Molecular biology and functional genomics of liver X receptors (LXR) in relationship to metabolic diseases

被引:50
作者
Faulds, Malin Hedengran [1 ]
Zhao, Chunyan [1 ]
Dahlman-Wright, Karin [1 ]
机构
[1] Karolinska Inst, Dept Biosci & Nutr, S-14183 Huddinge, Sweden
关键词
ELEMENT-BINDING PROTEIN-1C; BILE-ACID BIOSYNTHESIS; CHOLESTEROL-METABOLISM; OXYSTEROL RECEPTORS; LIPOPROTEIN-LIPASE; LIPID-METABOLISM; GENE-EXPRESSION; MICE LACKING; PPAR-GAMMA; IN-VIVO;
D O I
10.1016/j.coph.2010.07.003
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The metabolic syndrome constitutes a group of metabolic conditions that increase the risk of developing diseases, including cardiovascular disease (CVD) and type 2 diabetes (120) LXR alpha/beta are regulators of lipogenesis, cholesterol/glucose homoeostasis and inflammatory pathways, processes that are intertwined with development of the metabolic syndrome The employment of LXRs as pharmaceutical targets for treatment of various aspects of the metabolic syndrome has been promptly investigated but serious side effects like hepatic steatosis have hampered this process Novel treatment regimes now focus on development of isoform-specific or tissue-specific LXR agonist/antagonist compounds to circumvent effects on lipid biosynthesis Other strategies to explore the beneficial aspects of LXR activation include targeting co-factors or pathways that are modifying LXR activity
引用
收藏
页码:692 / 697
页数:6
相关论文
共 41 条
[21]   Direct and indirect mechanisms for regulation of fatty acid synthase gene expression by liver X receptors [J].
Joseph, SB ;
Laffitte, BA ;
Patel, PH ;
Watson, MA ;
Matsukuma, KE ;
Walczak, R ;
Collins, JL ;
Osborne, TF ;
Tontonoz, P .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (13) :11019-11025
[22]   Synthetic LXR ligand inhibits the development of atherosclerosis in mice [J].
Joseph, SB ;
McKilligin, E ;
Pei, LM ;
Watson, MA ;
Collins, AR ;
Laffitte, BA ;
Chen, MY ;
Noh, G ;
Goodman, J ;
Hagger, GN ;
Tran, J ;
Tippin, TK ;
Wang, XP ;
Lusis, AJ ;
Hsueh, WA ;
Law, RE ;
Collins, JL ;
Willson, TM ;
Tontonoz, P .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (11) :7604-7609
[23]   Characterization of ASC-2 as an Antiatherogenic Transcriptional Coactivator of Liver X Receptors in Macrophages [J].
Kim, Geun Hyang ;
Park, Keunhee ;
Yeom, Seon-Yong ;
Lee, Kyung Jin ;
Kim, Gukhan ;
Ko, Jesang ;
Rhee, Dong-Kwon ;
Kim, Young Hoon ;
Lee, Hye Kyung ;
Kim, Hae Won ;
Oh, Goo Taeg ;
Lee, Ki-Up ;
Lee, Jae W. ;
Kim, Seung-Whan .
MOLECULAR ENDOCRINOLOGY, 2009, 23 (07) :966-974
[24]   Liver X receptor modulators: a review of recently patented compounds (2007-2009) [J].
Li, Xiaolin ;
Yeh, Vince ;
Molteni, Valentina .
EXPERT OPINION ON THERAPEUTIC PATENTS, 2010, 20 (04) :535-562
[25]   Diminished hepatic response to fasting/refeeding and liver X receptor agonists in mice with selective deficiency of sterol regulatory element-binding protein-1c [J].
Liang, GS ;
Yang, J ;
Horton, JD ;
Hammer, RE ;
Goldstein, JL ;
Brown, MS .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (11) :9520-9528
[26]   Hyperlipidemic effects of dietary saturated fats mediated through PGC-1β cactivation of SREBP [J].
Lin, JD ;
Yang, RJ ;
Tarr, PT ;
Wu, PH ;
Handschin, C ;
Li, SM ;
Yang, WL ;
Pei, LM ;
Uldry, M ;
Tontonoz, P ;
Newgard, CB ;
Spiegelman, BM .
CELL, 2005, 120 (02) :261-273
[27]   Different roles of liver X receptor α and β in lipid metabolism:: Effects of an α-selective and a dual agonist in mice deficient in each subtype [J].
Lund, EG ;
Peterson, LB ;
Adams, AD ;
Lam, MHN ;
Burton, CA ;
Chin, J ;
Guo, Q ;
Huang, S ;
Latham, M ;
Lopez, JC ;
Menke, JG ;
Milot, DP ;
Mitnaul, LJ ;
Rex-Rabe, SE ;
Rosa, RL ;
Tian, JY ;
Wright, SD ;
Sparrow, CP .
BIOCHEMICAL PHARMACOLOGY, 2006, 71 (04) :453-463
[28]   Sterol upregulation of human CETP expression in vitro and in transgenic mice by an LXR element [J].
Luo, Y ;
Tall, AR .
JOURNAL OF CLINICAL INVESTIGATION, 2000, 105 (04) :513-520
[29]   Liver X Receptor Agonists Augment Human Islet Function through Activation of Anaplerotic Pathways and Glycerolipid/Free Fatty Acid Cycling [J].
Ogihara, Takeshi ;
Chuang, Jen-Chieh ;
Vestermark, George L. ;
Garmey, James C. ;
Ketchum, Robert J. ;
Huang, Xiaolun ;
Brayman, Kenneth L. ;
Thorner, Michael O. ;
Repa, Joyce J. ;
Mirmira, Raghavendra G. ;
Evans-Molina, Carmella .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (08) :5392-5404
[30]   Cholesterol and bile acid metabolism are impaired in mice lacking the nuclear oxysterol receptor LXRα [J].
Peet, DJ ;
Turley, SD ;
Ma, WZ ;
Janowski, BA ;
Lobaccaro, JMA ;
Hammer, RE ;
Mangelsdorf, DJ .
CELL, 1998, 93 (05) :693-704