JAY HORTON

Summary

Affiliation: University of Texas Southwestern Medical Center
Country: USA

Publications

  1. pmc Combined analysis of oligonucleotide microarray data from transgenic and knockout mice identifies direct SREBP target genes
    Jay D Horton
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390 9046, USA
    Proc Natl Acad Sci U S A 100:12027-32. 2003
  2. doi request reprint Blocking VLDL secretion causes hepatic steatosis but does not affect peripheral lipid stores or insulin sensitivity in mice
    Kaori Minehira
    Gladstone Institute of Cardiovascular Disease, University of California San Francisco, CA 94158, USA
    J Lipid Res 49:2038-44. 2008
  3. pmc WholePathwayScope: a comprehensive pathway-based analysis tool for high-throughput data
    Ming Yi
    Advanced Biomedical Computing Center, National Cancer Institute Frederick SAIC Frederick Inc, Frederick, MD 21702, USA
    BMC Bioinformatics 7:30. 2006
  4. ncbi request reprint Overexpression of sterol regulatory element-binding protein-1a in mouse adipose tissue produces adipocyte hypertrophy, increased fatty acid secretion, and fatty liver
    Jay D Horton
    Departments of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9046, USA
    J Biol Chem 278:36652-60. 2003
  5. pmc Molecular biology of PCSK9: its role in LDL metabolism
    Jay D Horton
    Departments of Internal Medicine and Molecular Genetics, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390 9046, USA
    Trends Biochem Sci 32:71-7. 2007
  6. ncbi request reprint Sterol regulatory element-binding proteins: transcriptional activators of lipid synthesis
    J D Horton
    Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75390 9046, USA
    Biochem Soc Trans 30:1091-5. 2002
  7. pmc Physiology. Unfolding lipid metabolism
    Jay D Horton
    Department of Molecular Genetics, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390 9046, USA
    Science 320:1433-4. 2008
  8. pmc SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver
    Jay D Horton
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9046, USA
    J Clin Invest 109:1125-31. 2002
  9. pmc PCSK9: a convertase that coordinates LDL catabolism
    Jay D Horton
    Department of Internal Medicine, The Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390 9046, USA
    J Lipid Res 50:S172-7. 2009
  10. ncbi request reprint Compensatory increase in fatty acid synthesis in adipose tissue of mice with conditional deficiency of SCAP in liver
    Hiroshi Kuriyama
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    Cell Metab 1:41-51. 2005

