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

Biochemical Pharmacology

Volumn 71, Issue 4, 2006, Pages 453-463

  Lund, Erik G ^a   Peterson, Laurence B ^a   Adams, Alan D ^a   Lam, My Hanh N ^a   Burton, Charlotte A ^a   Chin, Jayne ^a   Guo, Qiu ^a   Huang, Shaei ^a   Latham, Melanie ^a   Lopez, Jacqueline C ^a   Menke, John G ^a   Milot, Denise P ^a   Mitnaul, Lyndon J ^a   Rex Rabe, Sandra E ^a   Rosa, Raymond L ^a   Tian, Jenny Y ^a   Wright, Samuel D ^a   Sparrow, Carl P ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

ATP binding cassette transporter A1; Cholesterol; High density lipoprotein; Macrophages; Nuclear receptor; Sterol regulatory element binding protein 1c; Triglycerides

Indexed keywords

ABC TRANSPORTER A1; CELL NUCLEUS RECEPTOR; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; LIVER X RECEPTOR ALPHA; LIVER X RECEPTOR BETA; TRIACYLGLYCEROL;

ANIMAL CELL; ARTICLE; CONTROLLED STUDY; DRUG EFFECT; DRUG POTENCY; FATTY LIVER; GENE EXPRESSION; LIPID METABOLISM; MOUSE; NONHUMAN; PERITONEUM MACROPHAGE; PRIORITY JOURNAL; TRIACYLGLYCEROL BLOOD LEVEL;

8-BROMO CYCLIC ADENOSINE MONOPHOSPHATE; ADMINISTRATION, ORAL; ANIMALS; ATP-BINDING CASSETTE TRANSPORTERS; CHOLESTEROL; CHOLESTEROL, HDL; CYCLIC AMP; DNA-BINDING PROTEINS; DOSE-RESPONSE RELATIONSHIP, DRUG; GENE EXPRESSION REGULATION; ISOXAZOLES; LIPID METABOLISM; LIVER; MACROPHAGES, PERITONEAL; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MOLECULAR STRUCTURE; PHENYLUREA COMPOUNDS; PROTEIN ISOFORMS; PYRAZINES; RECEPTORS, CYTOPLASMIC AND NUCLEAR; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; RNA, MESSENGER; STEROL REGULATORY ELEMENT BINDING PROTEIN 1; TRIGLYCERIDES;

EID: 30444447387     PISSN: 00062952     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bcp.2005.11.004     Document Type: Article

References (45)

