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OBE-DB: A Computational Tool and Web Server for the Prediction of Obesity Drugs. OBE-DB:用于预测减肥药的计算工具和Web服务器。
Pub Date : 2026-01-22 DOI: 10.1002/oby.70117
Elena Murcia-García, Carlos Martínez-Cortés, Antonio J Banegas-Luna, Juan José Hernández-Morante, Horacio Pérez-Sánchez

Objective: The huge obesity prevalence and related metabolic disorders highlight the urgent need for new therapeutic strategies beyond lifestyle interventions. Despite the availability of novel pharmacological treatments, the search for more effective and safe antiobesity compounds remains a challenge. Recent advances in high-performance computational drug discovery have enabled the rapid screening and identification of potential antiobesity compounds [Correction added on 10 February 2026, after first online publication: "Methods" was deleted from this sentence.]. However, these in silico procedures frequently require complex computational knowledge that limits the use of these techniques for most researchers and hampers interdisciplinary works.

Methods: To address this gap, we have developed OBE-DB, an accessible and user-friendly platform integrating computational tools that facilitates the prediction of potential antiobesity molecules through two complementary approaches: (i) shape similarity analysis against a curated database of approved obesity drugs and (ii) inverse virtual screening of user-submitted molecules against a set of therapeutic protein targets linked to obesity.

Results: Our results demonstrate that the server effectively screens and ranks compounds with high predicted activity, outperforming conventional in silico techniques in terms of accuracy and usability.

Conclusion: The OBE-DB web server represents a significant advancement by providing researchers with an intuitive tool to accelerate early-stage drug discovery for obesity treatment. The server is freely accessible without registration, providing users with a detailed report via email upon completion of the predictions. This innovative database and web server is accessible online via https://bio-hpc.ucam.edu/obe-db/.

目的:巨大的肥胖患病率和相关的代谢紊乱突出了迫切需要新的治疗策略,而不是生活方式干预。尽管有新的药物治疗方法,寻找更有效和安全的抗肥胖化合物仍然是一个挑战。方法:高性能计算药物发现的最新进展使快速筛选和鉴定潜在的抗肥胖化合物成为可能。然而,这些计算机程序通常需要复杂的计算知识,这限制了大多数研究人员对这些技术的使用,并阻碍了跨学科的工作。方法:为了解决这一差距,我们开发了OBE-DB,这是一个可访问且用户友好的平台,集成了计算工具,通过两种互补方法促进潜在抗肥胖分子的预测:(i)针对已批准的肥胖药物的策划数据库进行形状相似性分析;(ii)针对与肥胖相关的一组治疗性蛋白质靶点对用户提交的分子进行反向虚拟筛选。结果:我们的研究结果表明,该服务器有效地筛选和排列具有高预测活性的化合物,在准确性和可用性方面优于传统的硅技术。结论:OBE-DB web服务器为研究人员提供了一个直观的工具来加速早期肥胖治疗药物的发现,这是一个重大的进步。该服务器无需注册即可免费访问,在完成预测后通过电子邮件向用户提供详细的报告。这个创新的数据库和web服务器可以通过https://bio-hpc.ucam.edu/obe-db/在线访问。
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引用次数: 0
Exploring Sleep, Energy Balance, and Weight Loss Maintenance After Bariatric Surgery in Adult Females: A Cross-Sectional Study. 成年女性减肥手术后睡眠、能量平衡和体重维持:一项横断面研究。
Pub Date : 2026-01-21 DOI: 10.1002/oby.70124
Hannah R Koch, Derek C Monroe, Steve Fordahl, Graham Finlayson, Laurie Wideman, Jessica McNeil

Objective: This cross-sectional study examined associations between sleep, body weight, body composition, appetite, and food reward after bariatric surgery.

Methods: A single 7-day study period in 22 female adults (age, 53.5 ± 9.3 years; BMI, 35.5 ± 8.5 kg/m2; body fat: 44.9% ± 8.6%) who underwent bariatric surgery ≥ 1 year prior to enrollment assessed: actigraphy-measured sleep (duration, efficiency, midpoint, and variability [coefficient of variation]) and activity energy expenditure (AEE); sleep architecture and apnea-hypopnea index (AHI) via in-home polysomnography; energy intake via food diaries; resting EE via indirect calorimetry; fasting appetite via visual analog scales; and food reward via Leeds Food Preference Questionnaire.