Research Grants

Collaborators

Detail Information

Publications39

  1. pmc Combined analysis of oligonucleotide microarray data from transgenic and knockout mice identifies direct SREBP target genes
    Jay D Horton
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390 9046, USA
    Proc Natl Acad Sci U S A 100:12027-32. 2003
    ....
  2. doi request reprint Blocking VLDL secretion causes hepatic steatosis but does not affect peripheral lipid stores or insulin sensitivity in mice
    Kaori Minehira
    Gladstone Institute of Cardiovascular Disease, University of California San Francisco, CA 94158, USA
    J Lipid Res 49:2038-44. 2008
    ..Thus, blocking VLDL secretion causes hepatic steatosis without insulin resistance, and there is little effect on muscle triglyceride stores or adiposity...
  3. pmc WholePathwayScope: a comprehensive pathway-based analysis tool for high-throughput data
    Ming Yi
    Advanced Biomedical Computing Center, National Cancer Institute Frederick SAIC Frederick Inc, Frederick, MD 21702, USA
    BMC Bioinformatics 7:30. 2006
    ..We have developed a comprehensive software tool, WholePathwayScope (WPS), for deriving biological insights from analysis of HTP data...
  4. ncbi request reprint Overexpression of sterol regulatory element-binding protein-1a in mouse adipose tissue produces adipocyte hypertrophy, increased fatty acid secretion, and fatty liver
    Jay D Horton
    Departments of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9046, USA
    J Biol Chem 278:36652-60. 2003
    ..These results suggest that nSREBP-1a and nSREBP-1c have distinct roles in adipocyte fat metabolism in vivo...
  5. pmc Molecular biology of PCSK9: its role in LDL metabolism
    Jay D Horton
    Departments of Internal Medicine and Molecular Genetics, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390 9046, USA
    Trends Biochem Sci 32:71-7. 2007
    ..Although the mechanism of PCSK9 action is not yet clear, the protease provides a new therapeutic target to lower plasma levels of LDL and prevent CHD...
  6. ncbi request reprint Sterol regulatory element-binding proteins: transcriptional activators of lipid synthesis
    J D Horton
    Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75390 9046, USA
    Biochem Soc Trans 30:1091-5. 2002
    ....
  7. pmc Physiology. Unfolding lipid metabolism
    Jay D Horton
    Department of Molecular Genetics, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390 9046, USA
    Science 320:1433-4. 2008
  8. pmc SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver
    Jay D Horton
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9046, USA
    J Clin Invest 109:1125-31. 2002
  9. pmc PCSK9: a convertase that coordinates LDL catabolism
    Jay D Horton
    Department of Internal Medicine, The Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390 9046, USA
    J Lipid Res 50:S172-7. 2009
    ....
  10. ncbi request reprint Compensatory increase in fatty acid synthesis in adipose tissue of mice with conditional deficiency of SCAP in liver
    Hiroshi Kuriyama
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    Cell Metab 1:41-51. 2005
    ..Plasma VLDL triglycerides are dramatically reduced in L-Scap- mice, underscoring the benefits of synthesizing FAs in fat rather than liver...
  11. ncbi request reprint Diminished hepatic response to fasting/refeeding and liver X receptor agonists in mice with selective deficiency of sterol regulatory element-binding protein-1c
    Guosheng Liang
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9046, USA
    J Biol Chem 277:9520-8. 2002
    ..Moreover, these mRNAs, as well as multiple other lipogenic mRNAs, showed a markedly blunted response to the LXR agonist T090137, indicating an essential role of SREBP-1c in the LXR response...
  12. pmc Overexpression of Insig-1 in the livers of transgenic mice inhibits SREBP processing and reduces insulin-stimulated lipogenesis
    Luke J Engelking
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, 75390, USA
    J Clin Invest 113:1168-75. 2004
    ..These results provide in vivo support for the hypothesis that nSREBPs are essential for high levels of lipid synthesis in the liver and indicate that Insig's modulate nSREBP levels by binding and retaining SCAP in the ER...
  13. pmc Schoenheimer effect explained--feedback regulation of cholesterol synthesis in mice mediated by Insig proteins
    Luke J Engelking
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9046, USA
    J Clin Invest 115:2489-98. 2005
    ..These studies indicate that the essential elements of the regulatory pathway for lipid synthesis function in liver as they do in cultured cells...
  14. ncbi request reprint LXRs regulate the balance between fat storage and oxidation
    Nada Y Kalaany
    Howard Hughes Medical Institute, Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA
    Cell Metab 1:231-44. 2005
    ..These studies suggest that, by selectively sensing the cholesterol component of a lipid-rich diet, LXRs govern the balance between storage and oxidation of dietary fat...
  15. pmc Decreased plasma cholesterol and hypersensitivity to statins in mice lacking Pcsk9
    Shirya Rashid
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390 9046, USA
    Proc Natl Acad Sci U S A 102:5374-9. 2005
