Toxicology Letters 215 (2012) 8–15 Contents lists available at SciVerse ScienceDirect Toxicology Letters jou rn al h om epa ge: www.elsevier.com/locate/toxlet Metabolic impacts of high dietary exposure to persistent organic pollutants in mice  Mohammad Madani Ibrahim a,b , Even Fjære a,c , Erik-Jan Lock a , Livar Frøyland a , Niels Jessen d , Sten Lund e , Hubert Vidal f , Jérôme Ruzzin a,g,∗ a National Institute of Nutrition and Seafood Research, Postboks 2029, 5817 Bergen, Norway b Institute of Biomedicine, University of Bergen, Postboks 7804, 5020 Bergen, Norway c Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen, Denmark d Aarhus University Hospital, Research Laboratory for Biochemical Pathology, DK-8000 Aarhus, Denmark e Aarhus University Hospital, Department of Internal Medicine and Diabetes and Institute of Experimental Clinical Research, DK-8000 Aarhus, Denmark f INSERM U-1060, INRA U-1235, Lyon 1 University and CarMeN Laboratory, F-69921 Oullins, France g Department of Biology, University of Bergen, Postboks 7803, 5020 Bergen, Norway h i g h l i g h t s ◮ Persistent organic pollutants are potent endocrine disruptors. ◮ Elevated dietary exposure to POPs reduced body weight gain in mice. ◮ Despite elevated POP accumulation, mice remained sensitive to insulin. ◮ Nutrition may modulate the toxicity of environmental pollutants. a r t i c l e i n f o Article history: Received 6 June 2012 Received in revised form 24 September 2012 Accepted 26 September 2012 Available online 4 October 2012 Keywords: Endocrine disruptors Metabolic syndrome Type 2 diabetes Pollution Xenobiotics Marine food a b s t r a c t Persistent organic pollutants (POPs) have been linked to metabolic diseases. Yet, the effects of high exposure to dietary POPs remain unclear. We therefore investigated whether elevated exposure to POPs provided by whale meat supplementation could contribute to insulin resistance. C57BL/6J mice were fed control (C) or very high-fat diet (VHF) containing low or high levels of POPs (VHF +POPs ) for eight weeks. To elevate the dietary concentrations of POPs, casein was replaced by whale meat containing high levels of pollutants. Feeding VHF +POPs induced high POP accumulation in the adipose tissue of mice. However, compared with VHF-fed mice, animals fed VHF +POPs had improved insulin sensitivity and glucose tolerance, and reduced body weight. Levels of ectopic fat in skeletal muscles and liver were reduced in mice fed VHF +POPs . These mice also gained less adipose tissue and had a tendency to reduced energy intake. In pair-feeding experiments, improved insulin action and reduced body weight gain were still observed in VHF +POPs compared to VHF pair-fed mice. We concluded that mice fed VHF contaminated with POPs derived from whale meat remain sensitive to insulin and glucose tolerant despite significant body burden of POPs. This indicates complex interactions between organic pollutants and nutrition in the development of metabolic disorders. © 2012 Elsevier Ireland Ltd. All rights reserved. Abbreviations: ANOVA, analysis of variance; C, control diet; DDTs, dichloro-diphenyl-trichloroethanes; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; VHF, high-fat diet; VHF+POPs , high-fat diet containing high levels of POPs; HxCDD, hexachlorodibenzo-p-dioxin; ip, intraperitoneal; LSD, least-square difference; n-3 PUFAs, n-3 polyunsaturated fatty acids; PCBs, polychlorinated biphenyls; POPs, persistent organic pollutants; TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin; TAG, triacylglycerols.  Funding sources: JR and MMI were supported by the Research Council of Norway (#204473 and #185567, respectively). EF was supported by the Danish Council for Strategic Research (#2101-08-0053). ∗ Corresponding author at: Department of Biology, University of Bergen, Postboks 7803, 5020 Bergen, Norway. Tel.: +47 55584400; fax: +47 55584450. E-mail address: jerome.ruzzin@bio.uib.no (J. Ruzzin). 0378-4274/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.toxlet.2012.09.022