Results: Weight regain was 10.6% relative to nadir postsurgery weight. Rapid eye movement (REM) sleep duration was associated with lower body fat percentage (r = -0.52, p = 0.02). Participants with AHI ≥ 5 had a greater waist to hip ratio compared to those with AHI < 5 (mean difference = 0.09, p = 0.01). Sleep timing and duration variability was associated with fasting prospective food consumption (r = 0.44, p = 0.05 and r = 0.47, p = 0.03, respectively). Greater sleep duration was associated with lower AEE (r = -0.62, p < 0.01) and explicit liking for sweet foods (r = 0.45, p = 0.04).

Conclusions: Our exploratory results underscore the need to evaluate whether sleep behaviors, including total and REM sleep duration, AHI, and sleep regularity, predict long-term weight loss maintenance after bariatric surgery.

目的:本横断面研究探讨了减肥手术后睡眠、体重、身体组成、食欲和食物奖励之间的关系。方法:对22名接受减肥手术≥1年的女性成人(年龄53.5±9.3岁,BMI 35.5±8.5 kg/m2,体脂:44.9%±8.6%)进行为期7天的研究,评估活动记录仪测量的睡眠(持续时间、效率、中点和变异性[变异系数])和活动能消耗(AEE);通过家庭多导睡眠仪检测睡眠结构和呼吸暂停低通气指数(AHI);通过食物日记摄入能量;间接量热法测静息EE;通过视觉模拟量表测定空腹食欲;和食物奖励通过利兹食物偏好问卷。结果:相对于术后最低体重,体重恢复率为10.6%。快速眼动(REM)睡眠持续时间与较低体脂率相关(r = -0.52, p = 0.02)。结论:我们的探索性结果强调了评估睡眠行为(包括总睡眠时间和快速眼动睡眠时间)、AHI和睡眠规律是否能预测减肥手术后长期体重维持的必要性。
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引用次数: 0
Addition of Phentermine-Topiramate to a Digitally Enhanced Lifestyle Intervention: A Double-Blind Randomized Clinical Trial. 芬特明-托吡酯加入数字增强生活方式干预:一项双盲随机临床试验。
Pub Date : 2026-01-21 DOI: 10.1002/oby.70108
Alejandro Campos, Wissam Ghusn, Lizeth Cifuentes, Daniel Sacoto, Sima Fansa, Diego Anazco, Maria L Ricardo-Silgado, Anas Hashem, Megan Schaefer, William S Harmsen, Heather J Gunn, Craig Peterson, Deborah Larsen, Santosh T Varghese, Maria D Hurtado, Andres Acosta

Objective: This study compared the effects of phentermine-topiramate-ER (mid-dose 7.5/46 mg) versus placebo on weight loss and cardiovascular disease (CVD) risk outcomes when used as an adjunct to a digitally enhanced lifestyle intervention (DELI).

Methods: We conducted a 12-month, randomized, double-blind, placebo-controlled trial at a single tertiary academic center in the United States (June 2020-June 2022). Eighty participants with obesity (BMI ≥ 30 kg/m2) were enrolled in the DELI program, consisting of in-person and telehealth modalities, dietary and physical activity goals, and use of a smartphone application integrated with digital devices (Apple Watch and Bluetooth-enabled weight scale and blood pressure monitor). Participants were randomized 1:1 to receive either phentermine-topiramate-ER (n = 42) or placebo (n = 38) in addition to the DELI.

Results: At 3 months, the phentermine-topiramate group lost a mean of 10.82 kg versus 4.04 kg in the placebo group (mean difference -6.78 kg; p = 0.002). At 12 months, weight loss was 15.32 kg versus 5.85 kg, respectively (mean difference -9.48 kg; p < 0.001). Participants receiving phentermine-topiramate-ER experienced a 3.35% reduction in the estimated atherosclerotic CVD risk compared to baseline (p = 0.004).