1. E.G. Lund, J.G. Menke, and C.P. Sparrow Liver X receptor agonists as potential therapeutic agents for dyslipidemia and atherosclerosis Arterioscler Thromb Vasc Biol 23 2003 1169 1177
2. P. Tontonoz, and D.J. Mangelsdorf Liver X receptor signaling pathways in cardiovascular disease Mol Endocrinol 17 2003 985 993
3. A. Chawla, J.J. Repa, R.M. Evans, and D.J. Mangelsdorf Nuclear receptors and lipid physiology: opening the X-files Science 294 2001 1866 1870
4. X. Fu, J.G. Menke, Y. Chen, G. Zhou, K.L. MacNaul, and S.D. Wright 27-Hydroxycholesterol is an endogenous ligand for liver X receptor in cholesterol-loaded cells J Biol Chem 276 2001 38378 38387
5. D.J. Peet, S.D. Turley, W. Ma, B.A. Janowski, J.M. Lobaccaro, and R.E. Hammer Cholesterol and bile acid metabolism are impaired in mice lacking the nuclear oxysterol receptor LXR alpha Cell 93 1998 693 704
6. S. Alberti, G. Schuster, P. Parini, D. Feltkamp, U. Diczfalusy, and M. Rudling Hepatic cholesterol metabolism and resistance to dietary cholesterol in LXRbeta-deficient mice J Clin Invest 107 2001 565 573
7. J.R. Schultz, H. Tu, A. Luk, J.J. Repa, J.C. Medina, and L. Li Role of LXRs in control of lipogenesis Genes Dev 14 2000 2831 2838
8. J.L. Collins, A.M. Fivush, M.A. Watson, C.M. Galardi, M.C. Lewis, and L.B. Moore Identification of a nonsteroidal liver X receptor agonist through parallel array synthesis of tertiary amines J Med Chem 45 2002 1963 1966
9. A. Berkenstam, and J.A. Gustafsson Nuclear receptors and their relevance to diseases related to lipid metabolism Curr Opin Pharmacol 5 2005 171 176
10. J.J. Repa, and D.J. Mangelsdorf The liver X receptor gene team: potential new players in atherosclerosis Nat Med 8 2002 1243 1248
11. S.B. Joseph, M.N. Bradley, A. Castrillo, K.W. Bruhn, P.A. Mak, and L. Pei LXR-dependent gene expression is important for macrophage survival and the innate immune response Cell 119 2004 299 309
12. G. Cao, Y. Liang, X.C. Jiang, and P.I. Eacho Liver X receptors as potential therapeutic targets for multiple diseases Drug News Perspect 17 2004 35 41
13. K.R. Steffensen, and J.A. Gustafsson Putative metabolic effects of the liver X receptor (LXR) Diabetes 53 Suppl. 1 2004 S36 S42
14. B.A. Laffitte, L.C. Chao, J. Li, R. Walczak, S. Hummasti, and S.B. Joseph Activation of liver X receptor improves glucose tolerance through coordinate regulation of glucose metabolism in liver and adipose tissue Proc Natl Acad Sci USA 100 2003 5419 5424
15. K.M. Robertson, G.U. Schuster, K.R. Steffensen, O. Hovatta, S. Meaney, and K. Hultenby The liver X receptor-{beta} is essential for maintaining cholesterol homeostasis in the testis Endocrinology 146 2005 2519 2530
16. J.J. Repa, K.E. Berge, C. Pomajzl, J.A. Richardson, H. Hobbs, and D.J. Mangelsdorf Regulation of atp-binding cassette sterol transporters ABCG5 and ABCG8 by the liver X receptors alpha and beta J Biol Chem 277 2002 18793 18800
17. A.D. Attie, J.P. Kastelein, and M.R. Hayden Pivotal role of ABCA1 in reverse cholesterol transport influencing HDL levels and susceptibility to atherosclerosis J Lipid Res 42 2001 1717 1726
18. N. Terasaka, A. Hiroshima, T. Koieyama, N. Ubukata, Y. Morikawa, and D. Nakai T-0901317, a synthetic liver X receptor ligand, inhibits development of atherosclerosis in LDL receptor-deficient mice FEBS Lett 536 2003 6 11
19. S.B. Joseph, E. McKilligin, L. Pei, M.A. Watson, A.R. Collins, and B.A. Laffitte Synthetic LXR ligand inhibits the development of atherosclerosis in mice Proc Natl Acad Sci USA 99 2002 7604 7609
20. J.J. Repa, G. Liang, J. Ou, Y. Bashmakov, J.M. Lobaccaro, I. Shimomura, and B. Shan Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRalpha and LXRbeta Genes Dev 14 2000 2819 2830
21. J.D. Horton, J.L. Goldstein, and M.S. Brown SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver J Clin Invest 109 2002 1125 1131
22. S.B. Joseph, B.A. Laffitte, P.H. Patel, M.A. Watson, K.E. Matsukuma, and R. Walczak Direct and indirect mechanisms for regulation of fatty acid synthase gene expression by liver X receptors J Biol Chem 277 2002 11019 11025
23. M. Jaye LXR agonists for the treatment of atherosclerosis Curr Opin Invest Drugs 4 2003 1053 1058
24. L.J. Millatt, V. Bocher, J.C. Fruchart, and B. Staels Liver X receptors and the control of cholesterol homeostasis: potential therapeutic targets for the treatment of atherosclerosis Biochim Biophys Acta 1631 2003 107 118
