Perinatal High-Fat Diet Influences Ozone-Induced Responses on Pulmonary Oxidant Status and the Molecular Control of Mitophagy in Female Rat Offspring

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.

Keywords: high-fat diet; mitochondria; obesity; oxidative stress; ozone; perinatal; pulmonary toxicity.

MeSH terms

  • Animals
  • Animals, Newborn
  • Diet, High-Fat / adverse effects*
  • Female
  • Gene Expression Profiling
  • Lung / metabolism
  • Lung / pathology*
  • Male
  • Maternal Nutritional Physiological Phenomena
  • Mitochondria / metabolism
  • Mitochondria / pathology*
  • Mitophagy*
  • Oxidants / metabolism*
  • Oxidative Phosphorylation
  • Oxidative Stress
  • Ozone / adverse effects*
  • Pregnancy
  • Prenatal Exposure Delayed Effects / etiology
  • Prenatal Exposure Delayed Effects / pathology*
  • Rats
  • Rats, Long-Evans


  • Oxidants
  • Ozone