Reduced Body Mass Research Articles

The use of copper sulfate to control mussel (Mytella strigata) invasive events in the Penaeus vannamei shrimp farming: Doses, effects, and depuration

The global production of Pacific white shrimp Penaeus vannamei (Boone, 1931) has increased annually with advances in farming techniques. However, like any open system, it is subject to economic losses from invasive organisms, predators, and diseases. The lagoon mussel Mytella strigata, which massively invades culture ponds, reduces the primary productivity necessary for raising juvenile shrimp and is typically treated with copper sulfate pentahydrate (CuSO4.5H2O) as a molluscicide. In the search for copper sulfate doses that are effective for controlling M. strigata and cultivating P. vannamei, the mean lethal concentration for mussels (LC50; 0.57 mg CuSO4.5H2O L−1) and shrimp (LC50; 2.91 mg CuSO4.5H2O L−1) was estimated. Subsequently, the acute effect of CuSO4.5H2O on biometry and endogenous energy reserves by exposing shrimp to a dose of 1.20 mg CuSO4.5H2O L−1, and the amount of metal accumulated and detoxified from the soft tissue and exoskeleton (lethal for mussels and sublethal for shrimp) was evaluated for 12 d, followed by a detoxification period for 5 d. A significant reduction in body mass in CuSO4.5H2O-exposed shrimp was observed. Copper content was higher in the exoskeleton of CuSO4-exposed shrimp (146.3 ± 26.2 μg Cu g−1), decreasing significantly with depuration (97.9 ± 26.0 μg Cu g−1). In the soft tissue, 53.3 ± 9.8 μg Cu g−1 was accumulated, decreasing to 6.2 ± 1.3 μg Cu g−1, showing a higher percentage of detoxification (88.3 %) compared to the exoskeleton (48.5 %). Protein, carbohydrate, and lipid concentrations were not altered during copper exposure and depuration. The results suggest that sublethal exposure to CuSO4.5H2O does not affect survival, and although shrimp biomass decreased (19 % compared to control), there was no effect on their biochemical composition. Our research recommends using 1.2 mg L−1 of CuSO4.5H2O to control specific events of mussel invasion, which could be included within protocols of low environmental impact and cost.

Impact of daily fasting duration on body composition and cardiometabolic risk factors during a time-restricted eating protocol: a randomized controlled trial

BackgroundTime-restricted eating (TRE) is a dietary regimen that limits food intake for at least 12 h daily. Unlike other fasting protocols, TRE does not dictate what or how much to eat but rather focuses on the timing of meals. This approach has been previously demonstrated to improve body composition in individuals with obesity or metabolic impairments. However, its impact on body composition and cardiometabolic factors in healthy individuals remains unclear. Furthermore, the optimal fasting duration is still debated. Thus, we aimed to compare the effects of 8 weeks of different fasting durations on body composition and biochemical parameters in metabolically healthy, non-trained individuals using a parallel randomized controlled trial.MethodsForty-one volunteers were randomly assigned to one of the four experimental groups: TRE 16:8 (16 h of fasting,8 h of eating), TRE 14:10 (14 h of fasting,10 h of eating), TRE 12:12 (12 h of fasting,12 h of eating) or a normal diet group (ND; no dietary restriction). Participants underwent body composition measurements and blood tests for lipid profiles (i.e., total cholesterol, LDL, HDL, and triglycerides), fasting glucose, leptin, and anabolic hormones (i.e., insulin and testosterone) levels. Data were analyzed using both intention-to-treat (ITT) and per-protocol (PP) analysis to account for compliance. A two-way ANOVA for repeated measures was employed to assess interactions between time and group.ResultsIn the ITT analysis, TRE 16:8 reduced body mass (-2.46%, p = 0.003) and absolute fat mass (-8.65%, p = 0.001) with no changes in lean soft tissue and in calorie intake. These results were consistent with the PP analysis which included 8 participants in TRE 16:8, 5 in TRE 14:10, 9 in TRE 12:12, and the entire ND group. Participants in the TRE 16:8 group spontaneously reduced their total caloric intake, although this reduction was not statistically significant. None of the other measurements significantly changed after 8 weeks.ConclusionsOur results suggest that a 16-hour fasting window, even without caloric restriction, may be a viable strategy for improving body composition in healthy and non-trained individuals, whereas a shorter fasting period may be insufficient to produce significant changes in a healthy population.Trial registrationNCT, NCT04503005. Registered 4 August 2020, https://clinicaltrials.gov/study/NCT04503005.

