conclusions: dietary education associated with liraglutide treatment may contribute to increasing weight and fat mass losses. However, it was also associated with an unwanted loss of skeletal muscle mass, probably related to the greater intensity of weight loss, which will have to be reversed in future therapeutic approaches. Habit modification through multidisciplinary treatment, including nutritional education, combined strength and resistance exercise, and cognitive-behavioral therapy, could be an effective way to treat obesity and maintain weight, body composition, and adherence to a lifestyle.

Dynamical alterations of brain function and gut microbiome in weight loss.

Intermittent energy restriction (IER) is an effective weight loss strategy. However, little is known about the dynamic effects of IER on the brain-gut-microbiome axis. In this study, a total of 25 obese individuals successfully lost weight after a 2-month IER intervention. FMRI was used to determine the activity of brain regions. Metagenomic sequencing was performed to identify differentially abundant gut microbes and pathways in from fecal samples. Our results showed that IER longitudinally reduced the activity of obese-related brain regions at different timepoints, including the inferior frontal orbital gyrus in the cognitive control circuit, the putamen in the emotion and learning circuit, and the anterior cingulate cortex in the sensory circuit. IER longitudinally reduced E. coli abundance across multiple timepoints while elevating the abundance of obesity-related Faecalibacterium prausnitzii, Parabacteroides distasonis, and Bacterokles uniformis. Correlation analysis revealed longitudinally correlations between gut bacteria abundance alterations and brain activity changes. There was dynamical alteration of BGM axis (the communication of E. coli with specific brain regions) during the weight loss under the IER.

Effectiveness of Time-Restricted Eating with Caloric Restriction vs. Caloric Restriction for Weight Loss and Health: Meta-Analysis

Time-restricted eating (TRE) is an increasingly popular dietary strategy for weight loss. Recent studies suggest that combining TRE with caloric restriction (CR) may have more favorable effects on both physical and biochemical aspects when compared with CR alone. Therefore, we performed a meta-analysis to compare the effects of TRE with CR vs. CR alone on anthropometric and biochemical measures in overweight or obese adults. We reviewed articles from PubMed, Web of science, EMBASE, and the Cochrane Library published before 25 May 2023. The meta-analysis incorporated data from seven randomized controlled trials of nine interventions, with a total of 231 participants in the TRE with CR group and 227 participants in the CR-only group. Data were analyzed using RewMan version 5.4.1. All results in our meta-analysis were described as mean difference (MD) with 95% confidence interval (Cl). Results showed that TRE with CR compared to CR alone resulted in significantly greater reductions in body weight (MD: −2.11 kg, 95% CI: −2.68 kg to −1.54 kg, p = &lt; 0.00001, I2 = 42%), body fat mass (MD: −0.75 kg, 95% CI: −1.35 kg to −0.16 kg, p = 0.01; I2 = 0%), and waist circumference (MD: −1.27 cm, 95% CI: −2.36 cm to −0.19 cm, p = 0.02, I2 = 0%), while no additional impact of TRE in combination with CR in comparison to CR on serum biochemical parameters were found. Our results suggest that the improvement in biochemical parameters are mainly caused by CR, while improvements in anthropometric parameters are further enhanced by TRE.

Eating patterns contribute to shaping the gut microbiota in the mucosal simulator of the human intestinal microbial ecosystem.

Eating patterns, i.e. meal frequency and circadian timing of meals, are often modified in weight loss and metabolic healing strategies. However, in-depth research into the effects on the gut microbiome remains scarce, particularly across various colon regions and niches. We identified eating patterns to contribute in shaping the in vitro gut biomass production, metabolism, and microbial community compositions by subjecting four faecal microbiomes to a pattern that is standardized for a dynamic gut model (feeding at 09, 17, and 01 h), a typical Western (breakfast, lunch, and dinner at 09, 13, and 19 h, respectively), and a time-restricted pattern (single meal at 09 h). While eating patterns moderately affected the microbiome (2.4% and 1.8% significant variation in proportional and quantitative microbial compositions, respectively), significant changes were noted in the time-restricted pattern, including increased Bacteroides, Butyricicoccus, Dialister, and Faecalibacterium abundances. Sampling every 4 h revealed no significant circadian fluctuations in biomass production, microbial community compositions, or functionality. Longer fasting times favoured the growth of slower-growing species, such as Akkermansia, Dialister, and Parasutterella over faster-growers, such as Pseudomonas and Stenotrophomonas. Our findings illustrate the importance of recording and considering eating patterns as a gut microbiome determinant in in vivo and in vitro dietary intervention studies.

