Transcript – The Role of MALAT1 and Nrf2 in Regulating Diabetogenic Effects of Early Life Air Pollution Exposure

Our T3 project investigated how early life exposure to particulate matter air pollution may predispose offshoring to developing Type two diabetes, and if so, what were the major pathways involved? Specifically, our project looked at the role of ultrafine particles. These tiny nano sized particles are known to cross the placenta and cause downstream inflammation and oxidative stress. The nerve to antioxidant response pathway plays an important role in response to PPM induced oxidative stress, as well as insulin resistance and Type two diabetes. Therefore, we used our established mouse model to investigate how offspring may develop metabolic disease over the course of 15 weeks. While we did not see any changes in insulin levels or glucose levels, we did find a sustained growth, inhibitory effect and male and female offspring. This corresponded to a significant early decrease in fetal links and body weight, which was evident in mice lacking in AFTA or the ability to respond to oxidative stress from this in utero PMB exposure. Alternatively, in mice that lacked Malat1, the negative repressor of NRF too, we did seem to see some sort of mitigation of the adverse effects Manuscript’s detailing. These findings are under review, and future work will explore the impact on growth, suppression and bone health, as well as promote policy for changes to protect children’s health.