Mice in the early stage of liver steatosis caused by a high fat diet are resistant to thioacetamide-induced hepatotoxicity and oxidative stress
Mice in the early stage of liver steatosis caused by a high fat diet are resistant to thioacetamide-induced hepatotoxicity and oxidative stress
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DOI：
10.1016/j.toxlet.2017.06.005
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发表时间：
2017-08-01
影响因子：
3.5
通讯作者：
Fujii, Junichi
中科院分区：
文献类型：
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作者：
Lee, Jaeyong;Homma, Takujiro;Fujii, Junichi
在多种病理条件下，通过对内质网应激的未折叠蛋白反应（UPR）刺激肝脏中的脂肪生成，并导致脂质在肝细胞中积累。假设UPR是一种对抗压力的保护机制，我们假设积累的脂质可能具有有益的功能。我们通过喂养两种类型的高热量饮食来制备脂肪肝小鼠;富含猪油的高热量饮食（LHD）或含鲱鱼油的高热量饮食（MHD），持续两周，并用硫代乙酰胺（TAA）治疗它们，以及对照饮食（CD）喂养的小鼠。当给予致死剂量（500 mg/kg）的TAA时，LHD喂养的小鼠和MHD喂养的小鼠比CD喂养的小鼠存活时间更长。蓄积的脂质似乎与保护肝脏免受TAA毒性（200 mg/kg）有关。一致的是，脂质负载的Hepa 1-6细胞显示出对过氧化氢毒性的部分抗性，与在常规培养基中培养的细胞相比。总之，虽然持续的脂肪变性损害肝功能并导致危险状况，但由于UPR或其他刺激而暂时积累的脂质可能至少部分通过清除活性氧在肝脏中发挥有益功能。
Lipogenesis is stimulated in the liver by an unfolded protein response (UPR) to endoplasmic reticulum stress under a variety of pathological conditions and results in the accumulation of lipids in hepatocytes. Assuming that UPR is a protective mechanism against stress, we hypothesized that the accumulated lipids might have a beneficial function. We prepared mice with fatty livers by feeding two types of high-calorie diets; a lard-rich highcalorie diet (LHD) or a menhaden oil-containing high-calorie diet (MHD), for two weeks and treated them, as well as control diet (CD)-fed mice, with thioacetamide (TAA), a liver toxicant. When a lethal dose (500 mg/kg) of TAA was administered, the LHD-fed mice and the MHD-fed mice survived longer than those fed with CD. The accumulated lipids appeared to be associated with protecting the liver against TAA toxicity (200 mg/kg). Consistently, lipid-loaded Hepa 1-6 cells showed a partial resistance to hydrogen peroxide toxicity compared to those cultured in conventional media. In conclusion, while sustained steatosis impairs liver function and leads to hazardous conditions, lipids that transiently accumulate as the result of UPR or other stimuli may exert a beneficial function in the liver at least partly through scavenging reactive oxygen species.