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1,25‑Dihydroxyvitamin D3 mitigates the adipogenesis induced by bisphenol A in 3T3-L1 and hAMSC through miR-27-3p regulation 1,25-二羟维生素 D3 通过调控 miR-27-3p 减轻双酚 A 诱导的 3T3-L1 和 hAMSC 脂肪生成
IF 4.9 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-09-10 DOI: 10.1038/s41366-024-01629-w
Donatella Paola Provvisiero, Mariarosaria Negri, Feliciana Amatrudo, Roberta Patalano, Tatiana Montò, Cristina de Angelis, Chiara Graziadio, Gabriella Pugliese, Giulia de Alteriis, Annamaria Colao, Rosario Pivonello, Silvia Savastano, Claudia Pivonello

Purpose

Endocrine-disrupting compounds, including bisphenol A (BPA), may promote obesity influencing basal metabolic rate and shifting metabolism towards energy storage. The role of 1,25‑Dihydroxyvitamin D3 (VitD) in counteracting adipogenesis is still a matter of debate. Thus, the current study aims to investigate whether and how VitD exposure during adipogenesis could prevent the pro-adipogenic effect of BPA in two adipocyte models, mouse 3T3-L1 cell line and human adipose-derived mesenchymal stem cells (hAMSC).

Methods

3T3-L1, mouse pre-adipocytes and human adipose-derived mesenchymal stem cells (hAMSC) were treated with VitD (10−7 M) and BPA (10−8 M and 10−9 M), alone or in combination, throughout the differentiation in mature adipocytes. Cellular lipid droplet accumulation was assessed by Oil Red O staining, mRNA and protein expression of key adipogenic markers, transcription factors, and cytokines were investigated by RT-qPCR and WB, respectively. miRNAs involved in the regulation of adipogenic transcription factors were evaluated by RT-qPCR, and highly potent steric-blocking oligonucleotides (miRNA inhibitors) were used to modulate miRNAs expression.

Results

Pre-adipocytes express VitD receptor (VDR) in basal condition, but during the differentiation process VDR expression reduces if not stimulated by the ligand. VitD significantly decreases lipid accumulation, with a consequent reduction in adipogenic marker expression, and counteracts the pro-adipogenic effect of BPA in 3T3-L1 and hAMSC during differentiation. This effect is associated to the increased expression of miR-27a-3p and miR-27b-3p. The blocking of miR-27a-3p and miR-27b-3p through miRNA inhibitors prevents the anti-adipogenic effect of VitD in both cell models.

Conclusions

These results suggest that in cultured 3T3-L1 and hAMSC VitD induces an anti-adipogenic effect and prevents BPA pro-adipogenic effect by triggering at least in part epigenetic mechanisms involving miR-27-3p.

目的包括双酚 A(BPA)在内的干扰内分泌的化合物可能会促进肥胖,影响基础代谢率并使新陈代谢转向能量储存。1,25-二羟维生素 D3(VitD)在抑制脂肪生成方面的作用仍存在争议。因此,本研究旨在探讨在两种脂肪细胞模型(小鼠 3T3-L1 细胞系和人脂肪间充质干细胞(hAMSC))中,脂肪生成过程中暴露于 VitD 是否以及如何阻止双酚 A 的促脂肪生成效应。方法在成熟脂肪细胞的整个分化过程中,单独或联合使用 VitD(10-7 M)和 BPA(10-8 M 和 10-9 M)处理 3T3-L1、小鼠前脂肪细胞和人脂肪间充质干细胞(hAMSC)。用油红 O 染色法评估细胞脂滴的积累,用 RT-qPCR 和 WB 分别检测关键脂肪生成标志物、转录因子和细胞因子的 mRNA 和蛋白表达。结果 前期脂肪细胞在基础状态下会表达 VitD 受体(VDR),但在分化过程中,如果没有配体的刺激,VDR 的表达会降低。在 3T3-L1 和 hAMSC 的分化过程中,VitD 能明显降低脂质积累,从而减少脂肪生成标志物的表达,并抵消双酚 A 的促脂肪生成作用。这种效应与 miR-27a-3p 和 miR-27b-3p 的表达增加有关。结论:这些结果表明,在培养的 3T3-L1 和 hAMSC 中,VitD 通过触发至少部分涉及 miR-27-3p 的表观遗传学机制,诱导了抗致脂作用,并阻止了 BPA 的促致脂作用。
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引用次数: 0
Alcohol use disorders after bariatric surgery: a study using linked health claims and survey data. 减肥手术后的酒精使用障碍:一项使用关联健康索赔和调查数据进行的研究。
IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-09-06 DOI: 10.1038/s41366-024-01606-3
Oliver Riedel, Malte Braitmaier, Mark Dankhoff, Ulrike Haug, Melanie Klein, Wiebke Zachariassen, Jana Hoyer

Background: Previous studies have repeatedly reported alcohol use disorders (AUDs) in patients after bariatric surgery (BS). This research field can benefit from studies combining health claims data with survey data.

Methods: Based on a combined retrospective cohort and cross-sectional study, 2151 patients with BS identified in a large health claims database received a questionnaire, by which we assessed the presence of AUDs based on a validated instrument (AUDIT) as well as by ICD-10 codes from the health claims data. We described patients with vs. without AUDs regarding sex, time since surgery, satisfaction with weight loss and health care resource utilization (HCRU).

Results: The majority of patients were female (80.7%) with a median time since surgery of 6 years (Interquartile range: 4-9 years). For the majority of patients, the bariatric intervention was either a RYGB-Bypass (50%) or sleeve gastrectomy (43%). Overall, 3% had at least one AUD diagnosis code in the claims data (men: 5.5%, women: 2.5%). Among men, 43.6% of diagnoses were coded after but not before the surgery (women: 52%). According to AUDIT (completed by 1496 patients), 9.4% of all patients showed at least hazardous/harmful alcohol consumption. Higher scores were associated with sex of the person, longer time since surgery, dissatisfaction with the weight loss and higher HCRU, with contradicting results regarding psychotherapeutic care.