Synergistic toxicity of cadmium and triadimefon on the microbiota and health of Rana dybowskii tadpoles

The skin and gut microbiota are crucial to amphibians. Triadimefon (TF), a widely used triazole fungicide, controls crop diseases and regulates growth, with uncertain effects on amphibian microbiota. Contamination, typically involving mixed chemicals at low concentrations, including cadmium (Cd) and TF, may detrimentally affect amphibian growth, survival, and microbiota health in both the skin and gut, but few research has examined these consequences. This research examines the impact of Cd and TF on Rana dybowskii tadpoles, focusing on survival, body mass, and microbiome changes over 28 days across four groups: control, Cd, TF, and Cd + TF groups. Results showed significant reductions in survival and body mass in Cd and TF-treated groups, with the combination group being the most affected. Microbiota analysis revealed significant dysbiosis in both gut and skin microbiomes under pollutant stress, with a marked microbiota and a shift in dominant microbial communities. Function prediction analysis based on the microbiome composition highlighted significant differences across various biological pathways, including metabolism, immune system, environmental adaptation, and disease resistance. These alterations suggest that pollutant exposure compromises the tadpoles' ability to maintain homeostasis and resist pathogens. In conclusion, this study reveals the detrimental effects of Cd and TF on the survival, growth, and microbiomes of R. dybowskii tadpoles, indicating significant environmental and health risks.

Effectiveness of glucagon-like peptide-1 receptor agonists for reduction of body mass index and blood glucose control in patients with type 2 diabetes mellitus and obesity: A retrospective cohort study and difference-in-difference analysis

ObjectiveThis study aimed to evaluate the effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1RA) in reducing body mass index (BMI) and blood glucose levels in individuals with type 2 diabetes mellitus...

Effect of Early Postoperative Mobilization on Functional Recovery, Hospital Length of Stay, and Postoperative Complications After Immediate Internal Pudendal Artery Perforator Flap Reconstruction for Irradiated Abdominoperineal Resection Defects: A Prospective, Randomized Controlled Trial.

Patients undergoing perineal defect reconstruction with the internal pudendal artery perforator (IPAP) flap traditionally face 5days of postoperative bed rest (BR) to minimize surgical risks. However, prolonged BR can exacerbate postoperative physiologic changes such as increased fatigue, reduced body mass, and declining lung function, while also leading to complications such as pneumonia, delirium, deep vein thrombosis, and pressure injuries. This study assessed the effectiveness, feasibility, and safety of an adapted early mobilization (EM) program for these patients. This prospective, randomized, controlled clinical study involved 51 patients assigned to adapted EM (n = 25) or BR (n = 26). Whereas EM included core exercises, orthostasis training, gait training, muscle strengthening, and aerobic exercises after surgery, BR followed standard bed rest protocols. The primary outcome was independent ambulation for 3 m on postoperative day 5. The secondary outcomes included 6-min walk test (6MWT) distances on days 5 and 30, hospital length of stay, healing time, postoperative complications, fatigue prevalence, and quality of life. On day 5, EM improved ambulation significantly compared with BR (68.0% vs 38.5%; P = 0.035) and achieved greater 6MWT distances on days 5 (108.78 vs 47.73m; P = 0.041) and 30 (243.8 vs 166.29m; P = 0.018). The EM patients were discharged earlier (66.7% by day 10 vs 33.3% of the BR patients; P = 0.043), with comparable healing times (P = 0.06) and postoperative complication rates (68% vs 80.8%; P = 0.296). Fatigue prevalence and quality of life did not differ significantly between the two groups. Early mobilization after IPAP flap reconstruction is safe and feasible, promoting early ambulation and recovery and facilitating earlier discharge without increasing complications.

The effect of eight weeks of circuit resistance training on Apo-B/A ratio and inflammatory status of sedentary postmenopausal women

Abstract Exercise can be an effective non-pharmacological method to reduce the complications of menopause. This study aimed to investigate the effect of 8 weeks of circuit resistance training (CRT) on the levels of C-reactive protein (CRP), intercellular adhesion molecule 1 (ICAM-1), apolipoprotein A (Apo-A), Apo-B, and their ratio in sedentary postmenopausal women. Thirty postmenopausal women (age 54 ± 3 years, body mass index 27.6 ± 1.97 kg/m2) without any serious diseases and no hormone therapy volunteered to participate in the research. The subjects were randomly divided into two groups: circuit resistance training (n = 15, CRT) and Control (n = 15) groups. Resistance training was performed for 8 weeks, 3 days a week, including 12 stations for the whole body in 3 sets and 8-12 repetitions. The exercises started at 40% of one repetition maximum (1RM) and gradually reached 75% of 1RM in the last week. Blood samples were taken before and 48 hours after the end of both interventions to measure CRP, ICAM-1, Apo-A-I, and Apo-B. To analyse the data, a two-way analysis of variance test was used. The CRT intervention by reducing Apo-B (−8.9% vs −0.1%; change percentage relative to pre-to-post values in each group) and increasing Apo-A1 (+4.7% vs −0.1%) led to a significant increase in the Apo-B/A ratio (−13.0% vs −0.08%) compared to the Control group. In addition, a substantial decrease in the inflammatory levels of CRP (−21.0% vs +6.3%) and ICAM-1 (−22.7% vs +1.6%) was observed after 8 weeks of CRT compared to the Control group. The observed changes were consistent with a reduction in body mass and an improvement in the waist-hip ratio (WHR). The findings indicated that CRT could reduce the complications of menopause by reducing inflammatory markers and improving the lipid profile.

