School of Biodiversity One Health and Veterinary Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
University of Nottingham, Sutton Bonington Campus, Loughborough, UK.
J Neuroendocrinol. 2024 Jan;36(1):e13358. doi: 10.1111/jne.13358. Epub 2023 Dec 12.
Over recent decades, an extensive array of anthropogenic chemicals have entered the environment and have been implicated in the increased incidence of an array of diseases, including metabolic syndrome. The ubiquitous presence of these environmental chemicals (ECs) necessitates the use of real-life exposure models to the assess cumulative risk burden to metabolic health. Sheep that graze on biosolids-treated pastures are exposed to a real-life mixture of ECs such as phthalates, per- and polyfluoroalkyl substances, heavy metals, pharmaceuticals, pesticides, and metabolites thereof, and this EC exposure can result in metabolic disorders in their offspring. Using this model, we evaluated the effects of gestational exposure to a complex EC mixture on plasma triglyceride (TG) concentrations and metabolic and epigenetic regulatory genes in tissues key to energy regulation and storage, including the hypothalamus, liver, and adipose depots of 11-month-old male offspring. Our results demonstrated a binary effect of EC exposure on gene expression particularly in the hypothalamus. Principal component analysis revealed two subsets (B-S1 [n = 6] and B-S2 [n = 4]) within the biosolids group (B, n = 10), relative to the controls (C, n = 11). Changes in body weight, TG levels, and in gene expression in the hypothalamus, and visceral and subcutaneous fat were apparent between biosolid and control and the two subgroups of biosolids animals. These findings demonstrate that gestational exposure to an EC mixture results in differential regulation of metabolic processes in adult male offspring. Binary effects on hypothalamic gene expression and altered expression of lipid metabolism genes in visceral and subcutaneous fat, coupled with phenotypic outcomes, point to differences in individual susceptibility to EC exposure that could predispose vulnerable individuals to later metabolic dysfunction.
在过去几十年中，大量人为化学物质进入环境，并与一系列疾病（包括代谢综合征）的发病率增加有关。这些环境化学物质（ECs）无处不在，因此需要使用现实生活中的暴露模型来评估对代谢健康的累积风险负担。在生物固体处理过的牧场上放牧的绵羊会接触到各种 ECs，如邻苯二甲酸酯、全氟和多氟烷基物质、重金属、药物、农药及其代谢物，这种 EC 暴露会导致其后代出现代谢紊乱。使用这种模型，我们评估了妊娠期暴露于复杂 EC 混合物对血浆甘油三酯 (TG) 浓度以及组织中代谢和表观遗传调节基因的影响，这些组织对能量调节和储存至关重要，包括下丘脑、肝脏和脂肪组织。我们的研究结果表明，EC 暴露对基因表达具有二元效应，特别是在下丘脑中。主成分分析显示，与对照组 (C, n = 11) 相比，生物固体组 (B, n = 10) 中有两个子集 (B-S1 [n = 6] 和 B-S2 [n = 4])。生物固体和对照组以及两组生物固体动物之间的体重、TG 水平以及下丘脑、内脏和皮下脂肪的基因表达变化明显。这些发现表明，妊娠期暴露于 EC 混合物会导致雄性成年后代代谢过程的差异调节。下丘脑基因表达的二元效应以及内脏和皮下脂肪中脂质代谢基因的表达改变，加上表型结果，表明个体对 EC 暴露的敏感性存在差异，这可能使易受影响的个体更容易出现代谢功能障碍。
