Oliveira Ferreira Clílton Kraüss de, Campolim Clara Machado, Zordão Olívia Pizetta, Simabuco Fernando Moreira, Anaruma Chadi Pellegrini, Pereira Rodrigo Martins, Boico Vitor Ferreira, Salvino Luiz Guilherme, Costa Maíra Maftoum, Ruiz Nathalia Quintero, de Moura Leandro Pereira, Saad Mario Jose Abdalla, Costa Soraia Katia Pereira, Kim Young-Bum, Prada Patricia Oliveira
Faculty of Applied Sciences, State University of Campinas, Limeira, SP, Brazil.
Department of Internal Medicine, Faculty of Medical Science, State University of Campinas, Campinas, SP, Brazil.
Toxicol Rep. 2023 Jun 15;11:10-22. doi: 10.1016/j.toxrep.2023.06.002. eCollection 2023 Dec.
Air pollution affects energy homeostasis detrimentally. Yet, knowledge of how each isolated pollutant can impact energy metabolism remains incomplete. The present study was designed to investigate the distinct effects of 1,2-naphthoquinone (1,2-NQ) on energy metabolism since this pollutant increases at the same rate as diesel combustion. In particular, we aimed to determine in vivo effects of subchronic exposure to 1,2-NQ on metabolic and inflammatory parameters of wild-type mice (WT) and to explore the involvement of tumor necrosis factor receptor 1 (TNFR1) and toll-like receptor 4 (TLR4) in this process. Males WT, TNFR1KO, and TLR4KO mice at eight weeks of age received 1,2-NQ or vehicle via nebulization five days a week for 17 weeks. In WT mice, 1,2-NQ slightly decreased the body mass compared to vehicle-WT. This effect was likely due to a mild food intake reduction and increased energy expenditure (EE) observed after six weeks of exposure. After nine weeks of exposure, we observed higher fasting blood glucose and impaired glucose tolerance, whereas insulin sensitivity was slightly improved compared to vehicle-WT. After 17 weeks of 1,2-NQ exposure, WT mice displayed an increased percentage of M1 and a decreased (p = 0.057) percentage of M2 macrophages in adipose tissue. The deletion of TNFR1 and TLR4 abolished most of the metabolic impacts caused by 1,2-NQ exposure, except for the EE and insulin sensitivity, which remained high in these mice under 1,2-NQ exposure. Our study demonstrates for the first time that subchronic exposure to 1,2-NQ affects energy metabolism in vivo. Although 1,2-NQ increased EE and slightly reduced feeding and body mass, the WT mice displayed higher inflammation in adipose tissue and impaired fasting blood glucose and glucose tolerance. Thus, in vivo subchronic exposure to 1,2-NQ is harmful, and TNFR1 and TLR4 are partially involved in these outcomes.
空气污染对能量平衡有不利影响。然而，关于每种单一污染物如何影响能量代谢的知识仍不完整。本研究旨在调查1,2-萘醌（1,2-NQ）对能量代谢的独特影响，因为这种污染物的增加速率与柴油燃烧相同。具体而言，我们旨在确定亚慢性暴露于1,2-NQ对野生型小鼠（WT）代谢和炎症参数的体内影响，并探讨肿瘤坏死因子受体1（TNFR1）和Toll样受体4（TLR4）在此过程中的作用。8周龄的雄性WT、TNFR1基因敲除（TNFR1KO）和TLR4基因敲除（TLR4KO）小鼠每周5天通过雾化接受1,2-NQ或赋形剂，持续17周。在WT小鼠中，与接受赋形剂的WT小鼠相比，1,2-NQ使体重略有下降。这种影响可能是由于暴露6周后观察到食物摄入量略有减少和能量消耗（EE）增加。暴露9周后，我们观察到空腹血糖升高和葡萄糖耐量受损，而与接受赋形剂的WT小鼠相比，胰岛素敏感性略有改善。1,2-NQ暴露17周后，WT小鼠脂肪组织中M1巨噬细胞百分比增加，M2巨噬细胞百分比降低（p = 0.057）。TNFR1和TLR4的缺失消除了1,2-NQ暴露引起的大部分代谢影响，但EE和胰岛素敏感性除外，在1,2-NQ暴露下这些小鼠的EE和胰岛素敏感性仍然很高。我们的研究首次证明，亚慢性暴露于1,2-NQ会在体内影响能量代谢。虽然1,2-NQ增加了EE并略微降低了进食量和体重，但WT小鼠脂肪组织中的炎症更高，空腹血糖和葡萄糖耐量受损。因此，体内亚慢性暴露于1,2-NQ是有害的，TNFR1和TLR4部分参与了这些结果。