Awareness About the Benefits of Post-bariatric Surgery in Diabetic Patients in Makkah Almukarramah, Saudi Arabia.

To measure awareness about the benefits of post-bariatric surgery, which is a shortening of the gut in order to lose weight in diabetic patients in the Makkah region, Saudi Arabia. A cross-sectional survey was conducted among diabetic patients aged 18-65 from February to July 2023. An online questionnaire via Google Forms was distributed and used to assess the participants' awareness of the benefits of post-bariatric surgery for diabetic patients. Overall, 388 participants (56.40% female, 43.60% male) were surveyed. Most participants (91.5%) showed awareness of gastric sleeve surgery, while a significant proportion (85.8%) recognized obesity as a disease. A majority of participants (80.90%) showed awareness of the association between obesity, diabetes, and high blood pressure. However, only 46.10% of participants showed awareness of eligibility criteria associated with bariatric surgery. The majority recognized the effectiveness of bariatric surgery for weight loss but did not consider it the first choice, emphasizing a preference for non-surgical weight loss strategies. Participants demonstrated good knowledge about obesity and its implications for health. They also demonstrated good knowledge about bariatric surgery as an effective weight reduction method but expressed a preference for non-surgical methods, which reflects their awareness of the complications of bariatric surgery. However, the results showed a lack of awareness of postoperative indications and lifestyle changes, thus highlighting the need for comprehensive patient education and counseling.

Application of various weight loss strategies in sambo athletes

Application of various weight loss strategies in sambo athletes

Advances in Anti-obesity Pharmacotherapy: Current Treatments, Emerging Therapies, and Challenges.

Obesity is a major public health concern linked to health risks such as hypertension, hyperlipidemia, type 2 diabetes mellitus (T2DM), stroke, metabolic syndrome, asthma, and cancer. It is among the leading causes of morbidity and mortality worldwide caused by an unhealthy diet and lack of physical activity, but genetic or hormonal factors may also contribute. Over a third of adults in the United States are obese. Pharmacological agents have been designed to reduce weight gain caused by excessive calorie intake and low physical activity. They work by inhibiting the absorption of dietary fat or stimulating the secretion of satiety hormones. These drugs include lipase inhibitors and glucagon-like peptide1 (GLP-1) receptor agonists. However, the current weight-loss strategies do not effectively treat genetic-related diseases, such as generalized lipodystrophy, Bardet-Biedl syndrome, and proopiomelanocortin (POMC) deficiency. Emerging therapies for these gene mutations have been developed targeting leptin and melanocortin-4 receptors (MC4Rs), restoring the normal function of leptin or melanocortin-4 receptors regulating energy balance and appetite. Leptin analogs and MC4R agonists are novel therapies that target genetic or hormonal causes of obesity. This article provides a comprehensive review of anti-obesity medications (AOMs). In this review, we discuss the clinical trials, efficacy, United States FDA-approved indication, contraindications, and serious side effects of different classes of drugs, including lipase inhibitors, GLP-1 agonists, leptin analogs, and MC4R agonists.

FRI017 Precision-engineered Activin And GDF Ligand Trap HS235: A Novel Lean Mass-preserving Treatment for Obesity

