The focus of the Liang laboratory is to study the molecular mechanism by which dysregulation of lipid metabolism contributes to the development of diseases such as obesity, diabetes, and birth defects. Currently, we are using genetically modified rodent models to elucidate the physiological roles of SREBP, Scap, and Insig. To achieve this goal, we have generated

various mutant mouse lines that either lack or overexpress these key regulators of lipid metabolism in specific tissues such as brain, liver, and muscle.

RECENT PUBLICATIONS

Yang, J., Brown, M.S., Liang, G., Grishin, N.V., and Goldstein, J.L. Identification of the Acyltransferase that Octanoylates Ghrelin, an Appetite-Stimulating Peptide Hormone. Cell 132:387-396 (2008).

Engelking, L.J., Evers, B.M., Richardson, J.A., Goldstein, J.L., Brown, M.S., and Liang G. Severe facial clefting in Insig-deficient mouse embryos caused by sterol accumulation and reversed by lovastatin. J. Clin. Invest. 116:2356-2365 (2006).

Engelking, L.J., Liang, G., Hammer, R.E., Takaishi, K., Kuriyama, H., Evers, B.M., Li, W.-P., Horton, J.D., Goldstein, J.L., and Brown, M.S. Schoenheimer effect explained: feedback regulation of cholesterol synthesis in mice requires Insig-1 and Insig-2. J. Clin. Invest. 115: 2489-2498 (2005).

Kuriyama, H., Liang, G., Engelking, L.J., Horton, J.D., Goldstein, J.L., and Brown, M.S. Compensatory increase in fatty acid synthesis in adipose tissue of mice with conditional deficiency of SCAP in liver. Cell Metabolism. 1: 41-51 (2005).

Chen G., Liang, G., Ou, J., Goldstein J.L., and Brown, M.S. Central role for liver X receptor in insulin-mediated activation of Srebp-1c transcription and stimulation of fatty acid synthesis in liver. Proc. Natl. Acad. Sci. USA. 101: 11245-11250 (2004).

Engelking, L. J., Kuriyama, H., Hammer, R.E., Horton, J.D., Brown, M.S., Goldstein J.L., and Liang, G. Overexpression of Insig-1 in livers of transgenic mice inhibits SREBP processing and reduces insulin-stimulated lipogenesis. J. Clin. Invest. 113: 1168-1175 (2004).

Lizuka, K., Bruick, R.K., Liang, G., Horton, J.D., and Uyeda, K. Deficiency of carbohydrate response element binding protein reduces lipogenesis as well as glycolysis. Proc. Natl. Acad. Sci. USA. 101:7281-7286 (2004).

Yabe, D., Komuro, R., Liang G., Goldstein J.L., and Brown, M.S. Liver-specific mRNA for Insig-2 down-regulated by insulin: Implications for fatty acid synthesis. Proc. Natl. Acad. Sci. USA 100: 3155-3160 (2003).

Liang, G., Yang, J., Horton, J.D., Hammer, R.E., Goldstein J.L., and Brown, M.S. Diminished hepatic response to fasting/refeeding and LXR agonists in mice with selective deficiency of SREBP-1c. J. Biol. Chem. 277: 9520-9528 (2002).

Repa, J.J.*, Liang, G.*, Ou, J., Bashmakov, Y., Lobaccaro, J.A., Shimomura, I., Shan, B., Brown, M.S., Goldstein, J.L., and Mangelsdorf, D.J. Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRalpha and LXRbeta. Genes Dev. 14: 2819-2830 (2000). (*Co-first authors).