Fluoride Intensifies Hypercaloric Diet-Induced ER Oxidative Stress and Alters Lipid Metabolism

The role of fluoride (F) in oxidative stress is well reported, but its effects on the lipid metabolism has not been completely explored
Background
Here, we evaluated the relationship of diet and F-induced oxidative stress to lipid metabolism in the liver of rats eating normocaloric or hypercaloric diets for two time periods (20 or 60 days).
Methods
Seventy-two 21-day-old Wistar rats were divided into 2 groups (n = 36) based on the type of diet they were eating; each of these groups was then further divided into another two groups (n = 18) based on the time periods of either 20 or 60 days, for a total of four groups. Each of these was divided into 3 subgroups (n = 6 animals/subgroup), dependent on the dose of F administered in the drinking water (0 mg/L(control), 15 mg/L or 50 mg/L). After the experimental period, blood samples and the liver were collected. Plasma samples were analyzed for HDL, cholesterol and triglycerides. Western blots were performed to probe for GRP78, Erp29, SOD2, Apo-E and SREBP in hepatic tissues.
Results
As expected,the expression of target proteins involved in oxidative stress increased in the F-treated groups, especially in liver tissue obtained from animals eating a hypercaloric diet. Most changes in the lipid levels and pathological conditions were seen earlier in the time period, at day 20. The morphometric analyses showed a reduction in steatosis in groups on ahypercaloric diet and treated with 50 mg F/L compared to the control, while no changes were obtained in normocaloric-fed rats. Accordingly, plasma TG was reduced in the F-treated group. The reduced expression of Apo-E in a time- and diet-dependent pattern may account for the particular decrease in steatosis in hypercaloric-fed F-treated rats.
Conclusions
These results suggest that F changes liver lipid homeostasis, possibly because of the induction of oxidative stress, which seems to be higher in animals fed hypercaloric diets.

氟（Fluoride, F）在氧化应激中的作用已有充分报道，但其对脂质代谢的影响尚未得到完全阐明。
研究背景
本研究旨在探讨饮食、氟诱导氧化应激与大鼠肝脏脂质代谢之间的关联，实验对象为分别喂食正常热量或高热量饮食、并设置20天与60天两个实验周期的大鼠。
实验方法
将72只21日龄Wistar大鼠按饮食类型分为2组（每组n=36）；随后基于实验周期（20天或60天）将每组再分为2个亚组（每组n=18），最终共计4组。再根据饮用水中氟的给药剂量（0 mg/L（对照组）、15 mg/L或50 mg/L），将每个组分为3个亚组（每亚组6只动物）。实验周期结束后，采集血液样本与肝脏组织。对血浆样本进行高密度脂蛋白（HDL）、胆固醇及甘油三酯水平检测；采用蛋白质印迹（Western blots）技术检测肝脏组织中GRP78、Erp29、SOD2、Apo-E及SREBP的表达水平。
实验结果
如预期所示，氟处理组的氧化应激相关靶蛋白表达水平均升高，尤其在高热量饮食喂养大鼠的肝脏组织中更为显著。多数脂质水平与病理状态的变化在实验早期（20天）即可观察到。形态计量学分析显示，与对照组相比，高热量饮食喂养且经50 mg/L氟处理的大鼠肝脏脂肪变性程度有所降低，而正常热量饮食喂养的大鼠未出现此类变化。相应地，氟处理组大鼠的血浆甘油三酯（TG）水平有所下降。载脂蛋白E（Apo-E）的表达呈现时间与饮食依赖性降低，这或许可以解释高热量饮食喂养的氟处理大鼠肝脏脂肪变性程度特异性降低的现象。
研究结论
本研究结果表明，氟可改变肝脏脂质稳态，其潜在机制可能与氧化应激的诱导有关，且高热量饮食喂养大鼠的氧化应激水平似乎更高。