期刊
JOURNAL OF LIPID RESEARCH
卷 45, 期 8, 页码 1410-1417出版社
ELSEVIER
DOI: 10.1194/jlr.M300450-JLR200
关键词
high density lipoprotein; liver X receptor; fatty acid synthetase; sterol response element binding protein 1-c; triglyceride
Liver X receptors (LXRs) are ligand-activated transcription factors that belong to the nuclear receptor superfamily. LXRs activate transcription of a spectrum of genes that regulate reverse cholesterol transport, including the ATP binding cassette transporter A1 (ABCA1), and raise HDL cholesterol (HDL-C) levels. However, LXR agonists also induce genes that stimulate lipogenesis, including the sterol response element binding protein (SREBP1-c) and fatty acid synthetase (FAS). The induction of these genes in the liver cause increased hepatic triglyceride synthesis, hypertriglyceridemia, and hepatic steatosis. As LXR response elements have been identified in these promoters, it is not clear if these two processes can be separated. Herein, we demonstrate that plasma HDLC elevation and intestinal ABCA1 induction can occur with relatively little induction of FAS and SREBP1-c in mouse liver via a selective LXR modulator GW3965. This is in contrast to the strong induction of hepatic lipogenic genes by the well-characterized LXR agonist T0901317 (T317). Consistent with the in vivo results, GW3965 is a very weak LXR activator compared with T317 in human hepatoma cells. GW3965-liganded LXR recruits selected coactivators less effectively than T317 and may explain in part the tissue selective gene induction.j r This demonstration that tissue and gene selective modulation is possible with selective LXR modulators has positive implications for the development of this class of antiatherosclerotic agents.-Miao, B., S. Zondlo, S. Gibbs, D. Cromley, V. P. Hosagrahara, T. G. Kirchgessner, J. Billheimer, and R. Mukherjee. Raising HDL cholesterol without inducing hepatic steatosis and hypertriglyceridemia by a selective LXR modidator.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据