Further experimentation revealed that the increase in LXRa differentially regulated the expression of other important metabolic genes.
"Liver X receptors had emerged as key regulators of cholesterol and lipid metabolism," said Lazar. "The current study elucidates a previously unrecognized role for these liver receptors in the links between diet, serum lipids, and atherosclerosis."
Selective modulation of the LXR target genes in liver may therefore ameliorate high lipid levels and cardiovascular disease, the researchers said.
The researchers include Michael Lehrke, Corinna Lebherz, Segan Millington, Hong-Ping Guan, John Millar, Daniel J. Rader, James M. Wilson, and Mitchell A. Lazar of the University of Pennsylvania School of Medicine. This work was supported by NIH grants, the Penn Diabetes and Endocrinology Research Center, and a Bristol Myers Squibb Freedom to Discover Award in Metabolic Research. M.L. was supported by a Deutsche Forschungsgemeinschaft fellowship.
Lehrke, M., Lebherz, C, Millington, S., Guan, H.-P., Millar, J., Rader, D.J., Wilson, J.M., and Lazar, M.A. (2005). Diet-dependent cardiovascular lipid metabolism controlled by hepatic LXRalpha. Cell Metab. 1, 297-308.