Changes in body mass and urinary biomarkers after a long-lasting combat search and rescue military exercise performed in a tropical region

The study aimed to evaluate body mass changes and urine biomarker responses during a Combat Search and Rescue (CSAR) military exercise performed in a tropical region. Ten urinary biomarkers were analyzed via dipstick urinalysis to assess the physiological strain and the potential health risks associated with this exercise. Body mass and urine samples were obtained from 151 male cadets ([21.3 ​± ​1.6] year-old; height [177.2 ​± ​4.1] ​cm) before and after completing the efforts of a CSAR exercise that lasted approximately 10 ​hour (h). Body mass significantly decreased (p ​< ​0.05) by more than 3% immediately post-exercise (from [75.0 ​± ​9.85] kg to [72.6 ​± ​9.6] ​kg), returning to pre-exercise levels within 14 and 38 ​h after the complen. Interestingly, urine specific gravity (USG) paralleled the changes in body mass and exhibited a significant increase immediately after the exercise. Similar patterns of significant alterations were observed in urine acidity, ketonuria, bilirubinuria, and hematuria, mirroring the time course of changes in USG. The other evaluated urine variables did not show significant changes. The reduction in body mass was significantly correlated with changes in USG, ketonuria, bilirubinuria and proteinuria after the military exercise. In summary, cadets engaged in the CSAR military exercise experienced physiologically meaningful dehydration and exhibited indirect markers of cell damage immediately after the exercise. However, these changes were spontaneously resolved within 14 ​h post-task. Monitoring selected non-invasive biomarkers could aid in managing performance and health risks during arduous military training.

Three and Twelve Month Body Mass Outcomes After Attendance at a Community-Based Weight Management Intervention in the North West of England

Background: Research suggests that commercial weight management services are efficacious in helping people manage their body mass, but they typically only include education and advice on physical activity. The objective of this analysis was to assess 3- and 12-month body mass after attendance at a community-based weight management programme delivered by a commercial slimming group, which included the provision of tailored physical activity sessions by a local leisure trust between January 2009 and November 2014. Methods: After institutional ethical approval and participants giving informed consent, a retrospective analysis of a 12-week multi-component intervention, tier 2 community weight management service for adults in Wigan, North West England, United Kingdom, was undertaken. Participants’ (n = 8514) mean ± SD age was 47.4 ± 14.3 years and starting body mass was 86.7 ± 14.3 kg. The main outcome measure was body mass (kg) at 0 months (baseline), 3 months (immediately post intervention) and 12 months. Significant differences in body mass were ascertained if p &lt; 0.05 using repeated measures ANOVA with Bonferroni post hoc test, with effect sizes calculated using partial eta squared. To confirm and account for missing data, the Last Observation Carried Forward (LOCF) approach was used. Results: Repeated measures ANOVA showed a significant effect of time (p &lt; 0.01, ηp2 = 0.36). Post hoc tests revealed there was a significant reduction in body mass from baseline to 3 months (86.7 ± 14.3 kg vs. 81.2 ± 13.6 kg) and baseline to 12 months (79.7 ± 14.0 kg). The difference between 3 months and 12 months was also significant. LOCF confirmed a significant effect of time (p &lt; 0.01, ηp2 = 0.42), with all previously highlighted significant differences remaining. Conclusions: Significant reductions in body mass were reported at 3 and 12 months, providing evidence for the efficacy of the community weight management programme that included tailored physical activity opportunities for participants. Whilst comparisons to a resting control group cannot be made, partnerships between commercial slimming groups and local leisure providers should be encouraged and explored nationally.

