Taggert J. Barton, McRae A. Bird, Seth W. Rather, Sheldon E. Litwin, Ted D. Adams, Steven C. Hunt, Lance E. Davidson
Objective
This study addressed the paucity of data exploring long-term effects of metabolic and bariatric surgery (MBS)-related weight loss on fitness.
Methods
Data from MBS patients (SURG; n = 82) and comparable non-surgery participants (NSURG; n = 88) were collected from a subset of a prospective trial, the Utah Obesity Study. Fitness was assessed through maximal and submaximal treadmill tests using a modified Bruce protocol. Submaximal exercise tests were performed preceding surgery at baseline and 11.5 years later. A subset (n = 97) of the 170 participants also performed maximal treadmill tests 2 and 6 years after baseline. Weight and BMI were recorded at each visit. Between-group treadmill time comparisons were adjusted for sex and weight.
Results
As expected, SURG had lower BMI and weight than NSURG at all follow-up visits (p < 0.0001). Treadmill time, adjusted for sex, baseline treadmill time, and weight over the 11.5-year period, was elevated in surgery compared to non-surgery groups at all follow-up visits (p < 0.01), but the fitness advantage gradually decreased over time.
Conclusions
An initially dramatic fitness benefit achieved with weight loss in MBS patients gradually declined but remained higher than non-surgery counterparts beyond a decade. An emphasis on physical activity may help sustain improved fitness after bariatric surgery.
目的：本研究解决了代谢和减肥手术（MBS）相关减肥对健康的长期影响的数据缺乏问题。方法：来自MBS患者（SURG, n = 82）和类似的非手术参与者（NSURG, n = 88）的数据来自前瞻性试验犹他肥胖研究的一个子集。采用改进的Bruce方案，通过最大和次最大跑步机测试评估体能。手术前基线和11.5年后分别进行亚极限运动测试。170名参与者中的一个子集（n = 97）在基线后2年和6年也进行了最大跑步机测试。在每次访问时记录体重和BMI。组间跑步时间比较根据性别和体重进行了调整。结果：正如预期的那样，在所有随访中，SURG的BMI和体重都低于NSURG (p)。结论：MBS患者最初通过减肥获得的显著健康益处逐渐下降，但在10年后仍高于非手术患者。强调体育活动可能有助于在减肥手术后保持良好的健康。
{"title":"Long-Term Benefit of Gastric Bypass Surgery on Fitness","authors":"Taggert J. Barton, McRae A. Bird, Seth W. Rather, Sheldon E. Litwin, Ted D. Adams, Steven C. Hunt, Lance E. Davidson","doi":"10.1002/oby.70048","DOIUrl":"10.1002/oby.70048","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study addressed the paucity of data exploring long-term effects of metabolic and bariatric surgery (MBS)-related weight loss on fitness.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data from MBS patients (SURG; <i>n</i> = 82) and comparable non-surgery participants (NSURG; <i>n</i> = 88) were collected from a subset of a prospective trial, the Utah Obesity Study. Fitness was assessed through maximal and submaximal treadmill tests using a modified Bruce protocol. Submaximal exercise tests were performed preceding surgery at baseline and 11.5 years later. A subset (<i>n</i> = 97) of the 170 participants also performed maximal treadmill tests 2 and 6 years after baseline. Weight and BMI were recorded at each visit. Between-group treadmill time comparisons were adjusted for sex and weight.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>As expected, SURG had lower BMI and weight than NSURG at all follow-up visits (<i>p</i> < 0.0001). Treadmill time, adjusted for sex, baseline treadmill time, and weight over the 11.5-year period, was elevated in surgery compared to non-surgery groups at all follow-up visits (<i>p</i> < 0.01), but the fitness advantage gradually decreased over time.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>An initially dramatic fitness benefit achieved with weight loss in MBS patients gradually declined but remained higher than non-surgery counterparts beyond a decade. An emphasis on physical activity may help sustain improved fitness after bariatric surgery.</p>\u0000 \u0000 <div>\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":"33 12","pages":"2289-2295"},"PeriodicalIF":4.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kathleen R. Ruddiman, Jessica K. Bartfield, Irl B. Hirsch
The presence of excess weight is no longer a distinguishing feature between patients with type 1 diabetes (T1D) and those with type 2 diabetes (T2D). Obesity treatment in patients with T2D improves glycemic control and reduces or even eliminates medication burden. Robust evidence and clear guidelines exist to support and direct effective weight management in patients with T2DM. Now, however, rates of obesity in patients with T1D rival those found in the general population, yet little is known about the efficacy, safety, and unique considerations of obesity treatment (lifestyle modifications, pharmacology, and surgery) in this population. This review tackles these topics and the gaps in evidence and clinical care.