Conclusions: The proportion with AUDs in the study population gives rise to concern as alcohol consumption should be restricted after BS. The results suggest the necessity for close monitoring and post-surgical care.

背景:以前的研究曾多次报告过减肥手术(BS)后患者的酒精使用障碍(AUDs)。将健康索赔数据与调查数据相结合的研究将使这一研究领域受益匪浅:基于一项回顾性队列研究和横断面研究,我们对大型健康索赔数据库中的 2151 名减肥手术患者进行了问卷调查,根据有效工具(AUDIT)和健康索赔数据中的 ICD-10 编码评估了患者是否存在 AUDs。我们从性别、手术后时间、对减肥的满意度和医疗资源利用率(HCRU)等方面对有和无 AUDs 的患者进行了描述:大多数患者为女性(80.7%),手术后的中位时间为 6 年(四分位距:4-9 年)。大多数患者的减肥手术是 RYGB-旁路术(50%)或袖状胃切除术(43%)。总体而言,3% 的患者在索赔数据中至少有一个 AUD 诊断代码(男性:5.5%,女性:2.5%)。在男性中,43.6% 的诊断代码是在手术后而非手术前输入的(女性:52%)。根据 AUDIT(由 1496 名患者填写),9.4% 的患者至少有危险/有害饮酒行为。得分较高与患者性别、手术后时间较长、对体重减轻不满意以及HCRU较高有关,而心理治疗方面的结果则相互矛盾:结论:研究人群中的酒精成瘾者比例令人担忧,因为 BS 术后应限制饮酒。研究结果表明,有必要对患者进行密切监测和术后护理。
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引用次数: 0
Associations of circulating total p-cresylsulfate and indoxyl sulfate concentrations with central obesity in patients with stable coronary artery disease: sex-specific insights. 稳定型冠心病患者循环中总对甲酚硫酸盐和吲哚硫酸盐浓度与中心性肥胖的关系:性别特异性见解。
IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-09-05 DOI: 10.1038/s41366-024-01624-1
Thung-Lip Lee, Chin-Feng Hsuan, Chia-Chang Hsu, Ching-Ting Wei, Chao-Ping Wang, Yung-Chuan Lu, Wei-Hua Tang, Nan-Han Lu, Fu-Mei Chung, Yau-Jiunn Lee, I-Ting Tsai

Background/aims: Elevated systemic inflammation, common in obesity, increases cardiovascular disease risk. Obesity is linked to a pro-inflammatory gut microbiota that releases uremic toxins like p-cresylsulfate (PCS) and indoxyl sulfate (IS), which are implicated in coronary atherosclerosis, insulin resistance, and chronic kidney disease. This study examines the relationship between total PCS and IS levels and central obesity in patients with stable coronary artery disease (CAD).

Methods: A cross-sectional study was conducted on 373 consecutive patients with stable CAD from a single center. Serum levels of total PCS and IS were measured using an Ultra Performance LC System. Central obesity was evaluated using a body shape index (ABSI) and conicity index (CI). Six obesity-related proteins were also analyzed. Structural equation modeling (SEM) assessed direct and indirect effects of total PCS, IS, and the six obesity-related proteins on central obesity.

Results: Significant positive correlations were found between total PCS and IS with waist-to-hip ratio (WHR) (r = 0.174, p = 0.005 for total PCS; r = 0.144, p = 0.021 for IS), CI (r = 0.273, p < 0.0001 for total PCS; r = 0.260, p < 0.0001 for IS), and ABSI (r = 0.297, p < 0.0001 for total PCS; r = 0.285, p < 0.0001 for IS) in male patients, but not in female patients. Multivariate analysis showed higher odds ratios (ORs) for elevated CI (OR = 3.18, 95% CI: 1.54-6.75, p = 0.002) and ABSI (OR = 3.28, 95% CI: 1.54-7.24, p = 0.002) in patients with high PCS levels, and elevated CI (OR = 2.30, 95% CI: 1.15-4.66, p = 0.018) and ABSI (OR = 2.22, 95% CI: 1.07-4.72, p = 0.033) in those with high IS levels, compared to those with low toxin levels. SEM analysis indicated that total PCS and IS directly impacted central obesity indices and indirectly influenced central adiposity measures like WHR through high sensitivity C-reactive protein (hs-CRP) (β = 0.252, p < 0.001).

Conclusions: Circulating total PCS and IS contribute to central obesity in male patients with stable CAD, partially mediated by hs-CRP.