Impact of addressing modifiable risk factors on the 10-year risk of cardiovascular disease in individuals with familial hypercholesterolemia: a causal analysis utilising UK biobank

Abstract Background Familial hypercholesterolemia (FH) is a prevalent autosomal dominant disorder characterised by elevated low-density lipoprotein cholesterol (LDL-C) levels from birth. These elevated LDL-C levels significantly amplify the lifetime risk of cardiovascular disease (CVD). While the impact of early and effective initiation of lipid-lowering medication (LLM) on CVD risk is well documented in genetically confirmed FH, the additional impact of addressing modifiable lifestyle risk factors (MLRF) in that patient population remains largely unquantified. Methods This study quantified the potential effects of successfully managing 4 MLRF (smoking, obesity, alcohol consumption, and low physical activity) on the 10-year incidence of a first CVD diagnosis in adults with genetically confirmed FH treated with LLM within the UK Biobank. The synthesised causal estimates of these 4 MLF were obtained using two recent causal analysis frameworks, namely the doWhy causal calculus framework and the Causal Forest Double Machine Learning Method. Results In 660 FH individuals (mean age 56±8 years; 60.15% women), smoking cessation and reducing body mass index below 30 kg/m2 delivered the most substantial risk reductions (pooled estimates, adjusted for the 3 other MLRF: -6.5% and -3.2%, respectively; both p&amp;lt;0.001), followed by initiating moderate or high physical activity (-1.7%; p&amp;lt;0.001; Figure). Notably, cessation of alcohol consumption significantly increased CVD risk (+2.5%; p&amp;lt;0.001), aligning with existing literature. Conclusion In over 10 years, reductions in CVD risk ranging from 1.7% to 6.5% were achievable through smoking cessation, BMI reduction, and enhanced physical activity in FH individuals. Leveraging causal inference methodologies facilitates the discernment of which risk factors offer the most pronounced additional benefits beyond lipid-lowering interventions in this high-risk population.Forest Plot of Causal Effect Estimates

Effects of glyphosate based herbicide exposure in early developmental stages of Physalaemus gracilis

The impact of environmental pollutants has been a focus of investigation in recent years. Studies assessing the effects of these pollutants are essential for understanding the challenges faced by non-target species. Among the many substances used for agricultural purposes, the herbicide glyphosate is one of the most widely marketed in recent years. This broad-spectrum herbicide is commonly used to protect a variety of crops. In this study, we evaluated the effects of chronic glyphosate exposure on a native amphibian species, Physalaemus gracilis. Amphibians, which develop in aquatic environments, are highly sensitive to pesticides. Because of this, we investigated morphological, physiological, behavioral, and biochemical parameters in the early stages of development. The animals were exposed to environmentally relevant concentrations of a glyphosate-based herbicide (0, 100, 350, and 700 µg L⁻¹) during their first seven days of life. As a result, we observed impairments in anti-predatory behavior, reduced body mass index, and scaled mass index, malformations of the mouth and intestine, increased acetylcholinesterase activity, cardiotoxicity, and oxidative stress. These findings underscore the importance of studying native non-target species and highlight the need to evaluate the effects of environmentally relevant concentrations, as well as to review legislation regarding permissible levels of glyphosate in surface water and public water supplies.

Characterizing body composition modifying effects of a glucagon-like peptide 1 receptor-based agonist: A meta-analysis.

Diabetes is an independent risk factor for muscle mass loss, with possible mechanisms including impaired insulin signalling and chronic inflammation. The use of a glucagon-like peptide 1 (GLP-1) receptor-based agonist could lead to weight reduction, which might result from the loss of both fat and skeletal muscle. However, the body composition-modifying effects of GLP-1 receptor-based agonists have not been systematically characterized. PubMed, EMBASE, the Cochrane Center Register of Controlled Trials for Studies and Clinicaltrial.gov were searched from inception to October 2023. Randomized controlled trials of GLP-1 receptor agonist or glucose-dependent insulinotropic polypeptide/GLP-1 receptor dual agonist, which reported the changes of body composition, were included. The results were computed as weighted mean differences (WMDs) and 95% confidence intervals (CIs) in a random-effects model. In all, 19 randomized controlled trials were included. When compared with controls, substantial reductions in fat body mass were observed in patients using GLP-1 receptor-based agonist treatment (WMD = -2.25 kg, 95% CI -3.40 to -1.10 kg), with decrease in areas of both subcutaneous fat (WMD = -38.35 cm2, 95% CI, -54.75 to -21.95 cm2) and visceral fat (WMD = -14.61 cm2, 95% CI, -23.77 to -5.44 cm2). Moreover, greater reductions in lean body mass were also observed in GLP-1 receptor-based agonist users compared with non-users (WMD = -1.02 kg, 95% CI, -1.46 to -0.57 kg), while the changes in lean mass percentage were comparable between GLP-1 receptor-based agonist users and non-users. Compared with the controls, GLP-1 receptor-based agonist users experienced greater reductions in fat body mass, with body shaping effects in terms of both subcutaneous fat mass and visceral fat mass. Although greater reductions in lean body mass were also observed in GLP-1 receptor-based agonist users, the changes in lean mass percentage were comparable between the users and non-users.