{"title":"Understanding the Increasing Prevalence of Obesity in Patients With Type 1 Diabetes: Strategies for Improving Clinical Care","authors":"Kathleen R. Ruddiman, Jessica K. Bartfield, Irl B. Hirsch","doi":"10.1002/oby.70033","DOIUrl":"10.1002/oby.70033","url":null,"abstract":"<p>The presence of excess weight is no longer a distinguishing feature between patients with type 1 diabetes (T1D) and those with type 2 diabetes (T2D). Obesity treatment in patients with T2D improves glycemic control and reduces or even eliminates medication burden. Robust evidence and clear guidelines exist to support and direct effective weight management in patients with T2DM. Now, however, rates of obesity in patients with T1D rival those found in the general population, yet little is known about the efficacy, safety, and unique considerations of obesity treatment (lifestyle modifications, pharmacology, and surgery) in this population. This review tackles these topics and the gaps in evidence and clinical care.</p>","PeriodicalId":215,"journal":{"name":"Obesity","volume":"33 12","pages":"2246-2263"},"PeriodicalIF":4.7,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/oby.70033","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145240743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Han Yu, Jessica G. Young, Joshua Petimar, Sheryl L. Rifas-Shiman, Matthew F. Daley, William J. Heerman, David M. Janicke, W. Schuyler Jones, Takuya Kawahara, Kristina H. Lewis, Pi-I D. Lin, Sengwee Toh, Daniel S. Weisholtz, Jason P. Block
Objective
To estimate long-term weight change after initiation and adherence to commonly used antiseizure medications (ASMs) and examine differences in weight change across ASMs compared to topiramate.
Methods
We included 52,309 adult patients who initiated ASMs, applied a target trial emulation approach to control time-varying confounding and selection bias, and examined the long-term comparative effects on weight change after initiating and adhering to different ASMs at 6 and 12 months post initiation.
Results
The most commonly initiated ASM was topiramate (41.2%). In comparison to topiramate, we estimated higher 6-month weight change under initiation and adherence to levetiracetam 0.94 kg (95% CI 0.20, 1.64), lamotrigine 1.44 kg (0.74, 1.99), valproate 2.42 kg (1.71, 2.88), carbamazepine 1.32 kg (0.46, 2.16), and oxcarbazepine 1.74 kg (0.85, 2.71), with similar results at 12 months and in sensitivity and subgroup analyses. These results were driven mostly by weight loss with use of topiramate rather than weight gain with use of other ASMs. Results were similar though attenuated when accounting for medication initiation only.
Conclusions
Topiramate was associated with weight loss at 6 and 12 months under either initiation and subsequent adherence or initiation-only effects; other medications were associated with higher weight change. These results provided important information to help with decision-making regarding ASM initiation.
