Activation of cholesterol synthesis in preference to fatty acid synthesis in liver and adipose tissue of transgenic mice overproducing sterol regulatory element-binding protein-2.

摘要: We produced transgenic mice that express a dominant-posi- tive truncated form of sterol regulatory element-binding protein-2 (SREBP-2) in liver and adipose tissue. The en- coded protein lacks the membrane-binding COOH-ter- minal domains, it is therefore not susceptible to negative regulation by cholesterol. Livers from trans- genic showed increases mRNAs encoding multi- ple enzymes cholesterol biosynthesis, LDL recep- tor, fatty acid biosynthesis. elevations mRNA for 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) synthase HMG CoA reductase were especially marked (13-fold 75-fold, respectively). As result, livers 28-fold increase rate choles- terol synthesis lesser fourfold synthesis, as measured intraperitoneal injection ( 3 H)water. These results contrast with previously reported effects dominant-positive SREBP-1a, which activated more than synthesis. In adi- pose tissue SREBP-2 transgenics, biosynthetic elevated, but not. conclude relatively selective activator opposed mice. J. Clin. Invest. 1998. 101: 2331-2339.) Key words: cholesterollow density lipoprotein • element binding proteinsfatty acids