背景/目的:肥胖常见的全身性炎症会增加心血管疾病风险。肥胖与促炎性肠道微生物群有关,这种微生物群会释放尿毒症毒素,如对甲酚硫酸盐(PCS)和吲哚硫酸盐(IS),而这些毒素与冠状动脉粥样硬化、胰岛素抵抗和慢性肾脏疾病有关。本研究探讨了稳定型冠状动脉疾病(CAD)患者的总 PCS 和 IS 水平与中心性肥胖之间的关系:方法:一项横断面研究针对一个中心的 373 名连续稳定型冠状动脉疾病患者。使用超高效液相色谱系统测量血清总PCS和IS水平。中心性肥胖采用体形指数(ABSI)和圆锥指数(CI)进行评估。此外,还分析了六种与肥胖相关的蛋白质。结构方程模型(SEM)评估了总 PCS、IS 和六种肥胖相关蛋白质对中心性肥胖的直接和间接影响:结果:发现总 PCS 和 IS 与腰臀比(WHR)(总 PCS 的 r = 0.174,p = 0.005;IS 的 r = 0.144,p = 0.021)、CI(r = 0.273,p 结论:总 PCS 和 IS 与腰臀比(WHR)和 CI 之间存在显著的正相关:血液循环中的总 PCS 和 IS 会导致患有稳定型冠状动脉粥样硬化症的男性患者出现中心性肥胖,部分原因在于 hs-CRP。
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引用次数: 0
Recruitment and retention of participants with obesity into a longitudinal birth cohort: the Breastfeeding and Early Child Health (BEACH) study 纵向出生队列中肥胖症参与者的招募和保留:母乳喂养和早期儿童健康(BEACH)研究
IF 4.9 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-09-05 DOI: 10.1038/s41366-024-01625-0
Faith Anne N. Heeren, Michele Himadi, Elizabeth Flood-Grady, Ke Xu, Matthew Shane Loop, Magda Francois, Adetola F. Louis-Jacques, Lindsay Thompson, Michelle I. Cardel, Yasmine Gillespie, Lewis DeCicco, Dominick J. Lemas

Background

The study aimed to evaluate how maternal pre-pregnant body mass index (BMI) impacts participant recruitment and retention.

Methods

Participants were enrolled in a longitudinal study between 30 and 36 weeks of pregnancy as having normal weight (pre-pregnant BMI ≥ 18.5 and <25 kg/m2) or obesity (pre-pregnant BMI ≥ 30.0 kg/m2). Recruitment channels included Facebook, email, newspaper, phone calls, radio advertisements, flyers, and word-of-mouth. The stages of recruitment included eligibility, consent, and completion. Pearson’s chi-square tests were used to evaluate the relationship between BMI and enrollment outcomes.

Results

Recruitment yielded 2770 total prospective participants. After screening, 141 individuals were eligible, 83 consented, and 60 completed the study. Facebook was the most successful method for identifying eligible pregnant patients with obesity, while a higher percentage of participants recruited through word-of-mouth and flyers consented to the study. Pre-pregnant BMI was significantly associated with the stage of recruitment completed by the participant (p = 0.04), whereby individuals eligible for the study with obesity were less likely to consent and complete study visits.

Conclusion

We demonstrated that maternal obesity was significantly associated with enrollment outcomes in a longitudinal birth cohort study. This study showed that pre-pregnancy BMI influenced study participation. Therefore, tailored recruitment strategies to enhance the recruitment and enrollment of individuals with obesity in maternal-infant health research may be necessary.

背景该研究旨在评估孕产妇孕前体重指数(BMI)对参与者招募和保留的影响。方法参与者在怀孕 30 到 36 周之间被纳入一项纵向研究,体重正常(孕前体重指数≥18.5 和 25 kg/m2)或肥胖(孕前体重指数≥30.0 kg/m2)。招募渠道包括 Facebook、电子邮件、报纸、电话、广播广告、传单和口碑。招募阶段包括资格审查、同意和完成。皮尔逊卡方检验用于评估体重指数与招募结果之间的关系。经过筛选,141 人符合条件,83 人同意,60 人完成了研究。Facebook 是识别符合条件的肥胖症孕妇患者最成功的方法,而通过口口相传和传单招募的参与者中同意参加研究的比例较高。孕前体重指数与参与者完成的招募阶段显著相关(p = 0.04),因此符合研究条件的肥胖者不太可能同意并完成研究访问。这项研究表明,孕前体重指数会影响研究的参与度。因此,在母婴健康研究中,可能有必要采取有针对性的招募策略,以提高肥胖症患者的招募和注册率。
{"title":"Recruitment and retention of participants with obesity into a longitudinal birth cohort: the Breastfeeding and Early Child Health (BEACH) study","authors":"Faith Anne N. Heeren, Michele Himadi, Elizabeth Flood-Grady, Ke Xu, Matthew Shane Loop, Magda Francois, Adetola F. Louis-Jacques, Lindsay Thompson, Michelle I. Cardel, Yasmine Gillespie, Lewis DeCicco, Dominick J. Lemas","doi":"10.1038/s41366-024-01625-0","DOIUrl":"https://doi.org/10.1038/s41366-024-01625-0","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>The study aimed to evaluate how maternal pre-pregnant body mass index (BMI) impacts participant recruitment and retention.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Participants were enrolled in a longitudinal study between 30 and 36 weeks of pregnancy as having normal weight (pre-pregnant BMI ≥ 18.5 and &lt;25 kg/m<sup>2</sup>) or obesity (pre-pregnant BMI ≥ 30.0 kg/m<sup>2</sup>). Recruitment channels included Facebook, email, newspaper, phone calls, radio advertisements, flyers, and word-of-mouth. The stages of recruitment included eligibility, consent, and completion. Pearson’s chi-square tests were used to evaluate the relationship between BMI and enrollment outcomes.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Recruitment yielded 2770 total prospective participants. After screening, 141 individuals were eligible, 83 consented, and 60 completed the study. Facebook was the most successful method for identifying eligible pregnant patients with obesity, while a higher percentage of participants recruited through word-of-mouth and flyers consented to the study. Pre-pregnant BMI was significantly associated with the stage of recruitment completed by the participant (<i>p</i> = 0.04), whereby individuals eligible for the study with obesity were less likely to consent and complete study visits.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>We demonstrated that maternal obesity was significantly associated with enrollment outcomes in a longitudinal birth cohort study. This study showed that pre-pregnancy BMI influenced study participation. Therefore, tailored recruitment strategies to enhance the recruitment and enrollment of individuals with obesity in maternal-infant health research may be necessary.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142206329","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}
引用次数: 0
Impact of aging on long-term cardiac outcomes of true-lumen recanalized chronic total occlusions in patients with overweight/obesity. 老龄化对超重/肥胖患者真腔再通慢性全闭塞长期心脏预后的影响
IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-09-04 DOI: 10.1038/s41366-024-01623-2
Jen-Fang Cheng, Chien-Lin Lee, Jiunn-Yang Chiang, Shih-Chi Liu, Chi-Hung Huang, Jun-Ting Liou, Chi-Jen Chang, Cheng-Ting Tsai, Chia-Ti Tsai, Yi-Chih Wang, Juey-Jen Hwang

Background: Obesity paradox addressing all-cause mortality has been described in several chronic total occlusion (CTO) studies. However, the impact of aging on long-term cardiac events in patients with overweight and obesity with CTO recanalization were less studied.