目的：评估开始和坚持使用常用抗癫痫药物（asm）后的长期体重变化，并检查与托吡酯相比，asm之间体重变化的差异。方法：我们纳入了52,309例开始使用asm的成年患者，采用目标试验模拟方法来控制时变混淆和选择偏差，并研究了在开始使用和坚持不同asm后6个月和12个月的体重变化的长期比较效应。结果：最常见的ASM是托吡酯（41.2%）。与托吡酯相比，我们估计左乙拉西坦和坚持左乙拉西坦的6个月体重变化更高0.94 kg (95% CI 0.20, 1.64)，拉莫三嗪1.44 kg(0.74, 1.99)，丙戊酸2.42 kg(1.71, 2.88)，卡马西平1.32 kg(0.46, 2.16)，奥卡西平1.74 kg(0.85, 2.71)，在12个月的敏感性和亚组分析中结果相似。这些结果主要是由于使用托吡酯导致体重减轻，而不是使用其他asm导致体重增加。结果相似，但当只考虑药物开始时，结果有所减弱。结论：在起始和后续依从性或仅起始效应下，托吡酯在6个月和12个月时的体重减轻相关；其他药物则与较高的体重变化有关。这些结果为ASM启动决策提供了重要信息。
{"title":"Long-Term Medication-Induced Weight Change Across Common Antiseizure Medications: A Target Trial Emulation Study","authors":"Han Yu, Jessica G. Young, Joshua Petimar, Sheryl L. Rifas-Shiman, Matthew F. Daley, William J. Heerman, David M. Janicke, W. Schuyler Jones, Takuya Kawahara, Kristina H. Lewis, Pi-I D. Lin, Sengwee Toh, Daniel S. Weisholtz, Jason P. Block","doi":"10.1002/oby.24362","DOIUrl":"10.1002/oby.24362","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To estimate long-term weight change after initiation and adherence to commonly used antiseizure medications (ASMs) and examine differences in weight change across ASMs compared to topiramate.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We included 52,309 adult patients who initiated ASMs, applied a target trial emulation approach to control time-varying confounding and selection bias, and examined the long-term comparative effects on weight change after initiating and adhering to different ASMs at 6 and 12 months post initiation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The most commonly initiated ASM was topiramate (41.2%). In comparison to topiramate, we estimated higher 6-month weight change under initiation and adherence to levetiracetam 0.94 kg (95% CI 0.20, 1.64), lamotrigine 1.44 kg (0.74, 1.99), valproate 2.42 kg (1.71, 2.88), carbamazepine 1.32 kg (0.46, 2.16), and oxcarbazepine 1.74 kg (0.85, 2.71), with similar results at 12 months and in sensitivity and subgroup analyses. These results were driven mostly by weight loss with use of topiramate rather than weight gain with use of other ASMs. Results were similar though attenuated when accounting for medication initiation only.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Topiramate was associated with weight loss at 6 and 12 months under either initiation and subsequent adherence or initiation-only effects; other medications were associated with higher weight change. These results provided important information to help with decision-making regarding ASM initiation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":"33 12","pages":"2355-2364"},"PeriodicalIF":4.7,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145234870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Interpreting GLP-1RA Cost-Effectiveness: A Call for Caution","authors":"Qing Xia","doi":"10.1002/oby.70036","DOIUrl":"10.1002/oby.70036","url":null,"abstract":"","PeriodicalId":215,"journal":{"name":"Obesity","volume":"33 11","pages":"2023-2024"},"PeriodicalIF":4.7,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145234819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xingfang Wang, Jianhua Gu, Shuo Wu, Ping Fu, Jiqing Li
Objective
This study aimed to characterize the longitudinal trajectory of the body roundness index (BRI) in a multinational cohort and to investigate its association with cardiovascular disease (CVD) events.
Methods
We pooled individual-level data from three prospective cohort studies across the United States, the United Kingdom, and China, covering 2004 to 2019. The trajectory of BRI was determined using latent class growth mixed models, and the relationship between BRI trajectory and CVD risk was evaluated using Cox models.
Results
Three longitudinal BRI trajectories were characterized: inverse-U (7.2%), low-increasing (44.4%), and middle-increasing (48.4%). The risk of CVD in the middle-increasing group and the inverse-U group was 1.25 times (95% CI: 1.12–1.35) and 1.86 times (1.53–2.36) higher than that in the low-increasing group, respectively. The historical maximum BRI, area under the curve, and time-weighted BRI all showed a nonlinear risk of CVD in the dose–response relationship (p < 0.05). The effect of BRI growth rate on CVD decreased with age.
Conclusions
The BRI trajectories were significantly associated with CVD risk, independent of baseline BRI and BMI. This emphasizes the long-term and persistent effects of visceral fat accumulation and may provide a reference for personalized CVD risk assessment and early impact.