Conclusions: Phentermine-topiramate-ER, when combined with a DELI, produced significant and sustained weight loss and reduced CVD risk in adults with obesity.

Trial registration: ClinicalTrials.gov: NCT04408586.

目的:本研究比较芬特明-托吡酯- er(中剂量7.5/46 mg)与安慰剂作为数字增强生活方式干预(DELI)的辅助治疗对体重减轻和心血管疾病(CVD)风险结局的影响。方法:我们在美国一个高等教育中心进行了一项为期12个月的随机、双盲、安慰剂对照试验(2020年6月- 2022年6月)。80名肥胖参与者(BMI≥30 kg/m2)被纳入DELI项目,包括面对面和远程医疗模式,饮食和体育活动目标,以及与数字设备(苹果手表和蓝牙体重秤和血压监测仪)集成的智能手机应用程序的使用。除DELI外,参与者按1:1随机分配接受芬特明-托吡酯- er (n = 42)或安慰剂(n = 38)。结果:3个月时,芬特明-托吡酯组平均体重减轻10.82 kg,而安慰剂组平均体重减轻4.04 kg(平均差值-6.78 kg, p = 0.002)。12个月时,体重分别减轻15.32 kg和5.85 kg(平均差值-9.48 kg); p结论:芬特明-托吡酯- er与DELI联合使用,可显著持续减轻肥胖成人的体重,并降低心血管疾病风险。试验注册:ClinicalTrials.gov: NCT04408586。
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引用次数: 0
Epidemiology and Natural History of Preclinical and Clinical Obesity: Insights From a UK Cohort. 临床前和临床肥胖的流行病学和自然史:来自英国队列的见解。
Pub Date : 2026-01-20 DOI: 10.1002/oby.70126
Sohail Zahid, Zhiqi Yao, Seraj N Grimes, April Kim, Allison W Peng, Roger S Blumenthal, Marios Arvanitis, Alexis Battle, Michael J Blaha

Objective: Obesity has been traditionally defined by BMI alone, but this metric has limitations in assessing body fat composition and adiposity complications. The Lancet Diabetes and Endocrinology Commission (LDEC) issued a new obesity definition to address these challenges, stratified by preclinical and clinical groups. We evaluated the epidemiology of preclinical and clinical obesity in the UK Biobank and associations with incident cardiovascular disease (CVD).

Methods: We performed retrospective cohort analyses of 502,233 adults enrolled in the UK Biobank. Obesity was categorized using the new definition from LDEC. Clinical obesity was defined as adiposity-related dysfunction assessed via ICD10 codes, physical immobility, and abnormal laboratory values. Preclinical obesity had no additional metabolic deficits.

Results: The prevalence of preclinical and clinical obesity was 31.2% and 36.6%, and most were in the WHO overweight category. Clinical obesity was more prevalent in men, elderly, South Asians, and lower education or income level groups. Individuals with clinical obesity without baseline CVD had an increased hazard of incident stroke, heart failure, and myocardial infarction.

Conclusions: In a large UK cohort, preclinical and clinical obesity were common, but the risk for incident CVD was elevated for those with clinical obesity.

目的:肥胖传统上仅由BMI定义,但该指标在评估体脂组成和肥胖并发症方面存在局限性。柳叶刀糖尿病和内分泌委员会(LDEC)发布了一个新的肥胖定义来应对这些挑战,并根据临床前和临床组进行了分层。我们评估了英国生物银行中临床前和临床肥胖的流行病学以及与心血管疾病(CVD)的关联。方法:我们对在英国生物银行登记的502,233名成年人进行了回顾性队列分析。根据LDEC的新定义对肥胖进行了分类。临床肥胖被定义为通过ICD10编码、身体不活动和异常实验室值评估的肥胖相关功能障碍。临床前肥胖没有额外的代谢缺陷。结果:临床前和临床肥胖患病率分别为31.2%和36.6%,多数属于WHO超重类别。临床肥胖在男性、老年人、南亚人和低教育水平或收入人群中更为普遍。无基线CVD的临床肥胖个体发生卒中、心力衰竭和心肌梗死的风险增加。结论:在英国的一项大型队列研究中,临床前和临床肥胖很常见,但临床肥胖患者发生心血管疾病的风险升高。
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引用次数: 0
Psychiatric Safety of Tirzepatide in People With Obesity and No Known Major Psychopathology: A Post Hoc Analysis of SURMOUNT. 替西帕肽对肥胖且无主要精神病理的患者的精神安全性:一项对SURMOUNT的事后分析。
Pub Date : 2026-01-15 DOI: 10.1002/oby.70122
Thomas A Wadden, Maria A Oquendo, Robert F Kushner, Dachuang Cao, Chrisanthi A Karanikas, Afton Kechter, Madhumita A Murphy