Methods: A total of 458 patients (64.4 ± 11.3 years, 403 male) with CTO interventions were enrolled. The overweight/obesity group included 311 patients with body mass index (BMI) ≧24 kg/m2 and the non-obesity group included 147. With a median follow-up of 40.0 (17.9-61.4) months, 422 patients with successful true-lumen recanalization were further assessed for target lesion failure [TLF: cardiac death, target vessel myocardial infarction (TVMI), target lesion revascularization (TLR)].

Results: At follow-up, the rates of cardiac death, TVMI, TLR, TLF, and stent thrombosis were 1.9%, 1.9%, 9.2%, 10.7%, and 0.5%, respectively. The TVMI-free survival was borderline better (p = 0.067 by log-rank test) in overweight/obesity than non-obesity group. Among patients <65 years of age, the TVMI-free survival was significantly better in the overweight/obesity group (p = 0.013 compared to non-obesity group by log-rank test). In multivariate Cox regression model, the non-obesity patients younger than 65 years were at a higher risk of TVMI, not only among those <65 years of age (hazard ratio = 11.0, 95% CI = 1.1-106.0) but also among the whole patients (hazard ratio=6.9, 95% CI = 1.4-35.1) with successful CTO recanalization.

Conclusions: For those with true-lumen recanalized CTO, the higher risk of TVMI after successful recanalization was rather evident in patients <65 years of age and without overweight/obesity, suggesting that aging might attenuate prognostic significance of "obesity paradox" for CTO interventions.

背景:多项慢性全闭塞(CTO)研究都描述了肥胖悖论对全因死亡率的影响。然而,关于超重和肥胖患者的衰老对CTO再通患者长期心脏事件的影响研究较少:共招募了 458 名接受 CTO 干预治疗的患者(64.4 ± 11.3 岁,403 名男性)。超重/肥胖组包括体重指数(BMI)≧24 kg/m2的311名患者,非肥胖组包括147名患者。在中位随访40.0(17.9-61.4)个月后,对422名成功真腔再通的患者进行了靶病变失败[TLF:心脏死亡、靶血管心肌梗死(TVMI)、靶病变血管再通(TLR)]的进一步评估:随访期间,心源性死亡、TVMI、TLR、TLF 和支架血栓的发生率分别为 1.9%、1.9%、9.2%、10.7% 和 0.5%。超重/肥胖组的无 TVMI 生存率略高于非肥胖组(经对数秩检验,P = 0.067)。结论对于真腔再通的 CTO 患者,成功再通后发生 TVMI 的风险较高,这一点在以下患者中相当明显
{"title":"Impact of aging on long-term cardiac outcomes of true-lumen recanalized chronic total occlusions in patients with overweight/obesity.","authors":"Jen-Fang Cheng, Chien-Lin Lee, Jiunn-Yang Chiang, Shih-Chi Liu, Chi-Hung Huang, Jun-Ting Liou, Chi-Jen Chang, Cheng-Ting Tsai, Chia-Ti Tsai, Yi-Chih Wang, Juey-Jen Hwang","doi":"10.1038/s41366-024-01623-2","DOIUrl":"https://doi.org/10.1038/s41366-024-01623-2","url":null,"abstract":"<p><strong>Background: </strong>Obesity paradox addressing all-cause mortality has been described in several chronic total occlusion (CTO) studies. However, the impact of aging on long-term cardiac events in patients with overweight and obesity with CTO recanalization were less studied.</p><p><strong>Methods: </strong>A total of 458 patients (64.4 ± 11.3 years, 403 male) with CTO interventions were enrolled. The overweight/obesity group included 311 patients with body mass index (BMI) ≧24 kg/m<sup>2</sup> and the non-obesity group included 147. With a median follow-up of 40.0 (17.9-61.4) months, 422 patients with successful true-lumen recanalization were further assessed for target lesion failure [TLF: cardiac death, target vessel myocardial infarction (TVMI), target lesion revascularization (TLR)].</p><p><strong>Results: </strong>At follow-up, the rates of cardiac death, TVMI, TLR, TLF, and stent thrombosis were 1.9%, 1.9%, 9.2%, 10.7%, and 0.5%, respectively. The TVMI-free survival was borderline better (p = 0.067 by log-rank test) in overweight/obesity than non-obesity group. Among patients <65 years of age, the TVMI-free survival was significantly better in the overweight/obesity group (p = 0.013 compared to non-obesity group by log-rank test). In multivariate Cox regression model, the non-obesity patients younger than 65 years were at a higher risk of TVMI, not only among those <65 years of age (hazard ratio = 11.0, 95% CI = 1.1-106.0) but also among the whole patients (hazard ratio=6.9, 95% CI = 1.4-35.1) with successful CTO recanalization.</p><p><strong>Conclusions: </strong>For those with true-lumen recanalized CTO, the higher risk of TVMI after successful recanalization was rather evident in patients <65 years of age and without overweight/obesity, suggesting that aging might attenuate prognostic significance of \"obesity paradox\" for CTO interventions.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132686","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}
引用次数: 0
Metabolic adaptation following gastric bypass surgery: results from a 2-year observational study. 胃旁路手术后的代谢适应:为期两年的观察研究结果。
IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-09-03 DOI: 10.1038/s41366-024-01585-5
Fathimath Naseer, Shu-Dong Zhang, Alexander D Miras, Tamsyn Redpath, Melanie Martin, Adele Boyd, Heather Spence, Dimitri J Pournaras, Zsolt Bodnar, David Kerrigan, Carel W le Roux, M Barbara E Livingstone, Ruth K Price

