Persistent organic pollutant exposure leads to insulin resistance syndrome.

Abstract

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:

Sprague-Dawley rats were exposed for 28 days to lipophilic POPs through the consumption of a high-fat diet containing either refined or crude fish oil obtained from farmed Atlantic salmon. In addition, 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, and gene expression and we 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, two master regulators of lipid homeostasis.

CONCLUSION:

Our findings provide evidence that exposure to POPs commonly present in food chains leads to insulin resistance and associated metabolic disorders.

• Authors: Jérôme Ruzzin, Rasmus Petersen, Emmanuelle Meugnier, Lise Madsen, Erik-Jan Lock, Haldis Lillefosse, Tao Ma, Sandra Pesenti, Si Brask Sonne, Troels Torben Marstrand, Marian Kjellevold Malde, Zhen-Yu Du, Carine Chavey, Lluis Fajas, Anne-Katrine Lundebye, Christian Lehn Brand, Hubert Vidal, Karsten Kristiansen, Livar Frøyland
• Journal: Environmental health perspectives (Environ Health Perspect) Vol. 118 Issue 4 Pg. 465-71 (Apr 2010) ISSN: 1552-9924 [Electronic] United States
• PMID: 20064776 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Environmental Pollutants
• Hydrocarbons, Chlorinated
• Pesticides
• Glucose

Topics

• 3T3-L1 Cells
• Animals
• Carbohydrate Metabolism (drug effects)
• Environmental Pollutants (toxicity)
• Glucose (metabolism)
• Glucose Clamp Technique
• Hydrocarbons, Chlorinated (toxicity)
• Insulin Resistance
• Lipid Metabolism (drug effects)
• Male
• Metabolic Syndrome (chemically induced, metabolism)
• Mice
• Oligonucleotide Array Sequence Analysis
• Pesticides (toxicity)
• Polymerase Chain Reaction
• Rats
• Rats, Sprague-Dawley