Objective: This post hoc analysis assessed psychiatric changes with tirzepatide in adults with obesity, without known major psychopathology, from SURMOUNT-1, SURMOUNT-2, and SURMOUNT-3.

Methods: In participants (N = 4056) treated with tirzepatide (5/10/15 mg or maximum tolerated dose 10/15 mg) versus placebo, depressive symptoms and suicidal ideation and behavior (SI/SB) were measured using the Patient Health Questionnaire-9 (PHQ-9) and Columbia-Suicide Severity Rating Scale (C-SSRS), respectively. Nervous system and psychiatric disorder adverse events (AEs) were collected.

Results: Mean (SD) baseline PHQ-9 scores were 2.7 (3.0) for tirzepatide and 2.6 (3.1) for placebo, indicating no/minimal symptoms of depression. At week 72, scores were 1.9 (2.7) and 2.4 (3.3), respectively (estimated treatment difference [SE]: -0.6 [0.1]); p < 0.001. Tirzepatide-treated participants were less likely to shift to a more severe PHQ-9 category (18.2% vs. 24.3%; p < 0.001). Using the C-SSRS, 0.6% of participants in each group reported SI, most of which was considered low risk. SB (nonfatal) occurred in 0.1% of tirzepatide-treated participants versus none with placebo. AEs were generally similar across groups.

Conclusions: In this post hoc analysis, tirzepatide versus placebo did not appear to be associated with an increased risk of depression in participants with overweight/obesity and without known major psychopathology. Rates of SI/SB observed with tirzepatide were similar to those of other incretin-based therapies. Further study of tirzepatide's safety in persons with significant psychiatric illness may be warranted.

Trial registration: ClinicalTrials.gov identifiers: NCT04184622, NCT04657003, and NCT04657016.