Background/objectives: Metabolic adaptation is the lowering of basal metabolic rate (BMR) beyond what is predicted from changes in fat mass (FM) and fat-free mass (FFM) and may hamper weight-loss progression. It is unclear whether metabolic adaptation occurs following gastric bypass surgery (GBP) and if it persists. The aim of this study was to evaluate the reduction in BMR that is not explained by changes in body composition in patients following GBP compared to a weight-stable comparator group.

Subjects: Thirty-one patients [77.4% female; mean BMI 45.5(SD 7.0) kg/m2; age 47.4(11.6)y] who underwent GBP, and 32 time-matched comparators [50% female; BMI 27.2(4.6) kg/m2; age 41.8(13.6)y) were evaluated at 1-month pre-surgery, 3-, 12- and 24-months post-surgery.

Methods: BMR was measured under standardised residential conditions using indirect calorimetry and body composition using DXA. Linear regression analyses assessed metabolic adaptation post-surgery.

Results: After surgery, patients lost a quarter of their body weight [-25.6%(1.8%); p < 0.0001] consisting mainly of FM (4:1 FM to FFM loss ratio) at 24-months post-surgery. Absolute BMR (MJ/d) reduced by 25.7% at 24-months post-surgery with values becoming similar to the comparator group from 3-months post-surgery. Positive associations were observed between changes in BMR and changes in FFM and FM (P < 0.03). Metabolic adaptation was present in patients during the 1) rapid weight loss phase (6.9 kg/month at 3-months post-surgery) (p = 0.011), 2) slower weight loss phase (1.6 kg/month from 3 to 12-months post-surgery) (p < 0.0001), and, 3) weight maintenance phase (24-months post-surgery) (p = 0.00073). However, the degree of metabolic adaptation observed in GBP patients was similar to the weight-stable comparator group (no metabolic adaptation) from 12-months post-surgery onwards (3-months; p = 0.01, 12-months; p = 0.26, 24-months post-surgery; p = 0.70).

Conclusion: These results suggest that there is a potential biological mechanism of surgery that attenuates the expected postoperative downregulation in BMR thus helping GBP patients maintain weight loss.

背景/目的:代谢适应是指基础代谢率(BMR)的降低超出了根据脂肪量(FM)和无脂肪量(FFM)的变化所预测的水平,可能会阻碍减肥的进展。目前还不清楚胃旁路手术(GBP)后是否会发生代谢适应,以及这种适应是否会持续。本研究的目的是评估胃旁路手术后患者与体重稳定的参照组相比,身体成分变化无法解释的基础代谢率下降情况:接受 GBP 的 31 名患者[77.4% 为女性;平均 BMI 45.5(标清 7.0)kg/m2;年龄 47.4(11.6)岁]和 32 名时间匹配的对比组患者[50% 为女性;BMI 27.2(4.6)kg/m2;年龄 41.8(13.6)岁]分别在手术前 1 个月、手术后 3 个月、12 个月和 24 个月接受评估:方法: 在标准化居住条件下,使用间接热量计测量血液中的热量,并使用 DXA 测量身体成分。线性回归分析评估了手术后的代谢适应性:结果:手术后,患者体重减轻了四分之一[-25.6%(1.8%); p 结论:这些结果表明,手术后的新陈代谢适应性具有潜在的潜力:这些结果表明,手术存在一种潜在的生物机制,可减轻预期的术后 BMR 下调,从而帮助 GBP 患者保持体重减轻。
{"title":"Metabolic adaptation following gastric bypass surgery: results from a 2-year observational study.","authors":"Fathimath Naseer, Shu-Dong Zhang, Alexander D Miras, Tamsyn Redpath, Melanie Martin, Adele Boyd, Heather Spence, Dimitri J Pournaras, Zsolt Bodnar, David Kerrigan, Carel W le Roux, M Barbara E Livingstone, Ruth K Price","doi":"10.1038/s41366-024-01585-5","DOIUrl":"https://doi.org/10.1038/s41366-024-01585-5","url":null,"abstract":"<p><strong>Background/objectives: </strong>Metabolic adaptation is the lowering of basal metabolic rate (BMR) beyond what is predicted from changes in fat mass (FM) and fat-free mass (FFM) and may hamper weight-loss progression. It is unclear whether metabolic adaptation occurs following gastric bypass surgery (GBP) and if it persists. The aim of this study was to evaluate the reduction in BMR that is not explained by changes in body composition in patients following GBP compared to a weight-stable comparator group.</p><p><strong>Subjects: </strong>Thirty-one patients [77.4% female; mean BMI 45.5(SD 7.0) kg/m<sup>2</sup>; age 47.4(11.6)y] who underwent GBP, and 32 time-matched comparators [50% female; BMI 27.2(4.6) kg/m<sup>2</sup>; age 41.8(13.6)y) were evaluated at 1-month pre-surgery, 3-, 12- and 24-months post-surgery.</p><p><strong>Methods: </strong>BMR was measured under standardised residential conditions using indirect calorimetry and body composition using DXA. Linear regression analyses assessed metabolic adaptation post-surgery.</p><p><strong>Results: </strong>After surgery, patients lost a quarter of their body weight [-25.6%(1.8%); p < 0.0001] consisting mainly of FM (4:1 FM to FFM loss ratio) at 24-months post-surgery. Absolute BMR (MJ/d) reduced by 25.7% at 24-months post-surgery with values becoming similar to the comparator group from 3-months post-surgery. Positive associations were observed between changes in BMR and changes in FFM and FM (P < 0.03). Metabolic adaptation was present in patients during the 1) rapid weight loss phase (6.9 kg/month at 3-months post-surgery) (p = 0.011), 2) slower weight loss phase (1.6 kg/month from 3 to 12-months post-surgery) (p < 0.0001), and, 3) weight maintenance phase (24-months post-surgery) (p = 0.00073). However, the degree of metabolic adaptation observed in GBP patients was similar to the weight-stable comparator group (no metabolic adaptation) from 12-months post-surgery onwards (3-months; p = 0.01, 12-months; p = 0.26, 24-months post-surgery; p = 0.70).</p><p><strong>Conclusion: </strong>These results suggest that there is a potential biological mechanism of surgery that attenuates the expected postoperative downregulation in BMR thus helping GBP patients maintain weight loss.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125686","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}
引用次数: 0
Varying optimal power for height-standardisation of childhood weight, fat mass and fat-free mass across the obesity epidemic. 在肥胖症流行期间,儿童体重、脂肪量和无脂肪量身高标准化的最佳功率各不相同。
IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-09-03 DOI: 10.1038/s41366-024-01619-y
Mohammed T Hudda, Julie Aarestrup, Christopher G Owen, Jennifer L Baker, Peter H Whincup