Abstract Disclosure: G. Schang: Employee; Self; 35Pharma Inc. M. Poujol de Molliens: Employee; Self; 35Pharma Inc. E. Brûlé: Employee; Self; 35Pharma Inc. C. Chauvet: Employee; Self; 35Pharma Inc. J. Denis: Employee; Self; 35Pharma Inc. A. Sours: Employee; Self; 35Pharma Inc. V. Ganesh: Employee; Self; 35Pharma Inc. G. Tremblay: Employee; Self; 35Pharma Inc. J. Schoelermann: Employee; Self; 35Pharma Inc. M. O'Connor-McCourt: Employee; Self; 35Pharma Inc. Introduction: Novel anti-obesity medications including incretin mimetics have revolutionized the pharmacotherapy of obesity and type 2 diabetes, leading to unprecedented weight loss and clinically meaningful improvement of glucose metabolism and cardiometabolic health. However, this loss of fat mass is accompanied by undesirable loss of lean body mass (LBM) which can account for 15 - 40% of overall weight loss. Loss of LBM by incretin-based therapies negatively impacts resting metabolic rate, leading to a weight loss plateau and often unsustainable results. The preservation, or even increase, of LBM is therefore a desirable treatment goal for obesity pharmacotherapy and improvement of overall health. Activins and growth differentiation factors (GDFs), which are members of the TGF-beta superfamily, are validated targets controlling body composition and metabolism. Specifically, blockade of activins and GDFs has anabolic effects in metabolically active tissues such as skeletal muscle and brown adipose tissue, while reducing white adipose tissue mass. Therefore, specific and selective blockade of activins and GDFs represents a novel anti-obesity treatment strategy which can act orthogonally to current anti-obesity medications. Aims and objectives: HS235 is an activin receptor ectodomain-based (ActR) Fc-fusion protein that has been rationally designed to attain optimal inhibition of ligands controlling body composition in obesity. Methods: A structure-assisted rational molecular engineering approach coupled with cell-based potency screening was employed to design HS235. In vivo target engagement and pharmacodynamic response to HS235 were assessed in mice by quantifying metabolic biomarkers including muscle hypertrophy, muscle and fat gene expression, as well as plasma metabolites. To further validate the anti-obesogenic potential of HS235, diet-induced obese (DIO) mice were injected with HS235, an incretin mimetic, or a combination of both. Fat mass, LBM, glucose metabolism, exercise tolerance, and biomarker readouts were assessed at the end of study. Results: In cell-based assays, HS235 potently and selectively neutralized activins and GDFs implicated in body composition. This translated to complete in vivo target engagement and pharmacodynamic response. In a DIO mouse model, both HS235 and the incretin mimetic significantly improved metabolic parameters and decreased fat mass, but only HS235 increased LBM, while incretin-based treatment led to LBM loss. Importantly, the addition of HS235 to the incretin mimetic prevented this loss of LBM. Conclusion: Potent and selective inhibition of activins and GDFs by HS235 represents a novel LBM preserving weight loss strategy. Collectively, these data support the development of HS235 as a novel anti-obesity agent that may also complement currently approved incretin-based medications. Presentation: Friday, June 16, 2023

Dietary treatment postpartum in women with obesity reduces weight and prevents weight gain: a randomised controlled trial

BackgroundWomen with pre-pregnancy obesity have an increased risk of retaining or gaining weight postpartum and may benefit from weight loss treatment. However, evidence is lacking for weight loss strategies in women with BMIs in the higher obesity classes. A dietary treatment for postpartum weight loss resulted in a 10% weight reduction in lactating women with a mean BMI of 30 kg/m2. We aimed to examine the effects of this dietary treatment on changes in weight, markers of lipid and glucose metabolism, waist and hip circumference and postpartum weight retention (PPWR) in postpartum women with higher BMIs than tested previously.MethodsAt baseline, approximately 8 weeks postpartum, 29 women with a mean (SD) BMI = 40.0 (5.2) kg/m2 were randomised to a 12-week dietary treatment (n 14) or to a control treatment (n 15). Measurements were made at baseline and after 3 and 12 months. Data was analysed using mixed model.ResultsThe mean weight change in the diet group was -2.3 (3.1) kg compared to 1.7 (3.1) kg in the control group after 3 months (P = 0.003) and -4.2 (5.6) kg compared to 4.8 (11.8) kg in the control group after 12 months (P = 0.02). The dietary treatment led to reduced waist circumference (P < 0.04) and PPWR (P < 0.01) compared to the control treatment at both time points. The treatment lowered fasting blood glucose at 12 months (P = 0.007) as the only effect on markers of lipid and glucose metabolism.ConclusionThe dietary treatment postpartum reduced weight and prevented weight retention or weight gain in women with obesity.Trial registrationThe trial was retrospectively registered at ClinicalTrials.gov (NCT03579667) 06/07/2018.Graphical In a randomised, controlled trial, 29 postpartum women with obesity were allocated to a dietary treatment or a control treatment. The dietary treatment reduced weight and prevented postpartum weight retention or weight gain after 12 months.Reference: Adapted from “Randomized, Placebo-Controlled, Parallel Study Design (2 Arms, Graphical)”, by BioRender.com (2022). Retrieved from https://app.biorender.com/biorender-templates.