Rouschop Sven H, Snow Samantha J, Kodavanti Urmila P, Drittij Marie-José, Maas Lou M, Opperhuizen Antoon, van Schooten Frederik J, Remels Alexander H, Godschalk Roger W
Department of Pharmacology and Toxicology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, 6200 Maastricht, The Netherlands.
Public Health and Integrated Toxicology Division, Center for Public Health and Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Durham, NC 27711, USA.
Int J Mol Sci. 2021 Jul 14;22(14):7551. doi: 10.3390/ijms22147551.
Previous research has shown that a perinatal obesogenic, high-fat diet (HFD) is able to exacerbate ozone-induced adverse effects on lung function, injury, and inflammation in offspring, and it has been suggested that mitochondrial dysfunction is implicated herein. The aim of this study was to investigate whether a perinatal obesogenic HFD affects ozone-induced changes in offspring pulmonary oxidant status and the molecular control of mitochondrial function. For this purpose, female Long-Evans rats were fed a control diet or HFD before and during gestation, and during lactation, after which the offspring were acutely exposed to filtered air or ozone at a young-adult age (forty days). Directly following this exposure, the offspring lungs were examined for markers related to oxidative stress; oxidative phosphorylation; and mitochondrial fusion, fission, biogenesis, and mitophagy. Acute ozone exposure significantly increased pulmonary oxidant status and upregulated the molecular machinery that controls receptor-mediated mitophagy. In female offspring, a perinatal HFD exacerbated these responses, whereas in male offspring, responses were similar for both diet groups. The expression of the genes and proteins involved in oxidative phosphorylation and mitochondrial biogenesis, fusion, and fission was not affected by ozone exposure or perinatal HFD. These findings suggest that a perinatal HFD influences ozone-induced responses on pulmonary oxidant status and the molecular control of mitophagy in female rat offspring.
先前的研究表明，围产期致肥胖的高脂饮食（HFD）能够加剧臭氧对后代肺功能、损伤和炎症的不良影响，并且有人提出线粒体功能障碍与此有关。本研究的目的是调查围产期致肥胖的高脂饮食是否会影响臭氧诱导的后代肺氧化状态变化以及线粒体功能的分子调控。为此，在妊娠前、妊娠期间和哺乳期，给雌性Long-Evans大鼠喂食对照饮食或高脂饮食，之后在成年早期（40天）将后代急性暴露于过滤空气或臭氧中。暴露后，立即检查后代肺中与氧化应激、氧化磷酸化以及线粒体融合、裂变、生物发生和线粒体自噬相关的标志物。急性臭氧暴露显著增加了肺氧化状态，并上调了控制受体介导的线粒体自噬的分子机制。在雌性后代中，围产期高脂饮食加剧了这些反应，而在雄性后代中，两个饮食组的反应相似。参与氧化磷酸化以及线粒体生物发生、融合和裂变的基因和蛋白质的表达不受臭氧暴露或围产期高脂饮食的影响。这些发现表明，围产期高脂饮食会影响臭氧诱导的雌性大鼠后代肺氧化状态反应以及线粒体自噬的分子调控。
