Vicente C P, Guaragna R M, Borojevic R
Departamento de Bioquímica, Universidade Federal do Rio de Janeiro, Brasil.
Mol Cell Biochem. 1997 Mar;168(1-2):31-9. doi: 10.1023/a:1006845808305.
Molecular mechanisms of lipid synthesis and their controls in hepatic stellate cells are not known. We have previously proposed that, in contrast to other fat storing cells, hepatic stellate cells are not involved in energy storage, but they represent a particular cell population specialized in storage of lipid-soluble substances, the major one being probably retinol. In agreement with this hypothesis, induction of the lipocyte phenotype in stellate cells is not under the control of insulin, but responds to retinoids and other molecules that modify the gene expression program in these cells. In the present study we have monitored the activity of the two major enzymes involved in lipid synthesis during the induction of the lipocyte phenotype in hepatic stellate cells: glycerol-3-phosphate dehydrogenase (GPDH) that mediates the de novo lipid synthesis, and lipoprotein lipase that mediates incorporation of plasma lipids. In early stages of lipocyte induction, both pathways of lipid synthesis are activated. When lipocytes have already constituted the lipid droplets, lipoprotein lipase pathway is downregulated, while GPDH activity remains high. Adult liver has been reported to lack lipoprotein lipase, but under stress, lipase activity was detected around and at the surface of the intrahepatic vasculature. We have now shown that the lipase activity can be induced in the hepatic stellate cells, located in the Disse's space. The high lipoprotein lipase activity under acute induction of lipocyte phenotype, followed by the low activity under conditions of metabolic equilibrium, are in compass with the increased activity of this enzyme under stress, and its low activity in adult liver parenchyma under normal conditions.
肝星状细胞中脂质合成的分子机制及其调控尚不清楚。我们之前曾提出，与其他脂肪储存细胞不同，肝星状细胞不参与能量储存，而是代表一种特殊的细胞群体，专门储存脂溶性物质，其中主要的可能是视黄醇。与这一假设一致，星状细胞中脂肪细胞表型的诱导不受胰岛素控制，而是对类视黄醇和其他能改变这些细胞基因表达程序的分子有反应。在本研究中，我们监测了肝星状细胞脂肪细胞表型诱导过程中参与脂质合成的两种主要酶的活性：介导从头脂质合成的甘油-3-磷酸脱氢酶（GPDH）和介导血浆脂质掺入的脂蛋白脂肪酶。在脂肪细胞诱导的早期阶段，脂质合成的两条途径均被激活。当脂肪细胞已经形成脂滴时，脂蛋白脂肪酶途径下调，而GPDH活性仍然很高。据报道，成年肝脏缺乏脂蛋白脂肪酶，但在应激状态下，在肝内血管周围和表面检测到脂肪酶活性。我们现在已经表明，位于狄氏间隙的肝星状细胞中可以诱导脂肪酶活性。脂肪细胞表型急性诱导下的高脂蛋白脂肪酶活性，随后在代谢平衡条件下的低活性，与该酶在应激状态下的活性增加以及在正常条件下成年肝实质中的低活性相一致。
