Beyond the Surface: Mapping DDE's Metabolic Footprint on Adolescent Obesity.

IF 10.1 1区 环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES
Zhenjiang Li, Shudi Pan, Brittney O Baumert, Jiawen Carmen Chen, Jesse A Goodrich, Hongxu Wang, Sarah Rock, Justin Ryder, Damaskini Valvi, Todd Jenkins, Stephanie Sisley, Xiangping Lin, Scott M Bartell, Thomas H Inge, Stavra Xanthakos, Brooklynn McNeil, Anna R Robuck, Catherine E Mullins, Sandrah P Eckel, Rob S McConnell, Michele A La Merrill, Douglas I Walker, David V Conti, Lida Chatzi
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引用次数: 0

Abstract

Background: Bariatric surgery is an intervention for severe obesity, leading to significant weight loss and metabolic improvements. However, the release of lipophilic chemicals accumulated in adipose tissue during weight loss presents a unique clinical challenge and research opportunity. Dichlorodiphenyldichloroethylene (DDE) is a persistent organic pollutant increasingly recognized as obesogen, while the biological mechanisms through which DDE influences body mass index (BMI) and waist circumference remain underexplored.

Objectives: We aimed to identify metabolic signatures mediating the association between DDE exposure and weight loss by plasma and adipose tissue metabolomics.

Methods: We conducted a longitudinal study involving 60 adolescents with severe obesity undergoing bariatric surgery. We quantified p,p'-DDE concentrations in visceral adipose tissue collected during surgery and analyzed metabolic profiles from both adipose tissues collected at surgery and plasma samples collected at surgery, 6 months, 1 year, and 3 years postoperatively, using gas/liquid chromatography and high-resolution mass spectrometry. We used meet-in-the-middle approach coupled with a series of metabolome-wide association analyses to identify overlapping metabolite associated with both DDE exposure and weight loss outcomes.

Results: Our findings revealed that DDE concentrations in visceral adipose tissue are associated with significant alterations in metabolites locally in adipose tissue pre-surgery and systemically in plasma post-surgery. Eight plasma metabolites were significantly associated with DDE exposure over time, while 27 were associated with BMI. Notably, methylbutyroylcarnitine was identified as a potential mediator, showing a positive association with both exposure and outcome. Eight adipose tissue metabolites were associated with both DDE and longitudinal changes in plasma metabolites, suggesting an indirect pathway linking DDE and weight changes.

Discussion: These findings enhance our understanding of DDE's obesogenic effect. The involved metabolic changes could attenuate the efficacy of bariatric surgery in achieving sustained weight loss, underscoring the importance of integrating environmental health considerations into clinical practice. https://doi.org/10.1289/EHP16341.

表面之外:绘制DDE在青少年肥胖中的代谢足迹。
背景:减肥手术是治疗严重肥胖的一种干预手段,可导致显著的体重减轻和代谢改善。然而,在减肥过程中积累在脂肪组织中的亲脂性化学物质的释放提出了一个独特的临床挑战和研究机会。二氯二苯二氯乙烯(DDE)是一种持久性有机污染物,被越来越多地认为是致肥源,但DDE影响体重指数(BMI)和腰围的生物学机制尚不清楚。目的:我们的目的是通过血浆和脂肪组织代谢组学来确定DDE暴露与体重减轻之间的代谢特征。方法:我们进行了一项涉及60名接受减肥手术的严重肥胖青少年的纵向研究。我们量化了手术中收集的内脏脂肪组织中的p,p'-DDE浓度,并使用气相/液相色谱法和高分辨率质谱法分析了手术中收集的脂肪组织和手术后6个月,1年和3年收集的血浆样本的代谢谱。我们使用中间相遇方法结合一系列代谢组关联分析来确定与DDE暴露和体重减轻结果相关的重叠代谢物。结果:我们的研究结果显示,内脏脂肪组织中的DDE浓度与手术前脂肪组织局部代谢物和手术后全身血浆代谢物的显著改变有关。随着时间的推移,8种血浆代谢物与DDE暴露显著相关,27种与BMI相关。值得注意的是,甲基丁基左旋肉碱被确定为一种潜在的介质,显示出与暴露和结果呈正相关。8种脂肪组织代谢物与DDE和血浆代谢物的纵向变化相关,表明DDE与体重变化之间存在间接联系。讨论:这些发现增强了我们对DDE致肥作用的理解。所涉及的代谢变化可能会减弱减肥手术在实现持续减肥方面的效果,这强调了将环境健康考虑纳入临床实践的重要性。https://doi.org/10.1289/EHP16341。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Environmental Health Perspectives
Environmental Health Perspectives 环境科学-公共卫生、环境卫生与职业卫生
CiteScore
14.40
自引率
2.90%
发文量
388
审稿时长
6 months
期刊介绍: Environmental Health Perspectives (EHP) is a monthly peer-reviewed journal supported by the National Institute of Environmental Health Sciences, part of the National Institutes of Health under the U.S. Department of Health and Human Services. Its mission is to facilitate discussions on the connections between the environment and human health by publishing top-notch research and news. EHP ranks third in Public, Environmental, and Occupational Health, fourth in Toxicology, and fifth in Environmental Sciences.
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