Persistent Organic Pollutant Exposure Leads to Insulin Resistance Syndrome
http://ehp.niehs.nih.gov/docs/2009/0901321/abstract.html
Jérôme Ruzzin, Rasmus Petersen, Emmanuelle Meugnier, Lise Madsen, Erik-Jan Lock, Haldis Lillefosse, Tao Ma, Sandra Pesenti, Si Brask Sonne, Troels Torben Marstrand, Marian Kjellevod Malde, Zhen-Yu Du, Carine Chavey, Lluis Fajas, Anne-Katrine Lundebye, Christian Lehn Brand, Hubert Vidal, Karsten Kristiansen, and Livar Frøyland
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: 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.
Abstract
Abstract in PDF
This EHP-in-Press article has been peer-reviewed, revised, and accepted for publication. The EHP-in-Press articles are completely citable using the assigned DOI code for the article. This document will be replaced with the copyedited and formatted version as soon as it is available. Through the DOI number used in the citation, you will be able to access this document at each stage of the publication process. Environ Health Perspect doi:10.1289/ehp.0901321 available via http://dx.doi.org/ [Online 19 November 2009]
The full version of this article is available for free in PDF format.
http://ehp.niehs.nih.gov/docs/2009/0901321/abstract.html
Jérôme Ruzzin, Rasmus Petersen, Emmanuelle Meugnier, Lise Madsen, Erik-Jan Lock, Haldis Lillefosse, Tao Ma, Sandra Pesenti, Si Brask Sonne, Troels Torben Marstrand, Marian Kjellevod Malde, Zhen-Yu Du, Carine Chavey, Lluis Fajas, Anne-Katrine Lundebye, Christian Lehn Brand, Hubert Vidal, Karsten Kristiansen, and Livar Frøyland
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: 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.
Abstract
Abstract in PDF
This EHP-in-Press article has been peer-reviewed, revised, and accepted for publication. The EHP-in-Press articles are completely citable using the assigned DOI code for the article. This document will be replaced with the copyedited and formatted version as soon as it is available. Through the DOI number used in the citation, you will be able to access this document at each stage of the publication process. Environ Health Perspect doi:10.1289/ehp.0901321 available via http://dx.doi.org/ [Online 19 November 2009]
The full version of this article is available for free in PDF format.