25. K.R. Steffensen, M. Nilsson, G.U. Schuster, T.M. Stulnig, K. Dahlman-Wright, and J.A. Gustafsson Gene expression profiling in adipose tissue indicates different transcriptional mechanisms of liver X receptors alpha and beta, respectively Biochem Biophys Res Commun 310 2003 589 593
26. Y. Zhang, J.J. Repa, K. Gauthier, and D.J. Mangelsdorf Regulation of lipoprotein lipase by the oxysterol receptors, LXRalpha and LXRbeta J Biol Chem 276 2001 43018 43024
27. D.R. Shaw, and F.M. Griffin Jr. Thioglycollate-elicited mouse peritoneal macrophages are less efficient than resident macrophages in antibody-dependent cell-mediated cytolysis J Immunol 128 1982 433 440
28. C.P. Sparrow, J. Baffic, M.H. Lam, E.G. Lund, A.D. Adams, and X. Fu A potent synthetic LXR agonist is more effective than cholesterol loading at inducing ABCA1 mRNA and stimulating cholesterol efflux J Biol Chem 277 2002 10021 10027
29. H.R. Davis Jr., L.J. Zhu, L.M. Hoos, G. Tetzloff, M. Maguire, and J. Liu Niemann-pick c1 like 1 (npc1l1) is the intestinal phytosterol and cholesterol transporter and a key modulator of whole-body cholesterol homeostasis J Biol Chem 279 2004 33586 33592
30. E.G. Bligh, and W.J. Dyer A rapid method of total lipid extraction and purification Can J Biochem Physiol 37 1959 911 917
31. J.G. Menke, K.L. Macnaul, N.S. Hayes, J. Baffic, Y.S. Chao, and A. Elbrecht A novel liver X receptor agonist establishes species differences in the regulation of cholesterol 7alpha-hydroxylase (cyp7a) Endocrinology 143 2002 2548 2558
32. B.A. Laffitte, J.J. Repa, S.B. Joseph, D.C. Wilpitz, H.R. Kast, and D.J. Mangelsdorf LXRs control lipid-inducible expression of the apolipoprotein e gene in macrophages and adipocytes Proc Natl Acad Sci USA 98 2001 507 512
33. T. Plosch, V.W. Bloks, Y. Terasawa, S. Berdy, K. Siegler, and F. Van Der Sluijs Sitosterolemia in ABC-transporter g5-deficient mice is aggravated on activation of the liver-X receptor Gastroenterology 126 2004 290 300
34. T.P. Beyer, R.J. Schmidt, P. Foxworthy, Y. Zhang, J. Dai, and W.R. Bensch Coadministration of a liver X receptor agonist and a peroxisome proliferator activator receptor-alpha agonist in mice: effects of nuclear receptor interplay on high-density lipoprotein and triglyceride metabolism in vivo J Pharmacol Exp Ther 309 2004 861 868
35. J.K. Kim, J.J. Fillmore, Y. Chen, C. Yu, I.K. Moore, and M. Pypaert Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance Proc Natl Acad Sci USA 98 2001 7522 7527
36. N. Levin, E.D. Bischoff, C.L. Daige, D. Thomas, C.T. Vu, and R.A. Heyman Macrophage liver X receptor is required for antiatherogenic activity of LXR agonists Arterioscler Thromb Vasc Biol 25 2005 135 142
37. R.J. Aiello, D. Brees, P.A. Bourassa, L. Royer, S. Lindsey, and T. Coskran Increased atherosclerosis in hyperlipidemic mice with inactivation of ABCA1 in macrophages Arterioscler Thromb Vasc Biol 22 2002 630 637
38. J.J. Repa, S.D. Turley, J.A. Lobaccaro, J. Medina, L. Li, and K. Lustig Regulation of absorption and ABC1-mediated efflux of cholesterol by RXR heterodimers Science 289 2000 1524 1529
39. R. Walczak, S.B. Joseph, B.A. Laffitte, A. Castrillo, L. Pei, and P. Tontonoz Transcription of the vascular endothelial growth factor gene in macrophages is regulated by liver X receptors J Biol Chem 279 2004 9905 9911
40. X.C. Jiang, T.P. Beyer, Z. Li, J. Liu, W. Quan, and R.J. Schmidt Enlargement of high density lipoprotein in mice via liver X receptor activation requires apolipoprotein e and is abolished by cholesteryl ester transfer protein expression J Biol Chem 278 2003 49072 49078
41. J.D. Smith, M. Miyata, M. Ginsberg, C. Grigaux, E. Shmookler, and A.S. Plump Cyclic amp induces apolipoprotein e binding activity and promotes cholesterol efflux from a macrophage cell line to apolipoprotein acceptors J Biol Chem 271 1996 30647 30655
42. Y. Takahashi, M. Miyata, P. Zheng, T. Imazato, A. Horwitz, and J.D. Smith Identification of camp analogue inducible genes in raw264 macrophages Biochim Biophys Acta 1492 2000 385 394
43. S. Abe-Dohmae, S. Suzuki, Y. Wada, H. Aburatani, D.E. Vance, and S. Yokoyama Characterization of apolipoprotein-mediated HDL generation induced by camp in a murine macrophage cell line Biochemistry 39 2000 11092 11099
44. K. Schwartz, R.M. Lawn, and D.P. Wade ABC1 gene expression and apoA-I-mediated cholesterol efflux are regulated by LXR Biochem Biophys Res Commun 274 2000 794 802
45. J. Chin, A.D. Adams, A. Bouffard, A. Green, R.G. Lacson, T. Smith, and P.A. Fischer Miniaturization of cell-based beta-lactamase-dependent fret assays to ultra-high throughput formats to identify agonists of human liver X receptors Assay Drug Dev Technol 1 2003 777 787