Exposure to air pollution, the fourth leading risk factor for global attributable deaths, has been linked to the development of several noncommunicable diseases. The incidence of thyroid diseases in the United States continues to increase yearly, estimating that over 12% of Americans will develop it during their lifetime. While thyroid disorders are not yet recognized as a noncommunicable disease, they promote the onset of other chronic diseases. Diesel exhaust (DE), an important source of particulate matter and other toxic compounds within traffic-related air pollution, generates reactive oxygen species (ROS) which can lead to oxidative stress in the body. Oxidative stress is the imbalance of ROS and antioxidants in the body and is associated with numerous diseases. The purpose of this study is to assess the effects of DE-induced oxidative stress in plasma and the thyroid, specifically examining how effects differ based on sex and a high-fat diet (HFD). We exposed male and female mice (low-density lipoprotein receptor knockout mice) to filtered air or DE for 18 weeks, while fed HFD or Chow. In plasma, we measured the activity of the antioxidant enzyme paraoxonase-1 (PON1) and the concentration of the acute-phase serum amyloid A (SAA) protein via ELISA. In thyroid tissue, we extracted RNA and used RNA-Seq to assess DE-induced transcriptional reprogramming. We expect that DE exposure will result in higher levels of inflammation (SAA) and lower levels of antioxidants (PON1). We expect that these effects will display sex differences and will be more pronounced in HFD-fed mice fed. Our transcriptomics analysis will help identify new genes and pathways affected by DE, diet, or both. Our results will improve our understanding of the link between air pollution and thyroid disorders, guiding future research and interventions to address the growing health concern of thyroid disorders and related noncommunicable diseases.

Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) is an emerging global human health concern and a risk factor for cardiovascular diseases and atherosclerosis. While the pathogenesis of MAFLD is complex and multifactorial, scientific evidence suggests environmental factors play a role in the development of the disease. Prior studies indicate exposure to particulate matter (PM) leads to MAFLD. A major constituent of ambient PM is diesel exhaust particles (DEPs). This study aims to explore the association between exposure to DEPs and the development of MAFLD using a murine model vulnerable to MAFLD development. DEPs cause oxidative stress through the generation of reactive oxygen species within the body. Male and female low-density lipoprotein receptor knockout mice were exposed to filtered air or freshly generated DE for 18 weeks while fed a high-fat or Chow diet. Plasma and liver tissue were harvested for biochemical measurements. The levels of a panel of lipid markers (triglycerides, cholesterol, free fatty acids) and glucose were measured in plasma and liver via colorimetric assay kits. Liver oxidative stress (8-isoprostane; nuclear factor erythroid 2-related factor 2, and 3-nitrotyrosine) was quantified via ELISA and Western blot (WB), respectively. Levels of peroxisome proliferator-activated receptor alpha (PPARα) were assessed via WB. We found statistically significant increases in plasma glucose and plasma and liver cholesterol in DE HFD male mice, and plasma triglycerides in DE HFD female mice. We expect to find increased liver oxidative stress and decreased liver PPARα protein, providing insight into the metabolic pathways associated with MAFLD that are disrupted by DE. Our findings will lead to a better understanding of air pollution as a risk factor for MAFLD and inform targeted interventions for affected populations.