Persistent organic pollutant exposure leads to insulin resistance syndrome.
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.
Ruzzin
Jérôme
J
National Institute of Nutrition and Seafood Research (NIFES), Bergen, Norway. jerome.ruzzin@nifes.no
Petersen
Rasmus
R
Meugnier
Emmanuelle
E
Madsen
Lise
L
Lock
Erik-Jan
EJ
Lillefosse
Haldis
H
Ma
Tao
T
Pesenti
Sandra
S
Sonne
Si Brask
SB
Marstrand
Troels Torben
TT
Malde
Marian Kjellevold
MK
Du
Zhen-Yu
ZY
Chavey
Carine
C
Fajas
Lluis
L
Lundebye
Anne-Katrine
AK
Brand
Christian Lehn
CL
Vidal
Hubert
H
Kristiansen
Karsten
K
Frøyland
Livar
L
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
D004785:Environmental Pollutants; D006843:Hydrocarbons, Chlorinated; D010575:Pesticides; D005947:Glucose