Howell George E, Young Darian
Mississippi State University College of Veterinary Medicine, Center for Environmental Health Sciences, Department of Comparative Biomedical Sciences, Mississippi State University, MS, USA.
Mississippi State University College of Veterinary Medicine, Center for Environmental Health Sciences, Department of Comparative Biomedical Sciences, Mississippi State University, MS, USA.
Toxicol In Vitro. 2024 Jun;98:105831. doi: 10.1016/j.tiv.2024.105831. Epub 2024 Apr 20.
Exposure to persistent organic pollutants (POPs), including organochlorine (OC) pesticide POPs, has been associated with the increased prevalence of obesity and type 2 diabetes. However, the underlying mechanisms through which exposure to these compounds may promote obesity and metabolic dysfunction remain an area of active investigation. To this end, the concentration dependent effects of an environmentally relevant mixture of OC pesticide POPs on adipocyte function was explored utilizing a translationally relevant immortalized human subcutaneous preadipocyte/adipocyte model. Briefly, immortalized human preadipocytes/adipocytes were exposed to a mixture of dichlorodiphenyldichloroethylene (DDE), trans-nonachlor, and oxychlordane (DTO) then key indices of preadipocyte/adipocyte function were assessed. Exposure to DTO did not alter adipogenesis. However, in mature adipocytes, exposure to DTO slightly increased fatty acid uptake whereas isoproterenol stimulated lipolysis, basal and insulin stimulated glucose uptake, mitochondrial membrane potential, and cellular ATP levels were all significantly decreased. DTO significantly increased Staphylococcus aureus infection induced increases in expression of pro-inflammatory cytokines IL-6, IL-1β, and Mcp-1 as well as the adipokine resistin. Taken together, the present data demonstrated exposure to an environmentally relevant mixture of OC pesticide compounds can alter mature adipocyte function in a translationally relevant human adipocyte model which further supports the adipose tissue as an effector site of OC pesticide POPs action.
接触持久性有机污染物（POPs），包括有机氯（OC）农药类POPs，与肥胖症和2型糖尿病患病率的增加有关。然而，接触这些化合物可能促进肥胖和代谢功能障碍的潜在机制仍是一个积极研究的领域。为此，利用一个具有转化相关性的永生化人类皮下前脂肪细胞/脂肪细胞模型，探讨了与环境相关的OC农药类POPs混合物对脂肪细胞功能的浓度依赖性影响。简而言之，将永生化人类前脂肪细胞/脂肪细胞暴露于二氯二苯二氯乙烯（DDE）、反式九氯和顺式氯丹（DTO）的混合物中，然后评估前脂肪细胞/脂肪细胞功能的关键指标。接触DTO并没有改变脂肪生成。然而，在成熟脂肪细胞中，接触DTO会轻微增加脂肪酸摄取，而异丙肾上腺素刺激的脂解、基础和胰岛素刺激的葡萄糖摄取、线粒体膜电位以及细胞ATP水平均显著降低。DTO显著增加了金黄色葡萄球菌感染诱导的促炎细胞因子IL-6、IL-1β和Mcp-1以及脂肪因子抵抗素表达的增加。综上所述，目前的数据表明，在一个具有转化相关性的人类脂肪细胞模型中，接触与环境相关的OC农药化合物混合物可改变成熟脂肪细胞功能，这进一步支持了脂肪组织作为OC农药类POPs作用的效应位点。
