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.
  
  
  CONCLUSIONS
  Our findings provide evidence that exposure to POPs commonly present in food chains leads to insulin resistance and associated metabolic disorders.
authors.affiliation: National Institute of Nutrition and Seafood Research (NIFES), Bergen, Norway. jerome.ruzzin@nifes.no
authors.forename: Jérôme
authors.initials: J
authors.lastname: Ruzzin
authors.forename: Rasmus
authors.initials: R
authors.lastname: Petersen
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Meugnier
authors.forename: Lise
authors.initials: L
authors.lastname: Madsen
authors.forename: Erik-Jan
authors.initials: EJ
authors.lastname: Lock
authors.forename: Haldis
authors.initials: H
authors.lastname: Lillefosse
authors.forename: Tao
authors.initials: T
authors.lastname: Ma
authors.forename: Sandra
authors.initials: S
authors.lastname: Pesenti
authors.forename: Si Brask
authors.initials: SB
authors.lastname: Sonne
authors.forename: Troels Torben
authors.initials: TT
authors.lastname: Marstrand
authors.forename: Marian Kjellevold
authors.initials: MK
authors.lastname: Malde
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Du
authors.forename: Carine
authors.initials: C
authors.lastname: Chavey
authors.forename: Lluis
authors.initials: L
authors.lastname: Fajas
authors.forename: Anne-Katrine
authors.initials: AK
authors.lastname: Lundebye
authors.forename: Christian Lehn
authors.initials: CL
authors.lastname: Brand
authors.forename: Hubert
authors.initials: H
authors.lastname: Vidal
authors.forename: Karsten
authors.initials: K
authors.lastname: Kristiansen
authors.forename: Livar
authors.initials: L
authors.lastname: Frøyland
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D050260:Carbohydrate Metabolism / Q000187:drug effects; D004785:Environmental Pollutants / Q000633:toxicity*; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D006843:Hydrocarbons, Chlorinated / Q000633:toxicity; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D024821:Metabolic Syndrome / Q000139:chemically induced / Q000378:metabolism; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D010575:Pesticides / Q000633:toxicity; D016133:Polymerase Chain Reaction; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004785:Environmental Pollutants; D006843:Hydrocarbons, Chlorinated; D010575:Pesticides; D005947:Glucose