8780 The Role of Nuclear Receptor Corepressors 1 and 2 on Intestinal Carbohydrate Transport in Mice

Abstract Disclosure: M.J. Ritter: None. I. Amano: None. A.H. van der Spek: None. H.E. Daniel: None. A.N. Hollenberg: None. The nuclear receptor corepressors NCoR1 and NCoR2 are two critical regulators of metabolism that are required for maintaining metabolic homeostasis. Both NCoR1 and NCoR2 (also known as the silencing mediator of retinoic acid and thyroid hormone receptors; SMRT) recruit histone deacetylase 3 (HDAC3) to their deacetylase domain (DAD) to repress nuclear receptor (NR) target gene expression. Interruption of the DAD of NCoR1 in mice leads to lower body weight, decreased whole-body fat mass, insulin sensitization with altered oscillatory patterns of key metabolic genes (1). On the other hand, total body knock-out (KO) of SMRT leads to weight gain, insulin resistance, and hepatic steatosis with an increase in hepatic lipogenesis (2). Previously, we showed that the KO of NCoR1 and SMRT in tandem from adult mice led rapidly to weight loss, hypoglycemia, hypothermia and was lethal. Reductions in intestinal carbohydrate transporters were seen, including sodium-glucose linked transporter-1 (SGLT1), glucose transporter 2 (GLUT2), and glucose transporter 5 (GLUT5) (3). Thus, we hypothesized that NCoR1 and SMRT play unique roles in regulating intestinal carbohydrate metabolism, in turn controlling metabolic parameters including body mass and glucose levels. We then generated a novel model to enable KO of NCoR1 and SMRT throughout intestinal epithelial cells (IECs) in adult mice using a tamoxifen inducible cre under control of the villin 1 promoter. Mice were injected with tamoxifen and body weight and glucose were monitored daily. This was followed by both oral and intraperitoneal glucose tolerance testing (GTT) and metabolic phenotyping. Preliminary data showed that NCoR1 and SMRT KO leads to sustained weight loss and hypoglycemia with 50% survivability. Metabolic phenotyping confirmed reduction in body mass without concomitant reduction in food intake. Oral GTT showed a blunted peak in response to glucose gavage compared to intraperitoneal administration. Gene expression analysis showed reduction in SGLT1, GLUT2, and GLUT5 in addition to changes in metabolic pathways associated with fatty acid metabolism. Here, we show that NCoR1 and SMRT are critical regulators of body mass and glucose in part via their actions on carbohydrate transporters in the intestine. With the global burden of metabolic diseases, including obesity and diabetes, ever-rising, NCoR1 and SMRT represent an overlooked but important area of study to better our understanding of disease processes and identify new targets for treatment. We next aim to determine the functional mechanism by which weight loss and hypoglycemia develop in addition to identifying molecular targets and pathways regulated by NCoR1 and SMRT in IECs.

