Effect of chronic p,p'-dichlorodiphenyldichloroethylene (DDE) exposure on high fat diet-induced alterations in glucose and lipid metabolism in male C57BL/6H mice.
Effect of chronic p,p'-dichlorodiphenyldichloroethylene (DDE) exposure on high fat diet-induced alterations in glucose and lipid metabolism in male C57BL/6H mice.
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慢性P，P'-二氯二苯基氯乙烯（DDE）暴露对雄性C57BL/6H小鼠葡萄糖和脂质代谢的高脂肪饮食诱导的改变。
DOI：
10.1016/j.tox.2014.12.017
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发表时间：
2015-02-03
期刊：
影响因子：
4.5
通讯作者：
Chambers JE
中科院分区：
文献类型：
--
作者：
Howell GE 3rd;Mulligan C;Meek E;Chambers JE
糖尿病是一种非常普遍的代谢性疾病，影响了2910万人，占美国人口的9.3%。最常见的糖尿病形式是2型糖尿病（T2D），占所有报告的糖尿病病例的90-95%。虽然T2D的确切病因仍然是一个谜，但已知的风险因素包括年龄、体重、久坐的生活方式、不良的饮食习惯和遗传易感性。然而，这些危险因素并不能充分解释T2D患病率的增加。近年来，环境暴露作为潜在的危险因素被探讨。事实上，流行病学和有限的经验研究表明，某些持久性有机污染物（POPs）的血清浓度升高，包括p，p ' -二氯二苯三氯乙烷（DDT）、p,p ' -二氯二苯二氯乙烯（DDE）的生物蓄积性代谢物，与T2D患病率增加呈正相关。本研究的目的是确定长期暴露于DDE是否会促进高饱和脂肪喂养小鼠体内模型中的T2D。雄性C57BL/6H小鼠连续5天灌胃DDE （2.0 mg/kg）或载药（玉米油；1 ml/kg），然后在研究期间每7天一次。在连续5天给药后一周，动物被放置在低脂肪（10%卡路里来自猪油）或高脂肪（45%卡路里来自猪油）饮食（HFD）中，持续13周。长期暴露于DDE可促进HFD饮食4周和8周后的空腹高血糖，并在第13周使空腹血糖水平正常化。在第12周，dde介导的空腹高血糖降低之前，葡萄糖耐量有所改善。除了使高脂肪喂养结束时的空腹高血糖正常化外，DDE暴露还降低了hfd诱导的空腹高胰岛素血症、胰岛素抵抗的稳态模型评估（HOMA-IR）值和肝脏脂肪变性。因此，根据目前的数据，慢性DDE暴露似乎对雄性C57BL/6H小鼠HFD诱导的高血糖有双相影响，其特征是在摄入HFD的第4周和第8周空腹血糖升高，然后在牺牲后血糖正常。此外，慢性DDE暴露减少了牺牲后hfd诱导的肝脏脂肪变性。这些结果表明，长期暴露于DDE可以直接影响全身葡萄糖和肝脏脂质代谢，这些影响可能是饮食依赖的。
Diabetes mellitus is a highly prevalent metabolic disease affecting 29.1 million people or 9.3% of the population of the United States. The most prevalent form of diabetes is type 2 diabetes (T2D) which comprises 90–95% of all reported cases of diabetes. While the exact cause of T2D remains an enigma, known risk factors include age, weight, sedentary lifestyle, poor dietary habits, and genetic predisposition. However, these risk factors can not sufficiently explain the increasing prevalence of T2D. Recently, environmental exposures have been explored as potential risk factors. Indeed, epidemiological and limited empirical studies have revealed elevated serum concentrations of certain persistent organic pollutants (POPs), including the bioaccumulative metabolite of p,p′-dichlorodiphenyltrichloroethane (DDT), p,p′-dichlorodiphenyldichloroethylene (DDE), are positively correlated with increased T2D prevalence. The goal of the present study is to determine if chronic exposure to DDE promotes T2D in a widely used in vivo model, the high saturated fat-fed mouse. Male C57BL/6H mice were exposed to DDE (2.0 mg/kg) or vehicle (corn oil; 1 ml/kg) via gavage for 5 consecutive days, then every 7 days for the duration of the study. One week following the 5 day consecutive DDE dosing, animals were placed on either a low fat (10% kcal from lard) or high fat (45% kcal from lard) diet (HFD) for 13 weeks. Chronic exposure to DDE promoted fasting hyperglycemia after 4 and 8 weeks on the HFD diet and normalized fasting blood glucose levels at week 13. This DDE-mediated decrease in fasting hyperglycemia was preceded by improved glucose tolerance at week 12. In addition to normalizing fasting hyperglycemia at the end of high fat feeding, DDE exposure decreased HFD-induced fasting hyperinsulinemia, homeostasis model assessment of insulin resistance (HOMA-IR) values, and hepatic steatosis. Therefore, based on the current data, chronic DDE exposure appears to have a biphasic effect on HFD-induced hyperglycemia in the male C57BL/6H mouse characterized by elevated fasting blood glucose at weeks 4 and 8 of HFD intake followed by normoglycemia upon sacrifice. In addition, chronic DDE exposure reduced HFD-induced hepatic steatosis upon sacrifice. These results indicate chronic exposure to DDE can directly affect systemic glucose and hepatic lipid metabolism and that these effects can be diet dependent.
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影响因子：
3.7
作者：
Guo J;Jou W;Gavrilova O;Hall KD
通讯作者：
Hall KD
影响因子：
7.7
作者：
Biddinger, SB;Almind, K;Kahn, CR
通讯作者：
Kahn, CR
在四种常用的近交小鼠菌株中的体内葡萄糖代谢。
影响因子：
7.7
作者：
Berglund, Eric D.;Li, Candice Y.;Poffenberger, Greg;Ayala, Julio E.;Fueger, Patrick T.;Willis, Shannon E.;Jewell, Marybeth M.;Powers, Alvin C.;Wasserman, David H.
通讯作者：
Wasserman, David H.
影响因子：
10.4
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
通讯作者：
Frøyland L
DOI：
10.1097/mco.0b013e328342991c
发表时间：
2011-03
影响因子：
3.1
作者：
Jump DB
通讯作者：
Jump DB