{"title":"Association of Longitudinal Trajectory of Body Roundness Index With CVD Risk: Evidence From a Multicohort Study","authors":"Xingfang Wang, Jianhua Gu, Shuo Wu, Ping Fu, Jiqing Li","doi":"10.1002/oby.70038","DOIUrl":"10.1002/oby.70038","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to characterize the longitudinal trajectory of the body roundness index (BRI) in a multinational cohort and to investigate its association with cardiovascular disease (CVD) events.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We pooled individual-level data from three prospective cohort studies across the United States, the United Kingdom, and China, covering 2004 to 2019. The trajectory of BRI was determined using latent class growth mixed models, and the relationship between BRI trajectory and CVD risk was evaluated using Cox models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Three longitudinal BRI trajectories were characterized: inverse-U (7.2%), low-increasing (44.4%), and middle-increasing (48.4%). The risk of CVD in the middle-increasing group and the inverse-U group was 1.25 times (95% CI: 1.12–1.35) and 1.86 times (1.53–2.36) higher than that in the low-increasing group, respectively. The historical maximum BRI, area under the curve, and time-weighted BRI all showed a nonlinear risk of CVD in the dose–response relationship (<i>p</i> < 0.05). The effect of BRI growth rate on CVD decreased with age.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The BRI trajectories were significantly associated with CVD risk, independent of baseline BRI and BMI. This emphasizes the long-term and persistent effects of visceral fat accumulation and may provide a reference for personalized CVD risk assessment and early impact.</p>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":"33 12","pages":"2387-2397"},"PeriodicalIF":4.7,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145208905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bernard Tang, Suresh Anand Sadananthan, Delicia Shu Qin Ooi, Natarajan Padmapriya, Mya Thway Tint, Elaine Kwang-Hsia Tham, Daniel Yam Thiam Goh, Birit F. P. Broekman, Joshua J. Gooley, Oon Hoe Teoh, Yap-Seng Chong, Peter D. Gluckman, Fabian Yap, Johan G. Eriksson, S. Sendhil Velan, Falk Müller-Riemenschneider, Yung Seng Lee, Navin Michael, Shirong Cai
Objective
This study aimed to examine sex-stratified associations between meeting recommended sleep duration and adiposity in 10-year-old children.
Methods
Using the GUSTO cohort (51% boys, 10.2 ± 0.2 years), we evaluated the associations of meeting sleep duration recommendations (total daily sleep duration of ≥ 9 h, caregiver-reported and actigraphy) throughout the week with obesity and BMI z-scores (N = 638), glycoprotein acetyls (n = 436), fat mass measured by quantitative magnetic resonance (n = 528), and abdominal adipose tissue volumes measured by magnetic resonance imaging (N = 377). Multivariable linear and logistic regressions were used, adjusted for ethnicity and maternal education.
Results
Boys, but not girls, whose caregiver-reported sleep duration met recommendations throughout the entire week had a lower risk of obesity (BMIz > 2.0) (OR = 0.49, 95% CI 0.27–0.87), BMIz (0.34 ± 0.16 vs. 0.98 ± 0.12) (p = 0.001), glycoprotein acetyls levels (0.65 ± 0.01 mmol/L vs. 0.70 ± 0.01 mmol/L) (p < 0.001), total fat mass (8.77 ± 0.69 kg vs. 11.31 ± 0.51 kg) (p = 0.002), and deep subcutaneous (492 ± 86 mL vs. 729 ± 56 mL) (p = 0.014), superficial subcutaneous (651 ± 85 mL vs. 888 ± 55 mL) (p = 0.013), and visceral (415 ± 51 mL vs. 557 ± 33 mL) (p = 0.013) adipose tissue volumes.
Conclusions
Interventions to help children attain recommended sleep duration for weekdays and weekends may reduce abdominal and total adiposity, especially in boys.
