Role of LXRs in control of lipogenesis

Genes and Development - Tập 14 Số 22 - Trang 2831-2838 - 2000
Joshua R. Schultz1, Hua Tu1, Alvin Luk1, Joyce J. Repa2, Julio C. Medina1, Leping Li, Susan W. Schwendner1, Shelley Wang1, Martin Thoolen1, David J. Mangelsdorf2,1, Kevin D. Lustig1, Bei Shan1
1Tularik, Inc., South San Francisco, California 94080, USA
2Howard Hughes Medical Institute and Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA

Tóm tắt

The discovery of oxysterols as the endogenous liver X receptor (LXR) ligands and subsequent gene targeting studies in mice provided strong evidence that LXR plays a central role in cholesterol metabolism. The identification here of a synthetic, nonsteroidal LXR-selective agonist series represented by T0314407 and T0901317 revealed a novel physiological role of LXR. Oral administration of T0901317 to mice and hamsters showed that LXR activated the coordinate expression of major fatty acid biosynthetic genes (lipogenesis) and increased plasma triglyceride and phospholipid levels in both species. Complementary studies in cell culture and animals suggested that the increase in plasma lipids occurs via LXR-mediated induction of the sterol regulatory element-binding protein 1 (SREBP-1) lipogenic program.

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Tài liệu tham khảo

10.1161/01.CIR.101.24.2777

10.1056/NEJM199609193351203

10.1074/jbc.270.43.25578

Brewer, 1999, Hypertriglyceridemia: Changes in the plasma lipoproteins associated with an increased risk of cardiovascular disease., Am. J. Cardiol., 83, 3F, 10.1016/S0002-9149(99)00308-2

10.1016/S0092-8674(00)80213-5

Bucolo, 1973, Quantitative determination of serum triglycerides by the use of enzymes., Clin. Chem., 19, 476, 10.1093/clinchem/19.5.476

Chait, 1990, Acquired hyperlipidemia (secondary dyslipoproteinemias)., Endocrinol. Metab. Clin. N. Am., 19, 259, 10.1016/S0889-8529(18)30324-4

10.1074/jbc.M003337200

10.1074/jbc.272.11.7298

Ghiselli, 1982, Familial apolipoprotein E deficiency., J. Clin. Investig., 70, 474, 10.1172/JCI110638

10.1038/42750

Hodis, 1999, Pathophysiology of triglyceride-rich lipoproteins in atherothrombosis: Clinical aspects., Clin. Cardiol., 22, 15, 10.1002/clc.4960221404

10.1097/00043798-199604000-00014

10.1097/00041433-199904000-00008

10.1172/JCI2961

10.1126/science.2167514

10.1073/pnas.96.1.266

10.1038/383728a0

10.1210/me.14.1.27

10.1074/jbc.272.6.3137

10.1073/pnas.93.3.1049

10.1172/JCI8573

Parrott, 1992, ApoC-IIParis2: A premature termination mutation in the signal peptide of apoC-II resulting in the familial chylomicronemia syndrome., J. Lipid Res., 33, 361, 10.1016/S0022-2275(20)41526-3

10.1016/S0092-8674(00)81432-4

10.1101/gad.844900

10.1126/science.289.5484.1524

10.1056/NEJM199908053410604

10.1073/pnas.92.4.935

10.1172/JCI118951

10.1074/jbc.273.52.35299

10.1073/pnas.91.23.10809

Sullivan, 1998, Marked hypertriglyceridaemia associated with ritonavir therapy., AIDS, 12, 1393, 10.1097/00002030-199811000-00024

10.1074/jbc.275.19.14700

10.1101/gad.9.9.1033

10.1126/science.2244210

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Genes and Development

Tập 14 Số 22

2831-2838

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