BACKGROUND: The incidence of the insulin resistance syndrome has increased at an
alarming rate worldwide creating a serious challenge to public health care in the 21st
century. Recently, epidemiological studies have associated the prevalence of type 2
diabetes with elevated body burdens of persistent organic pollutants (POPs). However,
experimental evidence demonstrating a causal link between POPs and the development
of insulin resistance is lacking.
OBJECTIVE: We investigated whether exposure to POPs contributes to insulin
resistance and metabolic disorders.
METHODS: Wistar rats were exposed for 28 days to lipophilic POPs through the
consumption of high-fat diet containing either refined or crude fish oil obtained from
farmed Atlantic salmon. Furthermore, differentiated adipocytes were exposed to several
POP mixtures that mimicked the relative abundance of organic pollutants present in
crude salmon oil. We measured body weight, whole-body insulin sensitivity, POP
accumulation, lipid and glucose homeostasis, gene expression and performed
microarray analysis.
RESULTS: Adult male rats exposed to crude, but not refined, salmon oil developed
insulin resistance, abdominal obesity and hepatosteatosis. The contribution of POPs to
insulin resistance was confirmed in cultured adipocytes where POPs, especially
organochlorine pesticides, led to robust inhibition of insulin action. Moreover, POPs
induced down-regulation of insulin-induced gene-1 (Insig-1) and Lpin1 genes, two
master regulators of lipid homeostasis.
CONCLUSION: Our findings, for the first time, provide evidence that exposure to
POPs commonly present in food chains leads to insulin resistance and associated
metabolic disorders.