The prevalence of childhood obesity has increased at an alarming rate from 4% in 1975 to 18% in 2016 globally. Obese children are likely to stay obese through adolescence and into adulthood and are at a higher risk to develop cardiometabolic diseases and cancer. Current prevention strategies, including interventions on well-known risk factors such as unhealthy diet and sedentary behavior, have not successfully reversed the increasing trend in obesity prevalence. Increasing evidence suggests that early-life air pollution exposures may have a lifelong impact on the development of many chronic diseases including obesity.
Metabolomics studies in human have also shown that exposures to particulate matter and traffic-related pollutants were associated with dysregulated amino acid and fatty acid metabolism, which have been linked to the etiology of obesity and insulin resistance.
No published metabolomics studies have examined the contributions of long-term regional AP and NRAP exposures to metabolic disruptions, especially in children. Additionally, the mechanisms underlying the impact of AP-related metabolomic signatures on adiposity and diabetes traits are largely unknown.
Taken together, I hypothesize that long-term exposures to regional AP and NRAP affect obesity and type 2 diabetes traits through changes in key metabolic pathways, reflected by metabolomic signatures. The impacts of AP exposures on childhood obesity and metabolic disruption may begin in the prenatal period, and continue throughout childhood. Additionally, I hypothesize that the mechanisms linking AP, metabolomic signatures, adiposity and diabetes traits may involve inflammatory activation and leptin resistance.
In the next R00 project, I will apply my expertise in the MADRES study to examine the mechanism linking in utero air pollution exposures and low birth weight, while accounting for the influence by potential confounders and effect modifiers such as socio-demographic factors, maternal diet, and physical activity during pregnancy.
This work will fill a critical gap by providing scientific evidence for early-life impacts of in utero air pollution exposures on fetal programming of obesity by investigating metabolic perturbations induced by air pollution exposures in pregnant women and newborns. Findings from this project will help to reveal novel molecular targets for early intervention and prevention of new-onset obesity and metabolic dysfunction.
Another take on this topic are per- and polyfluoroalkyl substances (PFASs) exposures. PFASs are ubiquitous among the US population and has been linked to adverse health outcomes including cardiometabolic diseases, immune dysregulation and endocrine disruption. However, the metabolic mechanism underlying the adverse health effect of PFASs exposure is unknown.
Targeted metabolomics analysis indicated that higher PFOA exposure was associated with higher levels of glycerol, which itself was associated with higher 30-minute glucose.
Increased lipolysis and fatty acid oxidation could contribute to the biological mechanisms linking PFAS exposure and impaired glucose metabolism among young adults. Findings of this study warrants future experimental studies and epidemiological studies with larger sample size to replicate.
Chen Z, Yang T, Walker DI, et al. Dysregulated lipid and fatty acid metabolism link perfluoroalkyl substances exposure and impaired glucose metabolism in young adults. Environment International. 2020 Dec;145:106091. DOI: 10.1016/j.envint.2020.106091. PMID: 32892005; PMCID: PMC800