目的：本研究旨在探讨符合推荐睡眠时间与10岁儿童肥胖之间的性别分层关系。方法：使用GUSTO队列（51%的男孩，10.2±0.2岁），我们评估了一周内满足睡眠时间建议（每日总睡眠时间≥9小时，照顾者报告和活动记录）与肥胖和BMI z-评分（N = 638）、糖蛋白乙酰（N = 436）、定量磁共振测量的脂肪量（N = 528）和磁共振成像测量的腹部脂肪组织体积（N = 377）的关系。采用多变量线性和逻辑回归，并根据种族和母亲教育程度进行调整。结果：男孩，而不是女孩，其看护人报告的睡眠时间在整个星期符合建议的肥胖风险较低（BMIz bbb2.0） （OR = 0.49, 95% CI 0.27-0.87）， BMIz(0.34±0.16 vs. 0.98±0.12)(p = 0.001)，糖蛋白乙酰水平（0.65±0.01 mmol/L vs. 0.70±0.01 mmol/L） (p结论：帮助儿童达到推荐的工作日和周末睡眠时间的干预措施可以减少腹部和总体肥胖，尤其是男孩。
{"title":"Meeting Sleep Duration Recommendations is Associated With Lower Abdominal Adipose Tissue in 10-Year-Old Boys","authors":"Bernard Tang, Suresh Anand Sadananthan, Delicia Shu Qin Ooi, Natarajan Padmapriya, Mya Thway Tint, Elaine Kwang-Hsia Tham, Daniel Yam Thiam Goh, Birit F. P. Broekman, Joshua J. Gooley, Oon Hoe Teoh, Yap-Seng Chong, Peter D. Gluckman, Fabian Yap, Johan G. Eriksson, S. Sendhil Velan, Falk Müller-Riemenschneider, Yung Seng Lee, Navin Michael, Shirong Cai","doi":"10.1002/oby.70026","DOIUrl":"10.1002/oby.70026","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to examine sex-stratified associations between meeting recommended sleep duration and adiposity in 10-year-old children.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using the GUSTO cohort (51% boys, 10.2 ± 0.2 years), we evaluated the associations of meeting sleep duration recommendations (total daily sleep duration of ≥ 9 h, caregiver-reported and actigraphy) throughout the week with obesity and BMI <i>z</i>-scores (<i>N</i> = 638), glycoprotein acetyls (<i>n</i> = 436), fat mass measured by quantitative magnetic resonance (<i>n</i> = 528), and abdominal adipose tissue volumes measured by magnetic resonance imaging (<i>N</i> = 377). Multivariable linear and logistic regressions were used, adjusted for ethnicity and maternal education.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Boys, but not girls, whose caregiver-reported sleep duration met recommendations throughout the entire week had a lower risk of obesity (BMIz > 2.0) (OR = 0.49, 95% CI 0.27–0.87), BMIz (0.34 ± 0.16 vs. 0.98 ± 0.12) (<i>p</i> = 0.001), glycoprotein acetyls levels (0.65 ± 0.01 mmol/L vs. 0.70 ± 0.01 mmol/L) (<i>p</i> < 0.001), total fat mass (8.77 ± 0.69 kg vs. 11.31 ± 0.51 kg) (<i>p</i> = 0.002), and deep subcutaneous (492 ± 86 mL vs. 729 ± 56 mL) (<i>p</i> = 0.014), superficial subcutaneous (651 ± 85 mL vs. 888 ± 55 mL) (<i>p</i> = 0.013), and visceral (415 ± 51 mL vs. 557 ± 33 mL) (<i>p</i> = 0.013) adipose tissue volumes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Interventions to help children attain recommended sleep duration for weekdays and weekends may reduce abdominal and total adiposity, especially in boys.</p>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":"33 12","pages":"2345-2354"},"PeriodicalIF":4.7,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Moein Minbashi Moeini, Olivier Lavoie, Alexandre Caron, Kevin W. Williams, Natalie J. Michael
Objective
Topiramate is a medication used off-label, or in combination with phentermine, for the management of obesity. However, its mechanism of action remains elusive. As many obesity medications target the brain, we aimed to determine if topiramate influences the activity of hypothalamic melanocortin neurons known to regulate energy balance.
Methods
Transgenic mice expressing a fluorescent protein in either “orexigenic” neuropeptide Y/agouti-related peptide (NPY/AgRP) or “anorexigenic” pro-opiomelanocortin (POMC) neurons were used to perform whole-cell patch clamp electrophysiology experiments in the arcuate nucleus (ARC) of the hypothalamus.
