Abstract
BACKGROUND: Obesity is a chronic metabolic disease responsible for causing various health problems. Obese individuals experience disrupted homeostasis, thus making them more vulnerable to environmental pollutants. This study investigated the effect of pre-existing obesity on respiratory toxicity and explored whether sex differences exist in the response to titanium dioxide nanoparticles (TiO(2)-NPs), a component of air pollutants. METHODS: Male and female mice were fed a normal diet (ND) or a high-fat diet (HFD) for 26 weeks and then intratracheally instilled with TiO(2)-NPs at concentrations of 0, 0.1, 0.2, and 0.4 mg/50 μL on days 1, 4, 6, 9, 11, and 13. Mice were sacrificed 24 h after the final administration. RESULTS: In HFD-fed obese mice, TiO(2)-NPs exposure led to respiratory inflammation through the toll-like receptor 4-mediated mitogen-activated protein kinase signaling pathway and a subsequent inflammatory response induced by oxidative stress. These effects were more pronounced in females than in males, and this was attributed to the higher sensitivity of females to HFD consumption and early depletion of antioxidant defenses. CONCLUSION: Our findings suggest an increased risk of respiratory toxicity in individuals with pre-existing obesity and highlight that these effects are sex-specific.