Introduction: Childhood adiposity markers can be standardised for height in the form of indices (marker/heightp) to make meaningful comparisons of adiposity patterns within and between individuals of differing heights. The optimal value of p has been shown to differ by birth year, sex, age, and ethnicity. We investigated whether height powers for childhood weight and fat mass (FM) differed by birth year, sex, or age over the period before and during the child obesity epidemic in Copenhagen.

Setting/methods: Population-based cross-sectional study of 391,801 schoolchildren aged 7 years, 10 years and 13 years, born between 1930 and 1996, from the Copenhagen School Health Records Register. Sex- and age-specific estimates of the height powers for weight and FM were obtained using log-log regression, stratified by a decade of birth.

Results: For weight, amongst children born 1930-39, optimal height powers at 7 years were 2.20 (95% CI: 2.19-2.22) for boys and 2.28 (95% CI: 2.26-2.30) for girls. These increased with birth year to 2.82 (95% CI: 2.76-2.87) and 2.92 (95% CI: 2.87-2.97) for boys and girls born in 1990-96, respectively. For FM, amongst those born 1930-39, powers at 7 years were 2.46 (95% CI: 2.42-2.51) and 2.58 (95% CI: 2.53-2.63) for boys and girls, respectively, and increased with birth year reaching 3.89 (95% CI: 3.75-4.02) and 3.93 (95% CI: 3.80-4.06) for boys and girls born 1990-96, respectively. Powers within birth cohort groups for weight and FM were higher at 10 years than at 7 years, though similar increases across groups were observed at both ages. At 13 years, height powers for weight and FM initially increased with the birth year before declining from the 1970s/80s.

Conclusion: Due to increases in the standard deviation of weight and FM during the obesity epidemic, optimal height powers needed to standardise childhood weight and FM varied by birth year, sex, and age. Adiposity indices using a uniform height power mean different things for different birth cohort groups, sexes, and ages thus should be interpreted with caution. Alternative methods to account for height in epidemiological analyses are needed.