8699 ​​Efficacy of Glucagon-like Peptide-1 Analogs In Women With Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Abstract Disclosure: F.A. Kelly: None. A.D. Lôbo: None. I.P. da Silva: None. J.C. Cardoso: None. M.S. Barros: None. F.D. Pessôa: None. M.G. Leite: None. R.Y. Ura Sudo: None. A.M. De Almeida: None. F.A. Moraes: None. V. Morbach: None. M.C. Souza: None. P.G. Lima: None. M.P. Lima: None. I.B. Andrade: None. M.B. Jardine: None. L.M. Lopes: None. Polycystic ovary syndrome (PCOS) affects one in ten women of reproductive age, painting a complex picture of metabolic dysfunction. Its hallmark triad includes irregular menstrual cycles, androgen excess, and polycystic ovaries. Beyond infertility concerns, PCOS carries a heavy burden of metabolic imbalances, often characterized by insulin resistance, dyslipidemia, and chronic low-grade inflammation. These intertwined factors place women with PCOS at increased risk for type 2 diabetes and cardiovascular disease, posing a significant long-term health challenge. Current first-line treatments like metformin focus mainly on managing insulin resistance and regulating menstrual cycles. However, unmet needs remain in addressing the broader metabolic derangements and preventing associated health complications. In light of this, glucagon-like peptide-1 (GLP-1) analogs have emerged as potential game-changers in the PCOS treatment landscape. Their multifaceted effects on metabolism beyond blood sugar regulation offer a promising avenue for optimizing care and improving long-term health outcomes in women with PCOS. This meta-analysis aims to evaluate the use of GLP-1 analogs on patients with PCOS to reduce body mass index (BMI), glycated hemoglobin (HbA1C), fasting blood glucose (FBG), high density lipid (HDL), low density lipid (LDL) and triglyceride. PubMed, Embase, and Cochrane databases were systematically searched for randomized controlled trials (RCT) comparing the use of GLP-1 analogs to placebo or other therapies in patients with PCOS. Treatment effects for continuous endpoints were pooled through mean differences (MD) with 95% confidence intervals. Heterogeneity was evaluated with the Cochran Q test, the prediction interval and I² statistics. Statistical analysis was performed in Revman 5.4. The results were reported following the Preferred Reporting Items for Systematic Review (PRISMA) guidelines.A total of 4 RCTs with 228 patients were included, of whom 137 were randomized to GLP-1 therapy, 58 to placebo, and 33 to other treatments. Over a mean follow-up time of 24 weeks, patients submitted to GLP-1 analogs presented significant decreases in HbA1C (MD -1.40%; 95% CI -1.64 to -1.16; p&amp;lt;000001; I²=0% ), FBG (MD -4.40 mg/dL; 95% CI -7.63 to -1.17; p=0.008; I²=0%) and HDL-c (MD -0.82 mg/dL; 95% CI -1.33 to -0.31; p=0.002; I²=3%); and a nonsignificant increase in LDL-c (MD 0.37 mg/dL; 95% CI -1.30 to 2.03; p=0.67; I²=0%); and nonsignificant decrease in BMI (MD -1.28 Kg/m²; 95% CI -3.18 to 0.63; p=0.19; I²=98%), and triglyceride (MD -10.50 mg/dL; 95% CI -22.81 to 1.81; p=0.09; I²=0%).In this meta-analysis of RCTs of patients with PCOS, the use of GLP-1 analogs showed a significant reduction in HbA1C, FBG, and HDL-c. A larger sample size of people are needed for further statistical analyses. Presentation: 6/3/2024

8687 The Efficacy of GLP1 Receptor Agonists in Obese Women with PCOS in Promoting Weight Loss and Hormonal Regulation: A Systematic Review and Meta-Analysis

Abstract Disclosure: B. Austregesilo Athayde H Morais: None. V.M. Prizão: None. B. Ximenes Mendes: None. M.L. Defante: None. O.C. Martins: None. T.L. Correa: None. M.D. De Moura de Souza: None. Background: GLP1 receptor antagonists (GLP1a) are known for their efficacy in promoting weight loss among obese and diabetic patients. However, their impact on weight reduction and hormonal regulation in obese females with polycystic ovarian syndrome (PCOS) remains understudied. Therefore, we aimed to perform a meta-analysis exploring the efficacy of GLP1a against placebo for ameliorating symptoms of PCOS. Hypothesis: The use of GLP1 receptor agonists in obese women with PCOS reduces body mass index and waist circumference as well as normalizes hormone levels such as total testosterone, total cholesterol, and HOMA-IR. Methods: We conducted a comprehensive search of PubMed, Cochrane, and Scopus databases to identify trials comparing GLP1a against placebo among women diagnosed with PCOS based on the Rotterdam Criteria. Our primary outcomes of interest included body mass index (BMI), triglycerides, waist circumference, total testosterone, total cholesterol, and HOMA-IR. We performed data extraction and quality assessment for studies that met the inclusion criteria. Subsequently, we conducted a statistical analysis using Review Manager 5.1.7 (Cochrane Collaboration). We evaluated heterogeneity using I² statistics. Results: We included 176 participants from 4 studies, which all were RCTs. GLP1a was used to treat 111 (63.06%) patients. Analyzed outcomes included waist circumference (MD: −5.16 cm; 95% CI: −6.11 to −4.21; p &amp;lt; 0.00001), total testosterone (MD: −1.33; 95% CI: −2.55 to −0.12; p =0.03), BMI (MD: -2.42; 95% CI: -3.10 to -1.74; p &amp;lt; 0.00001), total cholesterol (MD: −0.04; 95% CI: −0.10 to 0.01; p =0.15), HOMA-IR (MD: −0.30; 95% CI: −0.92 to 0.32; p =0.35), Triglycerides (MD: −0.20; 95% CI: −0.30 to −0.11; p &amp;lt; 0.00001) were lower in patients treated with GLP1a compared with placebo. Most patients who discontinued the trials did so because of a nausea side effect. Conclusion: The utilization of GLP1a demonstrates efficacy in reducing body mass index (BMI), triglycerides, waist circumference, total testosterone, total cholesterol, and HOMA-IR. These results signify its viability as a favorable treatment option for managing PCOS in obese females. Presentation: 6/3/2024

