Gourronc Francoise A, Bullert Amanda J, Helm-Kwasny Brynn Kyleakin, Adamcakova-Dodd Andrea, Wang Hui, Jing Xuefang, Li Xueshu, Thorne Peter S, Lehmler Hans-Joachim, Ankrum James A, Klingelhutz Aloysius J
Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, IA, United States.
Interdisciplinary Graduate Program in Neuroscience, University of Iowa, Iowa City, IA, United States.
Environ Toxicol Pharmacol. 2025 Jan;113:104612. doi: 10.1016/j.etap.2024.104612. Epub 2024 Dec 13.
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.
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。老旧学校通常含有高浓度的多氯联苯,吸入是主要的接触源。名为氯丹的工业多氯联苯混合物以及个别类二噁英多氯联苯会损害脂肪细胞功能,进而可能导致II型糖尿病。为了确定学校空气中发现的一种非类二噁英多氯联苯同系物PCB52如何影响脂肪组织,对青春期雄性和雌性大鼠进行了仅通过鼻腔吸入的方式连续28天每天接触4小时PCB52的实验。对白色脂肪组织的转录组分析揭示了PCB52暴露组与假暴露组的雄性和雌性大鼠在基因表达上存在性别特异性差异。暴露的雌性大鼠表现出线粒体基因变化,包括产热解偶联基因Ucp1的下调。暴露于PCB52或其主要代谢产物4-OH-PCB52的人类前脂肪细胞/脂肪细胞也表现出去甲肾上腺素诱导的UCP1表达降低。这些发现表明,吸入PCB52会破坏脂肪组织中的产热过程,可能导致代谢综合征。