简介:儿童肥胖标志物可以通过指数(标志物/身高p)的形式对身高进行标准化,从而对不同身高个体内部和之间的肥胖模式进行有意义的比较。p 的最佳值因出生年份、性别、年龄和种族而异。我们研究了在哥本哈根儿童肥胖症流行之前和流行期间,儿童体重和脂肪量(FM)的身高幂是否因出生年份、性别或年龄而异:基于人口的横断面研究,研究对象为哥本哈根学校健康记录登记册中的 391,801 名 7 岁、10 岁和 13 岁学龄儿童,他们分别出生于 1930 年至 1996 年之间。研究采用对数回归法,按出生年代分层,得出了不同性别和年龄的体重和FM的身高权重估计值:在体重方面,1930-39 年出生的儿童 7 岁时的最佳身高幂分别为:男孩 2.20(95% CI:2.19-2.22),女孩 2.28(95% CI:2.26-2.30)。随着出生年份的增加,1990-1996 年出生的男孩和女孩的身高分别为 2.82(95% CI:2.76-2.87)和 2.92(95% CI:2.87-2.97)。就FM而言,在1930-39年出生的人群中,7岁时男孩和女孩的FM值分别为2.46(95% CI:2.42-2.51)和2.58(95% CI:2.53-2.63),并随着出生年份的增加而增加,1990-96年出生的男孩和女孩的FM值分别为3.89(95% CI:3.75-4.02)和3.93(95% CI:3.80-4.06)。出生队列组内的体重和FM指数在10岁时高于7岁时,尽管在这两个年龄段观察到各组间有相似的增长。在 13 岁时,体重和容积的身高力量最初随着出生年份的增加而增加,然后从 20 世纪 70/80 年代开始下降:结论:由于肥胖症流行期间体重和容积标准偏差的增加,标准化儿童体重和容积所需的最佳身高幂因出生年份、性别和年龄而异。使用统一身高幂的肥胖指数对不同出生组群、性别和年龄的人有不同的意义,因此应谨慎解释。在流行病学分析中,需要采用其他方法来计算身高。
{"title":"Varying optimal power for height-standardisation of childhood weight, fat mass and fat-free mass across the obesity epidemic.","authors":"Mohammed T Hudda, Julie Aarestrup, Christopher G Owen, Jennifer L Baker, Peter H Whincup","doi":"10.1038/s41366-024-01619-y","DOIUrl":"https://doi.org/10.1038/s41366-024-01619-y","url":null,"abstract":"<p><strong>Introduction: </strong>Childhood adiposity markers can be standardised for height in the form of indices (marker/height<sup>p</sup>) to make meaningful comparisons of adiposity patterns within and between individuals of differing heights. The optimal value of p has been shown to differ by birth year, sex, age, and ethnicity. We investigated whether height powers for childhood weight and fat mass (FM) differed by birth year, sex, or age over the period before and during the child obesity epidemic in Copenhagen.</p><p><strong>Setting/methods: </strong>Population-based cross-sectional study of 391,801 schoolchildren aged 7 years, 10 years and 13 years, born between 1930 and 1996, from the Copenhagen School Health Records Register. Sex- and age-specific estimates of the height powers for weight and FM were obtained using log-log regression, stratified by a decade of birth.</p><p><strong>Results: </strong>For weight, amongst children born 1930-39, optimal height powers at 7 years were 2.20 (95% CI: 2.19-2.22) for boys and 2.28 (95% CI: 2.26-2.30) for girls. These increased with birth year to 2.82 (95% CI: 2.76-2.87) and 2.92 (95% CI: 2.87-2.97) for boys and girls born in 1990-96, respectively. For FM, amongst those born 1930-39, powers at 7 years were 2.46 (95% CI: 2.42-2.51) and 2.58 (95% CI: 2.53-2.63) for boys and girls, respectively, and increased with birth year reaching 3.89 (95% CI: 3.75-4.02) and 3.93 (95% CI: 3.80-4.06) for boys and girls born 1990-96, respectively. Powers within birth cohort groups for weight and FM were higher at 10 years than at 7 years, though similar increases across groups were observed at both ages. At 13 years, height powers for weight and FM initially increased with the birth year before declining from the 1970s/80s.</p><p><strong>Conclusion: </strong>Due to increases in the standard deviation of weight and FM during the obesity epidemic, optimal height powers needed to standardise childhood weight and FM varied by birth year, sex, and age. Adiposity indices using a uniform height power mean different things for different birth cohort groups, sexes, and ages thus should be interpreted with caution. Alternative methods to account for height in epidemiological analyses are needed.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125687","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}
引用次数: 0
Tirzepatide outcompetes long-acting insulin in managing type 2 diabetes: a meta-analysis of three phase 3 randomized controlled trials. 在控制 2 型糖尿病方面,替扎帕肽优于长效胰岛素:三项第三阶段随机对照试验的荟萃分析。
IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-08-29 DOI: 10.1038/s41366-024-01621-4
Moein Ala, Razieh Mohammad Jafari, Ahmad Reza Dehpour, Mohammad Poursalehian

In this systematic review and meta-analysis, we compared the efficacy and safety of tirzepatide with those of long-acting or ultra-long-acting insulin for type 2 diabetes. PubMed, Web of Science, Scopus, and Google Scholar were searched from the inception to August 20, 2023. All clinical trials or randomized clinical trials comparing the efficacy of tirzepatide with long-acting or ultra-long-acting insulin for treating type 2 diabetes were included. Three randomized clinical trials, namely SURPASS-3, SURPASS-4, and SURPASS-AP-Combo, with 4339 patients were included. Compared with daily insulin glargine and degludec, once-weekly tirzepatide significantly decreased HbA1c (WMD -1.08%, 95% CI (-1.37, -0.78)), 2h-posprandial blood sugar (BS) (WMD -28.19 mg/dL, 95% CI (-44.98, -11.41)), pre-meal BS (WMD -11.86 mg/dL, 95% CI (-22.83, -0.9)), body weight (WMD -10.61 kg, 95% CI (-13.24, -7.97)), systolic blood pressure (WMD -6.47 mmHg, 95% CI (-8.32, -4.61)), diastolic blood pressure (WMD -2.30 mmHg, 95% CI (-3.05, -1.55)), total cholesterol (WMD -4.78%, 95% CI (-7.05, -2.50)), triglyceride (WMD -14.49%, 95% CI (-19.55, -9.43)), LDL cholesterol (WMD -5.98%, 95% CI (-9.83, -2.13)), and VLDL cholesterol (WMD -14.18%, 95% CI (-19.03, -9.33)) and increased HDL cholesterol (WMD 7.13%, 95% CI (-9.83, -2.13)), with a lower risk of hypoglycemia defined as BS ≤ 70 mg/dL (RR 0.46, 95% CI (0.28, 0.75)). All doses of once-weekly tirzepatide (5 mg, 10 mg, and 15 mg) were superior or non-inferior to insulin. Once-weekly tirzepatide can be a substitution for long-acting insulin in type 2 diabetes with a greater efficacy.