8040 Precision-Engineered Activin and GDF Ligand Trap HS235: A Novel Lean Mass-Preserving Treatment for Obesity

Abstract Disclosure: G. Schang: Employee; Self; 35Pharma. M. De Molliens: Employee; Self; 35Pharma. E. Brule: Employee; Self; 35Pharma. C. Chauvet: Employee; Self; 35Pharma. J. Denis: Employee; Self; 35Pharma. A. Sours: Employee; Self; 35Pharma. V. Ganesh: Employee; Self; 35Pharma. G. Tremblay: Employee; Self; 35Pharma. J. Schoelermann: Employee; Self; 35Pharma. M. O'Connor: Employee; Self; 35Pharma. 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, incretins reduce body mass in a non-selective manner; both fat mass and lean mass are lost with incretin treatment. In obese patients treated with incretins, undesirable loss of lean body mass (LBM) can account for up to 40% of overall weight loss. Loss of LBM negatively impacts resting metabolic rate, leading to a weight loss plateau and often unsustainable results. Furthermore, individuals with sarcopenia, characterized by low muscle mass and strength, are at greater risk for heart failure. The preservation, or even increase, of LBM is therefore a desirable treatment goal for obesity pharmacotherapy and overall cardiometabolic 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. 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. To 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, muscle weights, 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 lead to a synergistic fat mass loss and prevented loss of LBM. Conclusion: Potent and selective inhibition of activins and GDFs by HS235 represents a novel LBM preserving weight loss strategy orthogonal to incretin mimetics. Collectively, these data support the development of HS235 as a novel anti-obesity agent to complement currently approved incretin-based medications to improve quality of weight loss. Presentation: 6/3/2024

Depression and Obesity—Do We Know Everything about It? A Narrative Review

Introduction: Due to similarities in their pathophysiology and common psychological background, depressive disorders and obesity often occur simultaneously. The treatment of obesity can reduce the symptoms of comorbid depression and, conversely, treating depression can improve weight reduction outcomes. Purpose of this study: This review aimed to analyze the available literature on the subject of various methods of treating obesity and comorbid depression and to demonstrate the mutual correlation between the therapy of depressive disorders and the therapy of obesity. Method: The Pubmed and Cochrane databases were searched for original articles on the subject of simultaneous depression and obesity that had been published between 2014 and 2024, using the key words “depression”, “depressive symptoms”, “obesity”, and “behavioral therapy”. Results and conclusions: The successful treatment of depression can help in treating obesity, especially in motivating patients to adjust their lifestyle by changing dietary habits and increasing their physical activity, which contribute to both changes in body mass index scores and reductions in depressive symptoms. Changes in self-perception, reduced daily stress, and dietary changes, as well as increased physical activity, contribute to both weight loss and the reduction of depressive symptoms. Depression and obesity should be treated as one two-dimensional disorder to achieve better long-term treatment results.

Heightened mitochondrial respiration in CF cells is normalised by triple CFTR modulator therapy through mechanisms involving calcium

BackgroundCystic fibrosis (CF) is associated with increased resting energy expenditure. However, the introduction of elexacaftor/tezacaftor/ivacaftor (ETI) has resulted in a paradigm shift in nutritional status for many people with CF, with increase body mass index and reduction in the need for nutritional support. While these changes are likely to reflect improved clinical status and an associated downregulation of energy expenditure, they may also reflect drug-induced alterations in metabolic perturbations within CF cells. We hypothesise that some of these changes relate to normalisation of mitochondrial respiration in CF. MethodsUsing wild-type (WT) and F508del/F508del CFTR human bronchial epithelial cell lines (HBE cell lines) and baby hamster kidney (BHK) cells we examined the impact of ETI on cellular metabolism. We monitored mitochondrial respiration, using Seahorse extracellular flux assays and monitored mitochondrial reactive oxygen species (mROS) and intracellular calcium levels by flow cytometry. ResultsIncreased mitochondrial respiration was found in HBE cell lines and BHK cells expressing CFTR F508del/F508del when assessing basal, maximal, spare respiratory capacities and ATP production, as well as increased mitochondrial ROS generated via forward electron transport. ETI significantly decreased basal, maximal, spare respiratory capacity and ATP production to WT levels or below. Calcium blocker, BAPTA-AM normalised mitochondrial respiration, suggesting a calcium-mediated mechanism. ETI decreased intracellular calcium levels in CF cells to the same extent as BAPTA-AM, highlighting the importance of calcium and chloride in mitochondrial respiration in CF. ConclusionsCF cell lines exhibit increased mitochondrial respiration, which can be downregulated by ETI therapy through mechanisms involving calcium.