    ..These data demonstrate that PCSK9 regulates the amount of LDLR protein in liver and suggest that inhibitors of PCSK9 may act synergistically with statins to enhance LDLRs and reduce plasma cholesterol...
  16. pmc Deletion of ELOVL5 leads to fatty liver through activation of SREBP-1c in mice
    Young Ah Moon
    Department of Molecular Genetics, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390 9046, USA
    J Lipid Res 50:412-23. 2009
    ..These studies demonstrate that reduced ELOVL5 activity leads to hepatic steatosis, and endogenously synthesized PUFAs are key regulators of SREBP-1c activation and fatty acid synthesis in livers of mice...
  17. ncbi request reprint Upregulation of hepatic LDL transport by n-3 fatty acids in LDL receptor knockout mice
    Chandna Vasandani
    Department of Internal Medicine, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390 8887, USA
    J Lipid Res 43:772-84. 2002
    ..In conclusion, these studies indicate that n-3 PUFA can markedly decrease the plasma concentration of apoB-containing lipoproteins and enhance hepatic LDL clearance through a mechanism that does not involve the LDLr pathway or LRP...
  18. ncbi request reprint Identification of two mammalian reductases involved in the two-carbon fatty acyl elongation cascade
    Young Ah Moon
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9046, USA
    J Biol Chem 278:7335-43. 2003
    ..Here, we report the identification and characterization of two mammalian enzymes that catalyze the 3-ketoacyl-CoA and trans-2,3-enoyl-CoA reduction reactions in long and very long chain fatty acid elongation, respectively...
  19. ncbi request reprint Post-transcriptional regulation of low density lipoprotein receptor protein by proprotein convertase subtilisin/kexin type 9a in mouse liver
    Sahng Wook Park
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9046, USA
    J Biol Chem 279:50630-8. 2004
    ..These data are consistent with PCSK9 affecting plasma LDL cholesterol levels by altering LDL receptor protein levels via a post-transcriptional mechanism...
  20. pmc Fasting reduces plasma proprotein convertase, subtilisin/kexin type 9 and cholesterol biosynthesis in humans
    Jeffrey D Browning
    Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA
    J Lipid Res 51:3359-63. 2010
    ..Inasmuch as cholesterol synthesis and PCSK9 are both regulated by SREBP-2, these results suggest that plasma PCSK9 levels may serve as a surrogate marker of hepatic SREBP-2 activity in humans...
  21. pmc Molecular mechanisms of hepatic steatosis and insulin resistance in the AGPAT2-deficient mouse model of congenital generalized lipodystrophy
    Víctor A Cortés
    Department of Molecular Genetics, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA
    Cell Metab 9:165-76. 2009
    ..These observations suggest that both dietary fat and hepatic triglyceride biosynthesis via a monoacylglycerol pathway may contribute to hepatic steatosis in Agpat2(-/-) mice...
  22. pmc Overexpression of ABCG5 and ABCG8 promotes biliary cholesterol secretion and reduces fractional absorption of dietary cholesterol
    Liqing Yu
    Department of Molecular Genetics and McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390 9046, USA
    J Clin Invest 110:671-80. 2002
    ....
  23. pmc Crystal structure of Spot 14, a modulator of fatty acid synthesis
    Christopher L Colbert
    Department of Biochemistry and Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390 9050, USA
    Proc Natl Acad Sci U S A 107:18820-5. 2010
    ..The structure of S14 suggests a mechanism whereby heterodimer formation with MIG12 attenuates the ability of MIG12 to activate ACC...
  24. pmc Deficiency of carbohydrate response element-binding protein (ChREBP) reduces lipogenesis as well as glycolysis
    Katsumi Iizuka
    Department of Biochemistry, University of Texas Southwestern Medical Center and Dallas Veterans Affairs Medical Center, 4500 South Lancaster Road, Dallas, TX 75216, USA
    Proc Natl Acad Sci U S A 101:7281-6. 2004
    ....
  25. pmc Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and in livers of parabiotic mice
    Thomas A Lagace
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Clin Invest 116:2995-3005. 2006
    ..We conclude that secreted PCSK9 associates with the LDLR and reduces hepatic LDLR protein levels...
  26. ncbi request reprint Catalytic activity is not required for secreted PCSK9 to reduce low density lipoprotein receptors in HepG2 cells
    Markey C McNutt
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Biol Chem 282:20799-803. 2007
    ..We conclude that the ability of PCSK9 to degrade LDLRs is independent of catalytic activity and suggest that PCSK9 functions as a chaperone to prevent LDLR recycling and/or to target LDLRs for lysosomal degradation...
  27. pmc Molecular mediators of hepatic steatosis and liver injury
    Jeffrey D Browning
    Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, 75390 9046, USA
    J Clin Invest 114:147-52. 2004
    ..Here we highlight recent advances in our understanding of the molecular events contributing to hepatic steatosis and nonalcoholic steatohepatitis...
  28. ncbi request reprint Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity
    Jeffrey D Browning
