Listenberger Laura, Townsend Elizabeth, Rickertsen Cassandra, Hains Anastasia, Brown Elizabeth, Inwards Emily G, Stoeckman Angela K, Matis Mitchell P, Sampathkumar Rebecca S, Osna Natalia A, Kharbanda Kusum K
Departments of Biology and Chemistry, St. Olaf College, Northfield, MN 55057, USA.
Department of Chemistry, Bethel University, St. Paul, MN 55112, USA.
Cells. 2018 Nov 24;7(12):230. doi: 10.3390/cells7120230.
Alcoholic fatty liver disease (AFLD) is characterized by an abnormal accumulation of lipid droplets (LDs) in the liver. Here, we explore the composition of hepatic LDs in a rat model of AFLD. Five to seven weeks of alcohol consumption led to significant increases in hepatic triglyceride mass, along with increases in LD number and size. Additionally, hepatic LDs from rats with early alcoholic liver injury show a decreased ratio of surface phosphatidylcholine (PC) to phosphatidylethanolamine (PE). This occurred in parallel with an increase in the LD association of perilipin 2, a prominent LD protein. To determine if changes to the LD phospholipid composition contributed to differences in protein association with LDs, we constructed liposomes that modeled the LD PC:PE ratios in AFLD and control rats. Reducing the ratio of PC to PE increased the binding of perilipin 2 to liposomes in an in vitro experiment. Moreover, we decreased the ratio of LD PC:PE in NIH 3T3 and AML12 cells by culturing these cells in choline-deficient media. We again detected increased association of specific LD proteins, including perilipin 2. Taken together, our experiments suggest an important link between LD phospholipids, protein composition, and lipid accumulation.
酒精性脂肪性肝病（AFLD）的特征是肝脏中脂质小滴（LDs）异常蓄积。在此，我们在AFLD大鼠模型中探究肝脏LDs的组成。五到七周的酒精摄入导致肝脏甘油三酯含量显著增加，同时LDs数量和大小也增加。此外，早期酒精性肝损伤大鼠的肝脏LDs显示表面磷脂酰胆碱（PC）与磷脂酰乙醇胺（PE）的比例降低。这与主要的LD蛋白脂滴包被蛋白2（perilipin 2）与LDs的结合增加同时发生。为了确定LD磷脂组成的变化是否导致与LDs结合的蛋白质存在差异，我们构建了模拟AFLD大鼠和对照大鼠LD PC:PE比例的脂质体。在体外实验中，降低PC与PE的比例增加了perilipin 2与脂质体的结合。此外，我们通过在胆碱缺乏的培养基中培养NIH 3T3和AML12细胞，降低了细胞中LD PC:PE的比例。我们再次检测到包括perilipin 2在内的特定LD蛋白的结合增加。综上所述，我们的实验表明LD磷脂、蛋白质组成和脂质蓄积之间存在重要联系。