The effect of diets with different inflammatory scores on inflammation and sleep in obese subjects: a randomized controlled trial.

The aim of this study was to investigate the effect of different dietary inflammatory index diets on inflammatory markers, anthropometric measurements, and sleep quality in obese subjects. This study was conducted in a public hospital in Turkey between November 2021 and May 2022. Participants with pro-inflammatory dietary habits were included in the study. Randomly divided into two groups of 33 participants, they were subjected to an anti-inflammatory diet or a control diet for 8 weeks. The study evaluated the anthropometric parameters, inflammatory biomarkers, and sleep quality indices of the diet groups. Significant reductions in body mass index were observed in both groups, more marked in the anti-inflammatory diet cohort. C-reactive protein levels, indicative of inflammation, also decreased substantially in both groups, with a more marked reduction in the anti-inflammatory diet cohort. Despite the improvement in sleep quality in both groups, the variation was not statistically significant. This study demonstrates the importance of anti-inflammatory diets in nutritional strategies for obesity by reducing body mass index and inflammation.

The effects of exercise, heat-induced hypo-hydration and rehydration on blood-brain-barrier permeability, corticospinal and peripheral excitability.

The effects of low-intensity exercise, heat-induced hypo-hydration and rehydration on maximal strength and the underlying neurophysiological mechanisms are not well understood. To assess this, 12 participants took part in a randomised crossover study, in a prolonged (3h) submaximal (60W) cycling protocol under 3 conditions: (i) in 45°C (achieving ~ 5% body mass reduction), with post-exercise rehydration in 2h (RHY2), (ii) with rehydration across 24h (RHY24), and (iii) a euhydrated trial in 25°C (CON). Dependent variables included maximal voluntary contractions (MVC), maximum motor unit potential (MMAX), motor evoked potential (MEPRAW) amplitude and cortical silent period (cSP) duration. Blood-brain-barrier integrity was also assessed by serum Ubiquitin Carboxyl-terminal Hydrolase (UCH-L1) concentrations. All measures were obtained immediately pre, post, post 2h and 24h. During both dehydration trials, MVC (RHY2: p < 0.001, RHY24: p = 0.001) and MEPRAW (RHY2: p = 0.025, RHY24: p = 0.045) decreased from pre- to post-exercise. MEPRAW returned to baseline during RHY2 and CON, but not RHY24 (p = 0.020). MEP/MMAX ratio decreased across time for all trials (p = 0.009) and returned to baseline, except RHY24 (p < 0.026). Increased cSP (p = 0.011) was observed during CON post-exercise, but not during RHY2 and RHY24. Serum UCH-L1 increased across time for all conditions (p < 0.001) but was not significantly different between conditions. Our findings demonstrate an increase in corticospinal inhibition after exercise with fluid ingestion, but a decrease in corticospinal excitability after heat-induced hypo-hydration. In addition, low-intensity exercise increases peripheral markers of blood-brain-barrier permeability.Kindly check and confirm inserted city name correctly identified in affiliation 7This is correct.

Evaluation of the protective dose-dependent effect of metformin for induced osteoarthritis in rats.

To evaluate the potential protective effect of metformin against osteoarthritis development in rats. The experimental study was conducted at the Iraqi Centre for Cancer Research and Medical Genetics, Mustansiriyah University, Baghdad, Iraq, from December 2021 to February 2022, and comprised male Sprague- Dawley mice who were divided into 5 equal groups: negative control group, osteoarthritis group subjected to monoiodoacetate induction, positive control group treated with celecoxib 30mg/kg, metformin 100mg/kg group, and metformin 200mg/kg group. Body mass index, inflammatory biomarkers, and serum C-terminal cross-linked telopeptide of type II collagen levels were noted for all the animals. Data was analysed using SPSS 24. Of the 35 mice, 7(20%) were in each of the 5 groups. Compared to the osteoarthritis group, metformintreated mice showed significantly reduced body mass index, inflammatory biomarker levels, and blood levels of Cterminal cross-linked telopeptide of type II collagen (p=0.05). Metformin 200mg/kg treatment had more beneficial effects than 100mg/kg dose on inflammatory biomarkers and serum C-terminal cross-linked telopeptide of type II collagen (p=0.05). A beneficial protective effect against the onset of osteoarthritis was produced by metformin in a dosedependent way. Additionally, metformin could lessen cartilage damage as demonstrated by a decrease in the serum levels of C-terminal cross-linked telopeptide of type II collagen in the osteoarthritis group.