肥胖原三丁基廷对小鼠代谢健康的跨代影响:与西方饮食的相互作用。

IF 3.8 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM
Richard C Chang, Yikai Huang, Kaitlin To, Ryan Scott Whitlock, Katelyn Uyen Nguyen, Michelle Clara Joemon, Miranda Lopez, Kritin Guy Deeprompt, Toshi Shioda, Bruce Blumberg
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引用次数: 0

摘要

肥胖是一个全球性的健康危机,越来越多的证据表明,环境因素,如暴露于内分泌干扰化学物质(EDCs)与肥胖的发展有关。本研究考察了暴露于模型肥胖原三丁基锡(TBT)对肥胖和代谢健康的跨代影响,特别关注这些影响如何与美国饮食消费的第50百分位模型饮食(总西方饮食,TWD)相互作用。怀孕的F0坝暴露于TBT,它们的后代在成年后接受不同的饮食,包括高脂肪饮食和TWD,跨越多个后代(F1-F3)。我们发现,TBT暴露使雄性后代容易增加脂肪积累,胰岛素抵抗和代谢功能障碍,这些影响被TWD加剧。值得注意的是,在TWD暴露下,雄性后代表现出瘦素水平升高、肝纤维化和炎症反应,这表明肥胖原暴露与饮食脂肪摄入之间存在附加或协同关系。这些跨代效应在女性后代中基本不存在,这强调了性别对环境和饮食因素的脆弱性。我们的研究结果表明,产前TBT暴露和TWD的结合放大了代际代谢紊乱,强调了在解决肥胖流行问题时需要考虑环境化学物质和饮食模式。这项研究强调了早期EDC暴露和饮食因素在塑造长期代谢健康中的关键作用,以及肥胖症和代谢紊乱易感性的跨代编程的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Transgenerational Effects of the Obesogen Tributyltin on Metabolic Health in Mice: Interactions with a Western Diet.

Obesity is a global health crisis, with increasing evidence linking environmental factors such as exposure to endocrine-disrupting chemicals (EDCs) to its development. This study examines the transgenerational effects of exposure to the model obesogen, tributyltin (TBT), on obesity and metabolic health, specifically focusing on how these effects interact with a diet modeling the 50th percentile of US dietary consumption (the Total Western Diet, TWD). Pregnant F0 dams were exposed to TBT, and their offspring were subjected at adulthood to different diets, including a high-fat diet and TWD, across multiple subsequent generations (F1-F3). We found that TBT exposure predisposed male offspring to increased fat accumulation, insulin resistance, and metabolic dysfunction, effects that were exacerbated by the TWD. Notably, male offspring displayed elevated leptin levels, hepatic fibrosis, and inflammatory responses under TWD exposure, suggesting an additive or synergistic relationship between obesogen exposure and dietary fat intake. These transgenerational effects were largely absent in female offspring, underscoring sex-specific vulnerabilities to environmental and dietary factors. Our results demonstrated that the combination of prenatal TBT exposure and TWD amplifies metabolic disturbances across generations, highlighting the need to consider both environmental chemicals and dietary patterns in addressing the obesity pandemic. This study underscores the critical role of early-life EDC exposures and dietary factors in shaping long-term metabolic health and the potential for transgenerational programming of susceptibility to obesity and metabolic disorders.

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来源期刊
Endocrinology
Endocrinology 医学-内分泌学与代谢
CiteScore
8.10
自引率
4.20%
发文量
195
审稿时长
2-3 weeks
期刊介绍: The mission of Endocrinology is to be the authoritative source of emerging hormone science and to disseminate that new knowledge to scientists, clinicians, and the public in a way that will enable "hormone science to health." Endocrinology welcomes the submission of original research investigating endocrine systems and diseases at all levels of biological organization, incorporating molecular mechanistic studies, such as hormone-receptor interactions, in all areas of endocrinology, as well as cross-disciplinary and integrative studies. The editors of Endocrinology encourage the submission of research in emerging areas not traditionally recognized as endocrinology or metabolism in addition to the following traditionally recognized fields: Adrenal; Bone Health and Osteoporosis; Cardiovascular Endocrinology; Diabetes; Endocrine-Disrupting Chemicals; Endocrine Neoplasia and Cancer; Growth; Neuroendocrinology; Nuclear Receptors and Their Ligands; Obesity; Reproductive Endocrinology; Signaling Pathways; and Thyroid.
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