Results
Topiramate (1 μM) strongly inhibited NPY/AgRP neuron electrical excitability. Despite topiramate's well-known actions at GABAA receptors, we demonstrate that the topiramate-induced inhibition of NPY/AgRP neurons does not involve GABAA receptors. The effects of topiramate on NPY/AgRP neurons were suppressed by inhibitors of synaptic transmission and after blockade of GABAB receptors or potassium channels. In contrast, topiramate had negligible influence on the activity of POMC neurons.
Conclusions
This study is the first demonstration that topiramate strongly inhibits the activity of ARC NPY/AgRP neurons and suggests that enhanced GABAergic tone to these neurons mediates this effect. The ability of topiramate to inhibit the orexigenic NPY/AgRP neurons may underlie some of its weight-lowering properties.
{"title":"Topiramate Enhances GABAergic Tone to Orexigenic Neuropeptide Y/Agouti-Related Peptide (NPY/AgRP) Neurons","authors":"Moein Minbashi Moeini, Olivier Lavoie, Alexandre Caron, Kevin W. Williams, Natalie J. Michael","doi":"10.1002/oby.70051","DOIUrl":"10.1002/oby.70051","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Topiramate is a medication used off-label, or in combination with phentermine, for the management of obesity. However, its mechanism of action remains elusive. As many obesity medications target the brain, we aimed to determine if topiramate influences the activity of hypothalamic melanocortin neurons known to regulate energy balance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Transgenic mice expressing a fluorescent protein in either “orexigenic” neuropeptide Y/agouti-related peptide (NPY/AgRP) or “anorexigenic” pro-opiomelanocortin (POMC) neurons were used to perform whole-cell patch clamp electrophysiology experiments in the arcuate nucleus (ARC) of the hypothalamus.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Topiramate (1 μM) strongly inhibited NPY/AgRP neuron electrical excitability. Despite topiramate's well-known actions at GABA<sub>A</sub> receptors, we demonstrate that the topiramate-induced inhibition of NPY/AgRP neurons does not involve GABA<sub>A</sub> receptors. The effects of topiramate on NPY/AgRP neurons were suppressed by inhibitors of synaptic transmission and after blockade of GABA<sub>B</sub> receptors or potassium channels. In contrast, topiramate had negligible influence on the activity of POMC neurons.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study is the first demonstration that topiramate strongly inhibits the activity of ARC NPY/AgRP neurons and suggests that enhanced GABAergic tone to these neurons mediates this effect. The ability of topiramate to inhibit the orexigenic NPY/AgRP neurons may underlie some of its weight-lowering properties.</p>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":"34 1","pages":"175-187"},"PeriodicalIF":4.7,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12724042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nuno R. Zilhao, Jie Zhang, Dorret I. Boomsma, Thorkild I. A. Sørensen, Christina C. Dahm
Objective
The relation between genetically predicted BMI (gBMI) and actual BMI may have health effects. This study examines the relationship between deviations from gBMI and all-cause mortality in 208,146 UK Biobank participants.
Methods
We derived gBMI from polygenic risk scores, with deviations calculated as the difference between observed and predicted BMI. Cox proportional hazards models are adjusted for confounders and current BMI.
Results
Downward deviations (> 2 SD below gBMI) were associated with significantly increased mortality (HR: 1.25, 95% CI: 1.01–1.55), whereas upward deviations (> 2 SD above) showed no significant effect (HR: 1.10, 95% CI: 0.93–1.29). The mortality exhibited the known nonlinear J-shaped association with observed BMI, here lowest at BMI ~22 kg/m2, but this nadir varied by genetic predisposition; thus, for individuals with high gBMI, lowest mortality occurred at higher observed BMI (24–26 kg/m2), while those with low or medium gBMI showed sharper increases in mortality at higher BMI.
Conclusions
These findings highlight the possible importance of aligning current BMI to genetic predisposition, and future research should examine BMI deviations and their long-term health effects. This perspective may inform personalized obesity management strategies to optimize health outcomes.