目的:本事后分析从SURMOUNT-1、SURMOUNT-2和SURMOUNT-3评估成人肥胖患者使用替西帕肽的精神变化,无已知主要精神病理。方法:采用患者健康问卷-9 (PHQ-9)和哥伦比亚自杀严重程度评定量表(C-SSRS)分别测量替西帕肽(5/10/15 mg或最大耐受剂量10/15 mg)和安慰剂治疗组(N = 4056)的抑郁症状和自杀意念与行为(SI/SB)。收集神经系统和精神障碍不良事件(ae)。结果:替西帕肽组的平均(SD)基线PHQ-9评分为2.7(3.0),安慰剂组为2.6(3.1),表明无或只有轻微抑郁症状。在第72周,评分分别为1.9(2.7)和2.4(3.3)(估计治疗差异[SE]: -0.6 [0.1]);结论:在这项事后分析中,替西帕肽与安慰剂似乎与超重/肥胖且没有已知主要精神病理的参与者的抑郁风险增加无关。替西帕肽观察到的SI/SB率与其他以肠促胰岛素为基础的治疗相似。有必要进一步研究替西帕肽对严重精神疾病患者的安全性。试验注册:ClinicalTrials.gov标识符:NCT04184622、NCT04657003和NCT04657016。
{"title":"Psychiatric Safety of Tirzepatide in People With Obesity and No Known Major Psychopathology: A Post Hoc Analysis of SURMOUNT.","authors":"Thomas A Wadden, Maria A Oquendo, Robert F Kushner, Dachuang Cao, Chrisanthi A Karanikas, Afton Kechter, Madhumita A Murphy","doi":"10.1002/oby.70122","DOIUrl":"https://doi.org/10.1002/oby.70122","url":null,"abstract":"<p><strong>Objective: </strong>This post hoc analysis assessed psychiatric changes with tirzepatide in adults with obesity, without known major psychopathology, from SURMOUNT-1, SURMOUNT-2, and SURMOUNT-3.</p><p><strong>Methods: </strong>In participants (N = 4056) treated with tirzepatide (5/10/15 mg or maximum tolerated dose 10/15 mg) versus placebo, depressive symptoms and suicidal ideation and behavior (SI/SB) were measured using the Patient Health Questionnaire-9 (PHQ-9) and Columbia-Suicide Severity Rating Scale (C-SSRS), respectively. Nervous system and psychiatric disorder adverse events (AEs) were collected.</p><p><strong>Results: </strong>Mean (SD) baseline PHQ-9 scores were 2.7 (3.0) for tirzepatide and 2.6 (3.1) for placebo, indicating no/minimal symptoms of depression. At week 72, scores were 1.9 (2.7) and 2.4 (3.3), respectively (estimated treatment difference [SE]: -0.6 [0.1]); p < 0.001. Tirzepatide-treated participants were less likely to shift to a more severe PHQ-9 category (18.2% vs. 24.3%; p < 0.001). Using the C-SSRS, 0.6% of participants in each group reported SI, most of which was considered low risk. SB (nonfatal) occurred in 0.1% of tirzepatide-treated participants versus none with placebo. AEs were generally similar across groups.</p><p><strong>Conclusions: </strong>In this post hoc analysis, tirzepatide versus placebo did not appear to be associated with an increased risk of depression in participants with overweight/obesity and without known major psychopathology. Rates of SI/SB observed with tirzepatide were similar to those of other incretin-based therapies. Further study of tirzepatide's safety in persons with significant psychiatric illness may be warranted.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifiers: NCT04184622, NCT04657003, and NCT04657016.</p>","PeriodicalId":94163,"journal":{"name":"Obesity (Silver Spring, Md.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145971532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The MetaboHealth Score Enhances Insulin Resistance Metabotyping for Targeted Fat Loss: The PERSON Study. 代谢健康评分提高胰岛素抵抗代谢分型的目标脂肪减少:PERSON研究。
Pub Date : 2026-01-14 DOI: 10.1002/oby.70116
Jordi Morwani-Mangnani, Fatih A Bogaards, Alexander Umanets, Gabby B Hul, Anouk Gijbels, Gijs H Goossens, Joris Deelen, Marian Beekman, Lydia Afman, Ellen E Blaak, P Eline Slagboom

Objective: We previously identified distinct muscle and liver insulin resistance (IR) metabotypes in middle-aged and older adults. The PERSON study showed that a low-fat, high-protein, high-fiber diet benefits the muscle IR group, while a high-monounsaturated fatty acid diet benefits the liver IR group. We also developed the MetaboHealth score, reflecting risks of mortality, frailty, and cognitive decline. This study aimed to examine whether MetaboHealth interacts with IR metabotypes to influence (i) cardiometabolic health and (ii) body composition outcomes in the PERSON study, informing precision nutrition strategies.

Methods: In total, 242 adults aged 40-75 with IR were randomized to follow an isocaloric low-fat, high-protein, high-fiber or high-monounsaturated fatty acid diet for 12 weeks. Of these, 184 with complete data were grouped into MetaboHealth tertiles (higher = poorer health). Outcomes included a 7-point oral glucose tolerance test and DXA-based body composition. Linear mixed models assessed four-way interactions.

Results: No interaction was observed for cardiometabolic outcomes. Significant interactions were found for android, gynoid, total fat percentage, and fat mass index. In the healthiest tertile, matched diets led to greater fat loss. In the poorest tertile, both diets were similarly effective. MetaboHealth remained unchanged.

Conclusions: Combining metabotype with MetaboHealth may enhance personalized dietary strategies for fat loss in insulin-resistant adults.