在这项系统综述和荟萃分析中,我们比较了替哌肽与长效或超长效胰岛素治疗 2 型糖尿病的疗效和安全性。我们检索了 PubMed、Web of Science、Scopus 和 Google Scholar 从开始到 2023 年 8 月 20 日的所有文献。纳入了所有比较替扎帕肽与长效或超长效胰岛素治疗 2 型糖尿病疗效的临床试验或随机临床试验。其中包括三项随机临床试验,即 SURPASS-3、SURPASS-4 和 SURPASS-AP-Combo,共有 4339 名患者参加。与每日使用格列奈胰岛素和德格列奈胰岛素相比,每周一次使用替扎帕肽可显著降低 HbA1c(WMD -1.08%,95% CI (-1.37, -0.78))、餐前 2 小时血糖(BS)(WMD -28.19 mg/dL,95% CI (-44.98, -11.41)、餐前 BS(WMD -11.86 mg/dL,95% CI(-22.83,-0.9))、体重(WMD -10.61 kg,95% CI(-13.24,-7.97))、收缩压(WMD -6.47 mmHg,95% CI(-8.32,-4.61))、舒张压(WMD -2.30毫米汞柱,95% CI(-3.05,-1.55))、总胆固醇(WMD -4.78%,95% CI(-7.05,-2.50))、甘油三酯(WMD -14.49%,95% CI(-19.55,-9.43))、低密度脂蛋白胆固醇(WMD -5.98%,95% CI(-9.83,-2.13))和超低密度脂蛋白胆固醇(WMD -14.18%,95% CI (-19.03,-9.33))和高密度脂蛋白胆固醇增加(WMD 7.13%,95% CI (-9.83,-2.13)),而 BS ≤ 70 mg/dL 的低血糖风险较低(RR 0.46,95% CI (0.28,0.75))。所有剂量的每周一次替扎帕肽(5 毫克、10 毫克和 15 毫克)均优于或不劣于胰岛素。在2型糖尿病患者中,一周一次的替扎帕肽可替代长效胰岛素,且疗效更好。
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引用次数: 0
Exposure to gestational diabetes mellitus in utero impacts hippocampal functional connectivity in response to food cues in children. 宫内妊娠糖尿病会影响儿童海马对食物线索的功能连接。
IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-08-28 DOI: 10.1038/s41366-024-01608-1
Sixiu Zhao, Lorenzo Semeia, Ralf Veit, Shan Luo, Brendan C Angelo, Ting Chow, Andreas L Birkenfeld, Hubert Preissl, Anny H Xiang, Kathleen A Page, Stephanie Kullmann

Objectives: Intrauterine exposure to gestational diabetes mellitus (GDM) increases the risk of obesity in the offspring, but little is known about the underlying neural mechanisms. The hippocampus is crucial for food intake regulation and is vulnerable to the effects of obesity. The purpose of the study was to investigate whether GDM exposure affects hippocampal functional connectivity during exposure to food cues using functional magnetic resonance imaging (fMRI).

Methods: Participants were 90 children age 7-11 years (53 females) who underwent an fMRI-based visual food cue task in the fasted state. Hippocampal functional connectivity (FC) was examined using generalized psychophysiological interaction in response to food versus non-food cues. Hippocampal FC was compared between children with and without GDM exposure, while controlling for possible confounding effects of age, sex and waist-to-hip ratio. In addition, the influence of childhood and maternal obesity were investigated using multiple regression models.

Results: While viewing high caloric food cues compared to non-food cure, children with GDM exposure exhibited higher hippocampal FC to the insula and striatum (i.e., putamen, pallidum and nucleus accumbens) compared to unexposed children. With increasing BMI, children with GDM exposure had lower hippocampal FC to the somatosensory cortex (i.e., postcentral gyrus).

Conclusions: Intrauterine exposure to GDM was associated with higher food-cue induced hippocampal FC especially to reward processing regions. Future studies with longitudinal measurements are needed to clarify whether altered hippocampal FC may raise the risk of the development of metabolic diseases later in life.

目的:宫内妊娠糖尿病(GDM)会增加后代肥胖的风险,但人们对其潜在的神经机制知之甚少。海马区对食物摄入调节至关重要,易受肥胖的影响。本研究的目的是利用功能性磁共振成像(fMRI)技术,研究暴露于GDM是否会影响暴露于食物线索时的海马功能连接:方法:90名7-11岁的儿童(53名女性)在空腹状态下接受了基于fMRI的视觉食物线索任务。利用泛化心理生理交互作用对食物与非食物线索的海马功能连接(FC)进行了检测。在控制年龄、性别和腰臀比等可能的混杂影响的同时,还比较了有无GDM暴露的儿童的海马功能连通性。此外,还使用多元回归模型研究了儿童肥胖和母亲肥胖的影响:结果:与非食物疗法相比,在观看高热量食物线索时,与未暴露的儿童相比,暴露于 GDM 的儿童表现出更高的海马 FC 至岛叶和纹状体(即普鲁士门、苍白球和凹凸核)。随着体重指数(BMI)的增加,暴露于GDM的儿童海马体至躯体感觉皮层(即中央后回)的FC较低:结论:宫内暴露于 GDM 与食物线索诱发的海马 FC(尤其是奖赏加工区域)较高有关。未来的研究需要进行纵向测量,以明确海马FC的改变是否会增加日后患代谢性疾病的风险。
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引用次数: 0
Does menu calorie labelling cause or exacerbate eating disorders? 菜单卡路里标签会导致或加剧饮食失调吗?
IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-08-28 DOI: 10.1038/s41366-024-01622-3
Jane Brealey, Rebecca Evans, Amy Finlay, Thomas Gough, Megan Polden, I Gusti Ngurah Edi Putra, Loukia Tzavella, Rozemarijn Witkam, Eric Robinson

ER and JB were responsible for conceptualisation and study design. JB screened prospective eligible studies, conducted the literature review and wrote the first draft of the manuscript. RE, AF, TG, MP, IP, LT and RW reviewed the literature and contributed to writing. All authors contributed to the manuscript writing, revision, editing, and approved the submitted version.

ER 和 JB 负责构思和研究设计。JB 筛选了符合条件的前瞻性研究,进行了文献综述,并撰写了手稿初稿。RE、AF、TG、MP、IP、LT 和 RW 对文献进行了审阅并参与了撰写。所有作者都参与了手稿的撰写、修改和编辑,并批准了提交的版本。
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引用次数: 0
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International Journal of Obesity
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