Center for Integrative Toxicology, Michigan State University, East Lansing, Michigan, USA.
J Toxicol Environ Health A. 2011;74(10):658-67. doi: 10.1080/15287394.2011.539119.
The potential for the obese state to alter sensitivity to toxic chemicals is poorly understood. In this study, dose-response effects of the trichothecene deoxynivalenol (DON), a common food-borne mycotoxin, were determined on body weight of diet-induced obese mice. In study 1, the effects of feeding adult female B6C3F1 mice a high-fat diet (HFD; 60% kcal from fat) containing 0, 2, 5, or 10 ppm DON for 10 wk on body weight and adiposity were compared. Mice consuming 5 or 10 ppm DON exhibited a 15 and 24% decrease in weight gain and a 50 and 83% reduction in periuterine fat, respectively. In study 2, mice were fed HFD for 8 wk to induce obesity and the effects of consuming HFD + 0, 2, 5, or 10 ppm DON for 8 wk were then determined. Mice fed 5 or 10 ppm DON exhibited a 16 and 23% weight reduction and a 0 and 40% periuterine fat reduction, respectively. In a follow-up experiment, food consumption was measured prior to and after the transition from HFD to HFD + 10 ppm DON. Exposure to DON was found to lower HFD consumption within 1 d, with significant weight loss in DON-fed mice evident after 6 d. In both studies 1 and 2, consumption of 5 or 10 ppm DON diminished circulating levels of insulin-like growth factor acid-labile subunit. Taken together, DON consumption lowered weight gain and produced weight loss in diet-induced obese mice at higher thresholds than that observed previously in normal B6C3F1 mice.
肥胖状态改变对有毒化学物质敏感性的潜力尚未被充分理解。在这项研究中,我们确定了常见的食物源性真菌毒素脱氧雪腐镰刀菌烯醇(DON)对饮食诱导肥胖小鼠体重的剂量-反应效应。在研究 1 中,比较了成年雌性 B6C3F1 小鼠连续 10 周喂食高脂肪饮食(HFD;脂肪提供 60%的热量)并添加 0、2、5 或 10 ppm DON 对体重和肥胖的影响。摄入 5 或 10 ppm DON 的小鼠体重增加分别减少了 15%和 24%,围生脂肪减少了 50%和 83%。在研究 2 中,小鼠先喂食 HFD 8 周以诱导肥胖,然后再喂食 HFD + 0、2、5 或 10 ppm DON 8 周。喂食 5 或 10 ppm DON 的小鼠体重分别减轻了 16%和 23%,围生脂肪减少了 0%和 40%。在后续实验中,测量了从 HFD 转换为 HFD + 10 ppm DON 前后的食物消耗。发现 DON 暴露会在 1 天内降低 HFD 的摄入量,DON 喂养的小鼠在 6 天后体重明显减轻。在研究 1 和 2 中,5 或 10 ppm DON 的摄入降低了循环胰岛素样生长因子酸不稳定亚基水平。综上所述,与之前在正常 B6C3F1 小鼠中观察到的情况相比,DON 摄入降低了饮食诱导肥胖小鼠的体重增加,并导致体重减轻,阈值更高。