The impact of perinatal exposure to perfluoroalkyl acids, and its linkage to predisposition of metabolic disorders in adult offspring (PI: Professor Chris Wong)
Endocrine disrupting chemicals (EDCs) have been shown to cause long-term effects on animal health and development. Emerging evidence suggests that endocrine disruption that are caused by pollutants is directly linked to “the developmental basis of adult disease”, leading to the predisposition for disease or organ dysfunction. The incidence of obesity, diabetes and fatty liver diseases has become highly prevalent globally, but the possible underlying mechanistic action on how EDC’s predispose humans to these metabolic disorders is still a clear mystery. Epidemiological studies in numerous disasters have suggested the link between pollutant exposure to disturbed glucose homeostasis, metabolic syndrome and insulin resistance. Numerous laboratory animal studies have also shown that exposure of mice to the fluorinated compounds (perfluoroalkyl acids, PFAAs) can result in the development of metabolic disorder. However a lot more needs to be done to understand the mechanistic actions involved.
PFAAs are persistent in the environment, ubiquitous to the general public and have a long serum elimination half-life in animals. The notorious member of PFAAs, perfluorooctane sulfonate (PFOS) is prioritized as a global concerning chemical at the Stockholm Convention in 2009, due to its serious harmful effects in mammals and aquatic organisms. Industrial production of PFOS has already been phased out in most countries in 2002, except in China where it’s still manufactured and widely used today. In our region, PFAA contamination has been reported in the environment (i.e. water and dust), food and human blood samples, implying the exposure risk of our population to PFAAs. In this proposal, we plan to pin down the molecular targets of PFAA and the associated hormonal and metabolic changes in PFAA-elicited metabolic syndromes, which would help to significantly further our understanding on the non-genetic causes /origin of these metabolic diseases.
We will combine molecular, metabolomics and physiological approaches to obtain multiple lines of evidence to identify the molecular targets of PFAAs as well as the consequential molecular fingerprints in blood serum and liver extracts. Using perinatal animal exposure models, the underlying mechanistic actions of PFAAs to adipocytes, pancreatic islets and liver physiology will be deciphered. The findings of this study will help to evaluate the risk of public exposure to PFAAs and its underlying mechanistic actions on human health. This understanding will provide insight for the respective policy makers to devise the appropriate remedial strategies, hence providing long term benefits to the community.