目的:我们之前在中老年人群中发现了不同的肌肉和肝脏胰岛素抵抗(IR)代谢类型。PERSON研究表明,低脂肪、高蛋白、高纤维饮食对肌肉IR组有益,而高单不饱和脂肪酸饮食对肝脏IR组有益。我们还开发了代谢健康评分,反映死亡、虚弱和认知能力下降的风险。本研究旨在检查代谢健康是否与IR代谢型相互作用,以影响PERSON研究中的(i)心脏代谢健康和(ii)身体成分结果,为精确营养策略提供信息。方法:共有242名年龄在40-75岁之间的IR患者被随机分组,接受等热量低脂、高蛋白、高纤维或高单不饱和脂肪酸饮食12周。其中,184个数据完整的人被分为代谢健康组(越高=健康越差)。结果包括7点口服葡萄糖耐量试验和基于dxa的身体成分。线性混合模型评估了四方相互作用。结果:没有观察到对心脏代谢结果的相互作用。android、gynoid、总脂肪百分比和脂肪质量指数之间存在显著的相互作用。在最健康的人群中,匹配的饮食减少了更多的脂肪。在最贫穷的人群中,两种饮食的效果相似。代谢健康保持不变。结论:结合代谢型和代谢健康可以提高胰岛素抵抗成人减脂的个性化饮食策略。
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引用次数: 0
Weekly Subcutaneous VK2735, a GIP/GLP-1 Receptor Dual Agonist, for Weight Management: Phase 2, Randomized, 13-Week VENTURE Study. 每周皮下注射一种GIP/GLP-1受体双激动剂VK2735,用于体重控制:2期,随机,13周的VENTURE研究
Pub Date : 2026-01-08 DOI: 10.1002/oby.70106
Harold E Bays, Phillip Toth, Naim Alkhouri, John Pullman, Bradley Freilich, Joel Neutel, Summer Ji, Scott Stubbe, Parke Hedges, Brian Lian

Objective: This study aimed to determine doses of VK2735, a novel glucagon-like peptide-1/glucose-dependent insulinotropic polypeptide (GLP-1/GIP) receptor dual agonist, that are effective for weight loss over 13 weeks of treatment.

Methods: VENTURE was a phase 2, randomized, double-blind, placebo-controlled, dose-ranging study of weekly subcutaneous VK2735 in adults with obesity or overweight and ≥ 1 weight-related comorbidity. Participants with diabetes mellitus were ineligible. The primary endpoint was percent change from baseline in body weight at Week 13. Secondary efficacy endpoints were observed and change from baseline weight loss and the proportion of participants losing ≥ 5% and ≥ 10% of baseline weight.

Results: Study was conducted between August 2023 and February 2024. Mean weight reduction with active treatment ranged from 9.2 kg (2.5 mg dose) to 14.6 kg (15 mg dose), corresponding to 9.1% and 14.7% weight reductions, respectively; the placebo group had a 1.8 kg (1.7%) reduction. In the active treatment groups, 93% (130/140) of participants had a ≥ 5% weight reduction, compared with 12% (4/34) of participants with placebo treatment. The common adverse events (AEs) were gastrointestinal, which decreased in reported frequency after dose titration to steady state.

Conclusions: All subcutaneous doses of VK2735 significantly reduced body weight. The AE profile of VK2735 was primarily gastrointestinal, with decreased reported frequency upon continued use.

Trial registration: ClinicalTrials.gov identifier NCT06068946.

