Persistent Organic Pollutant Exposure Leads to Insulin Resistance Syndrome

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; Livar Frøyland

doi:10.1289/ehp.0901321

Persistent Organic Pollutant Exposure Leads to Insulin Resistance Syndrome

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, Livar Frøyland

270 Citations (Scopus)

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.

Original language	English
Journal	Environmental Health Perspectives
Volume	118
Issue number	4
Pages (from-to)	465-71
ISSN	0091-6765
DOIs	https://doi.org/10.1289/ehp.0901321
Publication status	Published - Apr 2010

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Ruzzin, J., Petersen, R., Meugnier, E., Madsen, L., Lock, E-J., Lillefosse, H., Ma, T., Pesenti, S., Sonne, S. B., Marstrand, T. T., Malde, M. K., Du, Z-Y., Chavey, C., Fajas, L., Lundebye, A-K., Brand, C. L., Vidal, H., Kristiansen, K., & Frøyland, L. (2010). Persistent Organic Pollutant Exposure Leads to Insulin Resistance Syndrome. Environmental Health Perspectives, 118(4), 465-71. https://doi.org/10.1289/ehp.0901321

Ruzzin, J, Petersen, R, Meugnier, E, Madsen, L, Lock, E-J, Lillefosse, H, Ma, T, Pesenti, S, Sonne, SB, Marstrand, TT, Malde, MK, Du, Z-Y, Chavey, C, Fajas, L, Lundebye, A-K, Brand, CL, Vidal, H, Kristiansen, K & Frøyland, L 2010, 'Persistent Organic Pollutant Exposure Leads to Insulin Resistance Syndrome', Environmental Health Perspectives, vol. 118, no. 4, pp. 465-71. https://doi.org/10.1289/ehp.0901321

@article{cf8495e017b011df8ed1000ea68e967b,

title = "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.",

author = "J{\'e}r{\^o}me Ruzzin and Rasmus Petersen and Emmanuelle Meugnier and Lise Madsen and Erik-Jan Lock and Haldis Lillefosse and Tao Ma and Sandra Pesenti and Sonne, {Si Brask} and Marstrand, {Troels Torben} and Malde, {Marian Kjellevod} and Zhen-Yu Du and Carine Chavey and Lluis Fajas and Anne-Katrine Lundebye and Brand, {Christian Lehn} and Hubert Vidal and Karsten Kristiansen and Livar Fr{\o}yland",

note = "Keywords: contaminants, farmed salmon, metabolic syndrome, nonalcoholic fatty liver, obesity, pollution, public health, type 2 diabetes",

year = "2010",

month = apr,

doi = "10.1289/ehp.0901321",

language = "English",

volume = "118",

pages = "465--71",

journal = "Environmental Health Perspectives",

issn = "0091-6765",

publisher = "National Institute of Environmental Health Sciences",

number = "4",

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TY - JOUR

T1 - Persistent Organic Pollutant Exposure Leads to Insulin Resistance Syndrome

AU - Ruzzin, Jérôme

AU - Petersen, Rasmus

AU - Meugnier, Emmanuelle

AU - Madsen, Lise

AU - Lock, Erik-Jan

AU - Lillefosse, Haldis

AU - Ma, Tao

AU - Pesenti, Sandra

AU - Sonne, Si Brask

AU - Marstrand, Troels Torben

AU - Malde, Marian Kjellevod

AU - Du, Zhen-Yu

AU - Chavey, Carine

AU - Fajas, Lluis

AU - Lundebye, Anne-Katrine

AU - Brand, Christian Lehn

AU - Vidal, Hubert

AU - Kristiansen, Karsten

AU - Frøyland, Livar

N1 - Keywords: contaminants, farmed salmon, metabolic syndrome, nonalcoholic fatty liver, obesity, pollution, public health, type 2 diabetes

PY - 2010/4

Y1 - 2010/4

N2 - 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.

AB - 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.

U2 - 10.1289/ehp.0901321

DO - 10.1289/ehp.0901321

M3 - Journal article

C2 - 20064776

SN - 0091-6765

VL - 118

SP - 465

EP - 471

JO - Environmental Health Perspectives

JF - Environmental Health Perspectives

IS - 4

ER -

Persistent Organic Pollutant Exposure Leads to Insulin Resistance Syndrome

Abstract

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