Deletion of Perilipin 5 Protects against Hepatic Injury in Nonalcoholic Fatty Liver Disease via Missing Inflammasome Activation
Deletion of Perilipin 5 Protects against Hepatic Injury in Nonalcoholic Fatty Liver Disease via Missing Inflammasome Activation
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DOI：
10.3390/cells9061346
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发表时间：
2020-06-01
期刊：
影响因子：
6
通讯作者：
Weiskirchen, Ralf
中科院分区：
文献类型：
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作者：
Asimakopoulou, Anastasia;Engel, Kathrin M.;Weiskirchen, Ralf
非酒精性脂肪性肝病（NAFLD）是慢性肝病的主要原因，由于肥胖、代谢综合征和II型糖尿病的发病率上升，其患病率不断增加。未经治疗的NAFLD可能进展为脂肪性肝炎（NASH）并最终发展为肝硬化。NAFLD的特征是脂质蓄积，当获得足够的过量脂质时，可能会发生不可逆的肝损伤。周脂蛋白5（PLIN 5）是一种已知的脂滴包被蛋白和甘油三酯代谢调节剂，在氧化修饰的组织中高度表达，但仍不清楚它如何影响NAFLD/NASH进展。我们在此研究了PLIN 5如何影响野生型和PLIN 5敲除（Plin 5（-/-））小鼠中由30周高脂饮食（HFD）施用诱导的NAFLD发展。PLIN 5的破坏诱导了HFD喂养期间脂质代谢的差异，并与肝脏脂肪蓄积减少相关。令人惊讶的是，Plin 5（-/-）小鼠显示出NLR家族含pyrin结构域3（NLRP 3）炎性体的活化减轻，导致轻微的肝损伤。我们得出结论，PLIN 5是NASH发展中肝脏稳态的多效性调节剂。靶向PLIN 5表达对于保护肝脏免受慢性NAFLD期间的炎症激活至关重要。
Nonalcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver diseases with an increasing prevalence due to rising rates of obesity, metabolic syndrome and type II diabetes. Untreated NAFLD may progress to steatohepatitis (NASH) and ultimately liver cirrhosis. NAFLD is characterized by lipid accumulation, and when sufficient excess lipids are obtained, irreversible liver injury may follow. Perilipin 5 (PLIN5), a known lipid droplet coating protein and triglyceride metabolism regulator, is highly expressed in oxidatively modified tissues but it is still unclear how it affects NAFLD/NASH progress. We here studied how PLIN5 affects NAFLD development induced by a 30-week high-fat diet (HFD) administration in wild type and PLIN5 knock out (Plin5(-/-)) mice. The disruption of PLIN5 induced differences in lipid metabolism during HFD feeding and was associated with reduced hepatic fat accumulation. Surprisingly,Plin5(-/-)mice showed mitigated activation of the NLR family pyrin domain-containing 3 (NLRP3) inflammasome, leading to minor hepatic damage. We conclude that PLIN5 is a pleiotropic regulator of hepatic homeostasis in NASH development. Targeting the PLIN5 expression appears critical for protecting the liver from inflammatory activation during chronic NAFLD.