目的:本研究旨在确定VK2735的剂量,VK2735是一种新型胰高血糖素样肽-1/葡萄糖依赖性胰岛素性多肽(GLP-1/GIP)受体双激动剂,治疗13周后可有效减轻体重。方法:VENTURE是一项2期、随机、双盲、安慰剂对照、剂量范围研究,在肥胖或超重且体重相关合并症≥1例的成年人中,每周皮下注射VK2735。患有糖尿病的参与者不符合条件。主要终点是第13周体重较基线变化的百分比。观察次要疗效终点和基线体重减轻的变化,以及基线体重减轻≥5%和≥10%的参与者比例。结果:研究于2023年8月至2024年2月进行。积极治疗的平均体重减轻范围从9.2公斤(2.5毫克剂量)到14.6公斤(15毫克剂量),分别对应9.1%和14.7%的体重减轻;安慰剂组体重减少1.8公斤(1.7%)。在积极治疗组中,93%(130/140)的参与者体重减轻≥5%,而安慰剂治疗组为12%(4/34)。常见的不良事件(ae)是胃肠道,在剂量滴定至稳定状态后报道的频率下降。结论:所有皮下剂量的VK2735均能显著降低体重。VK2735的AE主要发生在胃肠道,持续使用后报告频率下降。试验注册:ClinicalTrials.gov识别码NCT06068946。
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引用次数: 0
Genetic Risk Scores for Obesity and the Effectiveness of a Diet and Exercise Intervention Program: A Historical Cohort Study. 肥胖的遗传风险评分和饮食和运动干预计划的有效性:一项历史队列研究。
Pub Date : 2025-12-28 DOI: 10.1002/oby.70118
Sho Nakamura, Miho Yanai, Amane Eto, Shinya Eto, Yoshinobu Saito, Takayuki Suzuki, Takeshi Seto, Hiroto Narimatsu

Objective: The role of genetic risk scores (GRS) in predicting responses to the obesity interventions in Japanese individuals remains underexplored. We aimed to examine GRS and introduce and evaluate a novel efficiency score derived from data envelopment analysis (DEA) for predicting the outcomes of a combined diet and exercise program.

Methods: Data from 145 individuals who completed an 8- to 12-week low-carbohydrate diet and resistance training intervention were retrospectively analyzed. GRS were calculated from 75 SNPs identified in a previous Japanese genome-wide association study. DEA was applied to generate efficiency scores using GRS as an input reflecting genetic load and initial BMI and body fat percentage as outputs reflecting phenotypic status. Linear regression analyses were performed to compare the predictive utility of GRS and efficiency scores.

Results: BMI and other measures decreased following the intervention. Linear-regression analyses revealed that DEA-derived efficiency scores strongly predicted the change in BMI percentage, whereas GRS did not.

Conclusions: Weight loss was achieved independently of GRS. GRS-derived efficiency score offered superior prediction of intervention effectiveness to that of GRS alone, suggesting that while GRS based on cross-sectional data may not predict responsiveness to interventions, integrated metrics also incorporating phenotypic data show potential for personalizing weight management strategies, pending further validation.

目的:遗传风险评分(GRS)在预测日本个体对肥胖干预反应中的作用仍未得到充分探讨。我们的目的是检验GRS,并引入和评估一种新的效率评分,该评分来源于数据包络分析(DEA),用于预测饮食和运动组合计划的结果。方法:回顾性分析145名完成8- 12周低碳水化合物饮食和阻力训练干预的患者的数据。GRS是根据之前日本全基因组关联研究中发现的75个snp计算出来的。采用DEA生成效率评分,GRS作为反映遗传负荷的输入,初始BMI和体脂率作为反映表型状态的输出。采用线性回归分析比较GRS和效率评分的预测效用。结果:干预后BMI等指标下降。线性回归分析显示,dea衍生的效率评分强有力地预测了BMI百分比的变化,而GRS则没有。结论:体重减轻与GRS无关。GRS衍生的效率评分对干预效果的预测优于单独的GRS,这表明尽管基于横截面数据的GRS可能无法预测对干预的反应性,但结合表型数据的综合指标显示出个性化体重管理策略的潜力,有待进一步验证。
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引用次数: 0
Senescent Mesenchymal Stromal Cells Differentially Alter Adipogenesis in Adipose Tissue, Skeletal Muscle, and Bone Marrow. 衰老的间充质间质细胞不同程度地改变脂肪组织、骨骼肌和骨髓的脂肪形成。
Pub Date : 2025-12-24 DOI: 10.1002/oby.70119
Xu Zhang, Madison L Doolittle, Ting Fan, Utkarsh Tripathi, Yan Er Ng, Xinyi Jiang, João F Passos, Diana Jurk, David G Monroe, Tamara Tchkonia, James L Kirkland, Paul D Robbins, Sundeep Khosla, Nathan K LeBrasseur

Objective: Aging alters mesenchymal stromal cell (MSC) function, leading to dysregulated adipogenesis across tissues through biased lineage commitment. Fat redistribution from adipose depots to skeletal muscle and bone marrow is common in aging, but the underlying mechanisms remain unclear. This study investigates how MSC senescence modulates adipogenesis.

