Persistent organic pollutant exposure leads to insulin resistance syndrome.
Persistent organic pollutant exposure leads to insulin resistance syndrome.
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DOI：
10.1289/ehp.0901321
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发表时间：
2010-04
影响因子：
10.4
通讯作者：
Frøyland L
中科院分区：
文献类型：
--
作者：
Ruzzin J;Petersen R;Meugnier E;Madsen L;Lock EJ;Lillefosse H;Ma T;Pesenti S;Sonne SB;Marstrand TT;Malde MK;Du ZY;Chavey C;Fajas L;Lundebye AK;Brand CL;Vidal H;Kristiansen K;Frøyland L
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加，给21世纪的公共卫生保健带来了严峻的挑战。最近，流行病学研究发现 2 型糖尿病的患病率与体内持久性有机污染物 (POP) 负担增加有关。然而，缺乏证明持久性有机污染物与胰岛素抵抗之间存在因果关系的实验证据。我们研究了接触持久性有机污染物是否会导致胰岛素抵抗和代谢紊乱。 Sprague-Dawley 大鼠通过食用含有从养殖大西洋鲑鱼中提取的精制或粗制鱼油的高脂肪饮食，暴露于亲脂性持久性有机污染物 28 天。此外，分化的脂肪细胞暴露于几种 POP 混合物中，这些混合物模拟了粗鲑鱼油中有机污染物的相对丰度。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。接触粗制而非精制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。持久性有机污染物对胰岛素抵抗的贡献在培养的脂肪细胞中得到证实，其中持久性有机污染物，特别是有机氯农药，会导致胰岛素作用的强烈抑制。此外，POPs 还会导致胰岛素诱导基因 1 (Insig-1) 和 Lpin1（脂质稳态的两个主要调节因子）的下调。我们的研究结果证明，接触食物链中常见的持久性有机污染物会导致胰岛素抵抗和相关代谢紊乱。
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.
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影响因子：
7.7
作者：
Cani, Patrice D.;Amar, Jacques;Burcelin, Remy
通讯作者：
Burcelin, Remy
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影响因子：
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作者：
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通讯作者：
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作者：
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通讯作者：
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作者：
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通讯作者：
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影响因子：
56.9
作者：
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通讯作者：
Schwager, SJ