Exposure to PCB52 (2,2′,5,5′-tetrachlorobiphenyl) blunts induction of the gene for uncoupling protein 1 (UCP1) in white adipose

IF 4.2 3区 环境科学与生态学 Q2 ENVIRONMENTAL SCIENCES Environmental toxicology and pharmacology Pub Date : 2024-12-13 DOI:10.1016/j.etap.2024.104612
Francoise A. Gourronc, Amanda J. Bullert, Brynn Kyleakin Helm-Kwasny, Andrea Adamcakova-Dodd, Hui Wang, Xuefang Jing, Xueshu Li, Peter S. Thorne, Hans-Joachim Lehmler, James A. Ankrum, Aloysius J. Klingelhutz
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Abstract

Polychlorinated biphenyls (PCBs) are linked to cancer, learning disabilities, liver and cardiovascular disease, and diabetes. Older schools often contain high levels of PCBs, and inhalation is a major source of exposure. Technical PCB mixtures, called Aroclors, and individual dioxin-like PCBs impair adipocyte function, which can lead to type II diabetes. To determine how PCB52, a non-dioxin like PCB congener found in school air, affects adipose, adolescent male and female rats were exposed to PCB52 by nose-only inhibition for 4 h per day for 28 consecutive days. Transcriptomic analysis of white adipose revealed sex-specific differences in gene expression between PCB52- and sham-exposed males and females. Exposed females showed mitochondrial gene changes, including downregulation of the thermogenic uncoupling gene, Ucp1. Human preadipocytes/adipocytes exposed to PCB52 or its main metabolite, 4-OH-PCB52, also showed reduced norepinephrine-induced UCP1 expression. These findings suggest that PCB52 inhalation disrupts thermogenesis in adipose tissue, potentially contributing to metabolic syndrome.
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接触 PCB52(2,2′,5,5′-四氯联苯)会减弱白色脂肪中解偶联蛋白 1(UCP1)基因的诱导作用
多氯联苯(PCBs)与癌症、学习障碍、肝脏和心血管疾病以及糖尿病有关。较老的学校往往含有高浓度的多氯联苯,而吸入是主要的接触来源。技术上的多氯联苯混合物(称为Aroclors)和个别类二恶英多氯联苯会损害脂肪细胞功能,从而导致II型糖尿病。为了确定PCB52(一种在学校空气中发现的与二恶英不同的多氯联苯同系物)对脂肪的影响,研究人员连续28天每天仅通过鼻腔抑制4 h的方式暴露在青春期雄性和雌性大鼠的PCB52中。白色脂肪的转录组学分析揭示了PCB52暴露和假暴露的男性和女性之间基因表达的性别特异性差异。暴露的雌性出现线粒体基因变化,包括产热解偶联基因Ucp1下调。暴露于PCB52或其主要代谢物4-OH-PCB52的人前脂肪细胞/脂肪细胞也显示出去甲肾上腺素诱导的UCP1表达降低。这些发现表明,吸入PCB52会破坏脂肪组织的产热作用,可能导致代谢综合征。
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来源期刊
CiteScore
7.00
自引率
4.70%
发文量
185
审稿时长
34 days
期刊介绍: Environmental Toxicology and Pharmacology publishes the results of studies concerning toxic and pharmacological effects of (human and veterinary) drugs and of environmental contaminants in animals and man. Areas of special interest are: molecular mechanisms of toxicity, biotransformation and toxicokinetics (including toxicokinetic modelling), molecular, biochemical and physiological mechanisms explaining differences in sensitivity between species and individuals, the characterisation of pathophysiological models and mechanisms involved in the development of effects and the identification of biological markers that can be used to study exposure and effects in man and animals. In addition to full length papers, short communications, full-length reviews and mini-reviews, Environmental Toxicology and Pharmacology will publish in depth assessments of special problem areas. The latter publications may exceed the length of a full length paper three to fourfold. A basic requirement is that the assessments are made under the auspices of international groups of leading experts in the fields concerned. The information examined may either consist of data that were already published, or of new data that were obtained within the framework of collaborative research programmes. Provision is also made for the acceptance of minireviews on (classes of) compounds, toxicities or mechanisms, debating recent advances in rapidly developing fields that fall within the scope of the journal.
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