Methods: Primary MSCs were isolated from mouse skeletal muscle (FAPs), adipose tissue (APCs), and bone marrow (BMSCs). Single-cell RNA sequencing was performed to compare transcriptional profiles among these populations. In vitro adipogenic differentiation and DNA damage-induced senescence assays were conducted, and the effects of autologous conditioned media from senescent MSCs on adipogenesis were assessed.

Results: Transcriptional analyses revealed that FAPs and APCs share greater similarity with each other than with BMSCs. All MSC types exhibited adipogenic potential and developed a robust senescence-associated secretory phenotype (SASP) upon senescence induction. Conditioned media from senescent MSCs enhanced adipogenesis in BMSCs but inhibited adipogenesis in FAPs and APCs, revealing tissue-specific paracrine effects.

Conclusions: MSC senescence reprograms adipogenic bias in a tissue-dependent, non-cell autonomous manner, contributing to age-related fat redistribution among adipose tissue, skeletal muscle, and bone marrow. Understanding these mechanisms may provide new therapeutic approaches for improving tissue composition and function in the context of aging.

目的:衰老改变间充质间质细胞(MSC)功能,通过偏向谱系承诺导致组织脂肪生成失调。脂肪从脂肪库重新分布到骨骼肌和骨髓在衰老过程中很常见,但其潜在机制尚不清楚。本研究探讨MSC衰老如何调节脂肪形成。方法:从小鼠骨骼肌(FAPs)、脂肪组织(APCs)和骨髓(BMSCs)中分离原代MSCs。进行单细胞RNA测序以比较这些人群的转录谱。我们进行了体外成脂分化和DNA损伤诱导衰老实验,并评估了衰老MSCs的自体条件培养基对脂肪形成的影响。结果:转录分析显示,FAPs和APCs之间的相似性大于与BMSCs之间的相似性。所有类型的MSC都表现出脂肪生成潜能,并在衰老诱导后发展出强大的衰老相关分泌表型(SASP)。来自衰老间充质干细胞的条件培养基增强了间充质干细胞的脂肪生成,但抑制了FAPs和apc的脂肪生成,揭示了组织特异性的旁分泌效应。结论:间质干细胞衰老以一种组织依赖的、非细胞自主的方式重新编程了脂肪生成偏向,促进了脂肪组织、骨骼肌和骨髓中与年龄相关的脂肪重新分配。了解这些机制可能为改善衰老背景下的组织组成和功能提供新的治疗方法。
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引用次数: 0
Soda Sugar Supertaxes Pave the Way for a Large Increase in Consumption of Sweeteners and Its Long-Term Effects. 苏打糖附加税为甜味剂消费的大幅增加及其长期影响铺平了道路。
Pub Date : 2025-12-15 DOI: 10.1002/oby.70114
Teresa Gonzalez, Roland Govers

As governments become aware of the increasing prevalence of obesity in their countries, they install taxes for the amount of sugar in sodas. This is leading to reductions in sugar intake and cardiovascular disease, as predicted, but unintentionally also to considerable increases in the consumption of non-nutritive sweeteners (NNS). Since many studies on the safety of NNS are highly conflicting, it is unclear at present whether NNS are a healthy substitute for sugar.

随着各国政府意识到肥胖在本国日益普遍,他们开始对碳酸饮料中的含糖量征税。正如预测的那样,这导致了糖摄入量和心血管疾病的减少,但无意中也导致了非营养性甜味剂(NNS)消费量的大幅增加。由于许多关于NNS安全性的研究存在高度矛盾,目前还不清楚NNS是否是糖的健康替代品。
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引用次数: 0
期刊
Obesity (Silver Spring, Md.)
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