Akebia Saponin D Decreases Hepatic Steatosis through Autophagy Modulation
Akebia Saponin D Decreases Hepatic Steatosis through Autophagy Modulation
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DOI：
10.1124/jpet.116.236562
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发表时间：
2016-12-01
影响因子：
3.5
通讯作者：
Liu, Li-hong
中科院分区：
文献类型：
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作者：
Gong, Li-li;Li, Guang-run;Liu, Li-hong
非酒精性脂肪性肝病（NAFLD）被认为是代谢综合征的一种肝脏表现，其发病率正在迅速增加。然而，缺乏治疗NAFLD的合适药物。本研究旨在探讨木通皂苷D（ASD）对ob/ob小鼠和布法罗大鼠肝细胞NAFLD的保护作用及其机制。ASD可显着减少ob/ob小鼠的肝脏脂肪变性和肝细胞凋亡。ASD还显著激活自噬通量，如通过自噬体的轻链3（LC 3）-II和P62积累的表达降低所评估的。在布法罗大鼠肝细胞中，ASD阻止油酸（OA）诱导的脂滴，并增加自噬通量，因为自溶酶体的数量比mTagRFP-mWasabi-LC 3中的自噬体增加。ASD治疗还阻止了OA诱导的LC 3-II、P62、Beclin和磷酸化哺乳动物雷帕霉素靶标的表达。这些效果与雷帕霉素的共处理相似。ASD治疗不能阻止用氯喹或小干扰RNA介导的atg 7敲低治疗后OA增加的自噬相关蛋白表达。这些结果表明，ASD以自噬体与溶酶体融合为靶点，促进肝脂肪变性，通过ASD调节自噬可能为治疗NAFLD提供新的策略。
Nonalcoholic fatty liver disease (NAFLD) is considered to be a hepatic manifestation of the metabolic syndrome, and the incidence of NAFLD is increasing rapidly. However, appropriate drugs for treatment of NAFLD are lacking. This study aimed to elucidate the protective effects and mechanisms of Akebia saponin D (ASD) against NAFLD in ob/ob mice and Buffalo rat liver cells. ASD significantly decreased hepatic steatosis and hepatocyte apoptosis in ob/ob mice. ASD also significantly activated autophagic flux, as assessed by the decreased expression of light chain 3 (LC3)-II and P62 accumulation of autophagosomes. In Buffalo rat liver cells, ASD prevented oleic acid (OA)-induced lipid droplets and increased autophagic flux acting as increase the number of autolysosomes than autophagosomes in mTagRFP-mWasabi-LC3. ASD treatment also prevented OA-induced expression of LC3-II, P62, Beclin, and phospho-mammalian target of rapamycin. These effects were similar to those of cotreatment with rapamycin. ASD treatment could not prevent OA-increased, autophagy-related protein expression after treatment with chloroquine or small interfering RNA-mediated knockdown of atg7. These results suggest that ASD alleviates hepatic steatosis targeted at the fusion of autophagosomes to lysosomes, and autophagy modulation via ASD may offer a new strategy for treating NAFLD.