Back to search

BEDREHELSE-Bedre helse og livskvalitet

Signaling Impairments GeNerated by Endocrine Disruptors.

Awarded: NOK 5.9 mill.

Environmental pollutants like persistent organic pollutants (POPs) are man-made chemicals that are omnipresent in our environment. We previously reported that POPs present in fatty fish (e.g. farmed Atlantic salmon) could contribute to insulin resistance, a hallmark of type 2 diabetes. We have now confirmed these findings in a human study performed in collaboration with Canadian researchers and clinicians. We found that obese women without insulin resistance and with low risk for type 2 diabetes and cardiovascular complications have lower plasma POP concentrations than obese women with insulin resistance. If confirmed in other populations, these findings may have important consequences for public health and for the treatment of metabolic disease. In parallel to these results we are now performing different studies to better understand the mechanistic modes of action of POPs as endocrine disruptors and obesogens in different in vivo and in vitro models.

Endocrine disruptors are chemicals that interfere with the body's endocrine system, thereby generating adverse effects. Recently, we demonstrated that persistent organic pollutants (POPs), which are omnipresent in our environment, could lead to insulin re sistance, a hallmark of type 2 diabetes (T2D) and obesity. The molecular mechanisms behind these harmful effects are currently unknown. SIGNED aims to understand how POPs, but also other endocrine disruptors like bisphenol A, can impair insulin action and affect glucose and lipid metabolism. To resolve this challenging task, this research proposal aims to explore the following questions: 1) Are there specific insulin-sensitive cells primarily affected by environmental pollutants? 2) How do pollutants affe ct insulin action when present as single compounds and as mixtures? 3) What are the dose-response effects of endocrine disruptors? 4) Which signaling pathways contribute to insulin resistance? SIGNED will apply an integrative and multi-tiered approach th at will combine cutting edge molecular techniques with metabolic phenotyping in order to understand how changes at protein and gene levels (phosphorylation, expression, miRNA, epigenetics) can explain changes in metabolic response to environmental polluta nts. First, the in vitro mechanistic modes of action of pollutants as single compounds and mixtures will be deciphered in different insulin sensitive cells. Then, we will transfer our in vitro knowledge to in vivo models, and explore the potential signall ing pathways regulated by endocrine disruptors. Altogether, SIGNED will contribute to discover novel and important cellular and molecular mechanisms by which endocrine disruptors can induce insulin resistance, thereby opening new directions for the preve ntion and treatment of metabolic diseases.

Funding scheme:

BEDREHELSE-Bedre helse og livskvalitet