{"title":"Deviation From Genetically Predicted BMI and All-Cause Mortality: A Cohort Study in the UK Biobank","authors":"Nuno R. Zilhao, Jie Zhang, Dorret I. Boomsma, Thorkild I. A. Sørensen, Christina C. Dahm","doi":"10.1002/oby.70042","DOIUrl":"10.1002/oby.70042","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The relation between genetically predicted BMI (gBMI) and actual BMI may have health effects. This study examines the relationship between deviations from gBMI and all-cause mortality in 208,146 UK Biobank participants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We derived gBMI from polygenic risk scores, with deviations calculated as the difference between observed and predicted BMI. Cox proportional hazards models are adjusted for confounders and current BMI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Downward deviations (> 2 SD below gBMI) were associated with significantly increased mortality (HR: 1.25, 95% CI: 1.01–1.55), whereas upward deviations (> 2 SD above) showed no significant effect (HR: 1.10, 95% CI: 0.93–1.29). The mortality exhibited the known nonlinear J-shaped association with observed BMI, here lowest at BMI ~22 kg/m<sup>2</sup>, but this nadir varied by genetic predisposition; thus, for individuals with high gBMI, lowest mortality occurred at higher observed BMI (24–26 kg/m<sup>2</sup>), while those with low or medium gBMI showed sharper increases in mortality at higher BMI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings highlight the possible importance of aligning current BMI to genetic predisposition, and future research should examine BMI deviations and their long-term health effects. This perspective may inform personalized obesity management strategies to optimize health outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":"34 1","pages":"228-236"},"PeriodicalIF":4.7,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12724034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145208887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hamlet Gasoyan, W. Scott Butsch, Nicholas J. Casacchia, Rebecca Schulte, Victoria Criswell, Jacqueline Fox, Holly Renner, Phuc Le, Jordan Alpert, Michael B. Rothberg
Objective
This study aimed to characterize the reasons for treatment discontinuation with injectable semaglutide or tirzepatide for obesity in regular clinical practice.
Methods
This cross-sectional study used electronic health record data between January 2022 and December 2024 from a single integrated health system in Ohio and Florida. The primary reason for treatment discontinuation was examined in a randomly selected sample of adults with overweight or obesity and without type 2 diabetes who initiated injectable semaglutide or tirzepatide and discontinued treatment within the first year.
Results
We randomly selected 288 patients; 145 received semaglutide and 143 tirzepatide. Overall, 137 patients (47.6%) discontinued their medication due to cost or insurance-related issues, 42 (14.6%) due to inability to tolerate the side effects, 34 (11.8%) as they were unable to fill the medication due to shortages, 7 (2.4%) as they switched to a compounded medication, and 5 (1.7%) due to unsatisfactory weight loss; 31 (10.8%) discontinued for other reasons, and for 32 (11.1%) patients the discontinuation reason was not specified in the electronic health record.
Conclusions
High cost or insurance-related issues are the most common reasons for treatment discontinuation with semaglutide or tirzepatide for obesity. Our findings highlight the need for policies to address cost and could inform discussions between healthcare providers and patients concerning cost and side effects.
{"title":"Reasons for Discontinuation of Obesity Pharmacotherapy With Semaglutide or Tirzepatide in Clinical Practice","authors":"Hamlet Gasoyan, W. Scott Butsch, Nicholas J. Casacchia, Rebecca Schulte, Victoria Criswell, Jacqueline Fox, Holly Renner, Phuc Le, Jordan Alpert, Michael B. Rothberg","doi":"10.1002/oby.70058","DOIUrl":"10.1002/oby.70058","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to characterize the reasons for treatment discontinuation with injectable semaglutide or tirzepatide for obesity in regular clinical practice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This cross-sectional study used electronic health record data between January 2022 and December 2024 from a single integrated health system in Ohio and Florida. The primary reason for treatment discontinuation was examined in a randomly selected sample of adults with overweight or obesity and without type 2 diabetes who initiated injectable semaglutide or tirzepatide and discontinued treatment within the first year.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We randomly selected 288 patients; 145 received semaglutide and 143 tirzepatide. Overall, 137 patients (47.6%) discontinued their medication due to cost or insurance-related issues, 42 (14.6%) due to inability to tolerate the side effects, 34 (11.8%) as they were unable to fill the medication due to shortages, 7 (2.4%) as they switched to a compounded medication, and 5 (1.7%) due to unsatisfactory weight loss; 31 (10.8%) discontinued for other reasons, and for 32 (11.1%) patients the discontinuation reason was not specified in the electronic health record.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>High cost or insurance-related issues are the most common reasons for treatment discontinuation with semaglutide or tirzepatide for obesity. Our findings highlight the need for policies to address cost and could inform discussions between healthcare providers and patients concerning cost and side effects.</p>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":"33 12","pages":"2296-2303"},"PeriodicalIF":4.7,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/oby.70058","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Altayeb Ahmed, Afreen Naz, Marjola Thanaj, Elena P. Sorokin, Brandon Whitcher, Jimmy D. Bell, E. Louise Thomas, Madeleine Cule, Hanieh Yaghootkar
Objective
Fatty acids in adipose tissue are key structural and metabolic regulators of cardiometabolic health, but the genetic architecture governing depot-specific composition in subcutaneous (SAT) and visceral adipose tissue (VAT) is not well defined.
