Molecular mechanisms induced by air pollution and obesity over the life course

Abstract

According to the World Health Organization, nearly one in four of total global deaths is due to modifiable environmental stressors. Even before birth environmental exposures influence the onset and progression of chronic diseases later in life, which is referred to as the “Barker” or “Developmental Origins of Health and Disease” (DOHaD) hypothesis. Among the most harmful environmental risk factors are ambient particulate matter (PM) exposure and excess body fat. In Belgium, almost half of the population suffers from overweight and around 14% is obese. Since the mechanisms driving environmental exposure-induced adverse health effects are poorly understood, in this doctoral dissertation, we tried to further elucidate underlying biochemical pathways by means of hypothesis-driven and hypothesis-generating approaches. We focused on mitochondrial DNA (mtDNA) content and telomere length, two molecular biomarkers of oxidative stress and inflammation. We furthermore implemented transcriptomic analyses to create new hypotheses concerning a biologically plausible link between PM exposure and adverse health effects. The specific objectives of this doctoral dissertation were: 1. To investigate the effect of maternal PM10 exposure during pregnancy on birth weight and small-for-gestational-age 2. To assess sex-specific transcriptomic responses to particulate air pollution exposure in newborns and in adults 3. To explore the sex-specific cross-sectional and longitudinal association of peripheral blood telomere length and mtDNA content with two obesity measures in a general adult population 4. To analyze the association between peripheral blood mtDNA content and long-term PM2.5 exposure in a general adult population Findings of this PhD project contribute to the international research investigating the impact of excess body fat and the impact of ambient PM at current exposure levels on human health. Promoting healthy weight by encouraging healthy food and physical activity in daily life, and lowering PM exposure below the WHO guidelines will help to reduce chronic diseases and mortality rates worldwide.