National Institute of Nutrition and Seafood Research (NIFES), Bergen, Norway.
Environ Health Perspect. 2010 Apr;118(4):465-71. doi: 10.1289/ehp.0901321. Epub 2009 Nov 19.
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.
We investigated whether exposure to POPs contributes to insulin resistance and metabolic disorders.
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.
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.
Our findings provide evidence that exposure to POPs commonly present in food chains leads to insulin resistance and associated metabolic disorders.
胰岛素抵抗综合征的发病率在全球范围内以惊人的速度增长，这对 21 世纪的公共卫生保健构成了严重挑战。最近，流行病学研究将 2 型糖尿病的患病率与持久性有机污染物（POPs）的升高的体内负荷联系起来。然而，缺乏实验证据表明 POPs 与胰岛素抵抗的发展之间存在因果关系。
我们研究了接触 POPs 是否会导致胰岛素抵抗和代谢紊乱。
通过食用含有来自养殖大西洋鲑鱼的精炼或粗鱼油的高脂肪饮食，使 Sprague-Dawley 大鼠在 28 天内接触亲脂性 POPs。此外，分化的脂肪细胞还暴露于几种模拟粗鱼油中存在的有机污染物相对丰度的 POP 混合物中。我们测量了体重、全身胰岛素敏感性、POP 积累、脂质和葡萄糖稳态以及基因表达，并进行了微阵列分析。
暴露于粗鲑鱼油但不是精炼鲑鱼油的成年雄性大鼠出现胰岛素抵抗、腹部肥胖和肝脂肪变性。在培养的脂肪细胞中，POP 特别是有机氯农药，导致胰岛素作用明显抑制，证实了 POP 对胰岛素抵抗的贡献。此外，POP 诱导了胰岛素诱导基因-1（Insig-1）和 Lpin1 的下调，这两种基因是脂质稳态的主要调节剂。
我们的研究结果提供了证据，表明暴露于食物链中常见的 POPs 会导致胰岛素抵抗和相关的代谢紊乱。