Methods
We used MRI-derived estimates of fatty acid composition in SAT and VAT from 33,583 UK Biobank participants to perform genome-wide association studies. Functional annotation, fine mapping, colocalization, and expression QTL analyses were conducted to prioritize likely causal variants and explore mechanisms.
Results
We identified six loci associated with adipose tissue fatty acid composition, including both shared (PKD2L1, INSIG1) and depot-specific associations (LEKR1 and KLF14 for SAT; CDCA2 for VAT). The strongest association, rs603424-G (near PKD2L1), was linked to higher monounsaturated and polyunsaturated fatty acids, lower saturated fatty acids, and increased SCD1 expression in SAT and VAT, suggesting a role in desaturation and lipid remodeling. Several loci were linked to cardiometabolic outcomes including type 2 diabetes, hypertension, and cholelithiasis, with functional evidence supporting gene–diet interactions at the PKD2L1 locus.
Conclusions
Our findings uncover genetic determinants of human adipose tissue fatty acid composition, highlight depot-specific regulation, and point to SCD1 as a potential metabolic regulator. These results deepen understanding of lipid metabolism and its links to cardiometabolic risk.
{"title":"Genetic Determinants of Fatty Acid Composition in Subcutaneous and Visceral Adipose Tissue","authors":"Altayeb Ahmed, Afreen Naz, Marjola Thanaj, Elena P. Sorokin, Brandon Whitcher, Jimmy D. Bell, E. Louise Thomas, Madeleine Cule, Hanieh Yaghootkar","doi":"10.1002/oby.70045","DOIUrl":"10.1002/oby.70045","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Fatty acids in adipose tissue are key structural and metabolic regulators of cardiometabolic health, but the genetic architecture governing depot-specific composition in subcutaneous (SAT) and visceral adipose tissue (VAT) is not well defined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used MRI-derived estimates of fatty acid composition in SAT and VAT from 33,583 UK Biobank participants to perform genome-wide association studies. Functional annotation, fine mapping, colocalization, and expression QTL analyses were conducted to prioritize likely causal variants and explore mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified six loci associated with adipose tissue fatty acid composition, including both shared (<i>PKD2L1</i>, <i>INSIG1</i>) and depot-specific associations (<i>LEKR1</i> and <i>KLF14</i> for SAT; <i>CDCA2</i> for VAT). The strongest association, rs603424-G (near <i>PKD2L1</i>), was linked to higher monounsaturated and polyunsaturated fatty acids, lower saturated fatty acids, and increased <i>SCD1</i> expression in SAT and VAT, suggesting a role in desaturation and lipid remodeling. Several loci were linked to cardiometabolic outcomes including type 2 diabetes, hypertension, and cholelithiasis, with functional evidence supporting gene–diet interactions at the <i>PKD2L1</i> locus.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings uncover genetic determinants of human adipose tissue fatty acid composition, highlight depot-specific regulation, and point to <i>SCD1</i> as a potential metabolic regulator. These results deepen understanding of lipid metabolism and its links to cardiometabolic risk.</p>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":"33 12","pages":"2406-2415"},"PeriodicalIF":4.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/oby.70045","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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