Persistent Organic Pollutant Exposure Leads to Insulin Resistance Syndrome

• Published in: Environmental Health Perspectives
• Main Authors: Ruzzin, Jérôme, Petersen, Rasmus, Fouilloux-Meugnier, Emmanuelle, Madsen, Lise, Lock, Erik-Jan, Lillefosse, Haldis, Ma, Tao, Pesenti, Sandra, Sonne, Si Brask, Ma, Troels Torben, Malde, Marian Kjellevold, Du, Zhen-Yu, Chavey, Carine, Fajas, Lluis, Lundebye, Anne-Katrine, Lehn Brand, Christian, Vidal, Hubert, Kristiansen, Karsten, Frøyland, Livar
• Other Authors: National Institute of Nutrition and Seafood Research (NIFES), Department of Biochemistry and Molecular Biology, University of Southern Denmark (SDU), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratory of Genomics and Molecular Biomedicine, Department of Biology, Department of Biology Copenhagen, Faculty of Science Copenhagen, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH)-Faculty of Science Copenhagen, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Simula Research Laboratory Lysaker (SRL), Laboratory of Aquaculture Nutrition and Environmental Health (LANEH), School of Life Sciences Shanghai, Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (UCPH)
• Format: Article in Journal/Newspaper
• Language: English
• Published: HAL CCSD 2010
• Subjects: Contaminants; farmed salmon; metabolic syndrome; nonalcoholic fatty liver; obesity; pollution; public health; type 2 diabetes; [SDV]Life Sciences [q-bio]; [SDV.EE.SANT]Life Sciences [q-bio]/Ecology; environment/Health; [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie; Sion; Atlantic salmon
• Online Access: https://hal.archives-ouvertes.fr/hal-01982018; https://hal.archives-ouvertes.fr/hal-01982018/document; https://hal.archives-ouvertes.fr/hal-01982018/file/ehp.0901321.pdf; https://doi.org/10.1289/ehp.0901321

International audience 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, epide-miological 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 meta-bolic disorders. Methods: Sprague-Dawley rats were exposed for 28 days to lipophilic POPs through the con-sumption 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 expres-sion and we performed micro array analysis. Results: Adult male rats exposed to crude, but not refined, salmon oil developed insulin resis-tance, 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