    Donald W Reynolds Cardiovascular Clinical Research Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390 9046, USA
    Hepatology 40:1387-95. 2004
    ..In conclusion, the significant ethnic and sex differences in the prevalence of hepatic steatosis documented in this study may have a profound impact on susceptibility to steatosis-related liver disease...
  29. pmc Induced polymerization of mammalian acetyl-CoA carboxylase by MIG12 provides a tertiary level of regulation of fatty acid synthesis
    Chai Wan Kim
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390 9046, USA
    Proc Natl Acad Sci U S A 107:9626-31. 2010
    ..Thus, in addition to its regulation by phosphorylation and transcription, ACC is regulated at a tertiary level by MIG12, which facilitates ACC polymerization and enhances enzymatic activity...
  30. pmc Genetic and metabolic determinants of plasma PCSK9 levels
    Susan G Lakoski
    Donald W Reynolds Cardiovascular Clinical Research Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9046, USA
    J Clin Endocrinol Metab 94:2537-43. 2009
    ..PCSK9 is present in human plasma, but the factors that contribute to differences in plasma concentrations of PCSK9 and how they impact on the levels of lipoproteins have not been well-characterized...
  31. pmc Antagonism of secreted PCSK9 increases low density lipoprotein receptor expression in HepG2 cells
    Markey C McNutt
    Departments of Molecular Genetics, Biochemistry, and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Biol Chem 284:10561-70. 2009
    ..These studies support the concept that pharmacological inhibition of the PCSK9-LDLR interaction extracellularly will increase hepatic LDLR expression and lower plasma low density lipoprotein levels...
  32. ncbi request reprint Cholesterol accumulation and liver cell death in mice with Niemann-Pick type C disease
    Eduardo P Beltroy
    Department of Pediatrics, University of Texas Southwestern Medical School, Dallas, TX 75390 8887, USA
    Hepatology 42:886-93. 2005
    ..In conclusion, the NPC mouse has liver disease similar to that seen in the NPC infant and represents a relevant model for exploring the molecular events occurring in this form of liver disease...
  33. ncbi request reprint Binding of proprotein convertase subtilisin/kexin type 9 to epidermal growth factor-like repeat A of low density lipoprotein receptor decreases receptor recycling and increases degradation
    Da Wei Zhang
    Department of Molecular Genetics, The Donald W Reynolds Cardiovascular Clinical Research Center, Howard Hughes Institute, University of Texas Southwestern Medical Center, Dallas 75390, USA
    J Biol Chem 282:18602-12. 2007
    ..As a consequence, the LDLR is rerouted from the endosome to the lysosome where it is degraded...
  34. pmc Molecular characterization of loss-of-function mutations in PCSK9 and identification of a compound heterozygote
    Zhenze Zhao
    Department of Molecular Genetics, University of Texas Southwestern Medical Center at Dallas, TX 75390, USA
    Am J Hum Genet 79:514-23. 2006
    ..The very low plasma level of LDL-C and apparent good health of this individual demonstrate that PCSK9 plays a major role in determining plasma levels of LDL-C and provides an attractive target for LDL-lowering therapy...
  35. pmc Plasma PCSK9 preferentially reduces liver LDL receptors in mice
    Aldo Grefhorst
    Department of Molecular Genetics, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390 9046, USA
    J Lipid Res 49:1303-11. 2008
    ....
  36. pmc Molecular basis for LDL receptor recognition by PCSK9
    Hyock Joo Kwon
    Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390 9050, USA
    Proc Natl Acad Sci U S A 105:1820-5. 2008
    ....
  37. pmc Therapeutic RNAi targeting PCSK9 acutely lowers plasma cholesterol in rodents and LDL cholesterol in nonhuman primates
    Maria Frank-Kamenetsky
    Alnylam Pharmaceuticals, 300 Third Street, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 105:11915-20. 2008
    ..These results validate PCSK9 targeting with RNAi therapeutics as an approach to specifically lower LDLc, paving the way for the development of PCSK9-lowering agents as a future strategy for treatment of hypercholesterolemia...
  38. pmc ATP-citrate lyase deficiency in the mouse
    Anne P Beigneux
    Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA 94141, USA
    J Biol Chem 279:9557-64. 2004
    ..The Acly knockout allele is useful for identifying cell types with a high demand for acetyl-CoA synthesis...
  39. pmc Effective RNAi-mediated gene silencing without interruption of the endogenous microRNA pathway
    Matthias John
    Alnylam Europe AG, Fritz Hornschuch Str 9, 95326 Kulmbach, Germany
    Nature 449:745-7. 2007
    ..This study advances the use of siRNAs as safe and effective tools to silence gene transcripts in animal studies, and supports the continued advancement of RNA interference therapeutics using synthetic siRNA...

Research Grants10

  1. Characterization of Microsomal Fatty Acid Elongation
    JAY HORTON; Fiscal Year: 2007
    ..abstract_text> ..
  2. Pathogenesis of Obesity and Metabolic Syndrome
    JAY HORTON; Fiscal Year: 2006
    ....
  3. Taskforce for Obesity Research at Southwestern (RMI)
    JAY HORTON; Fiscal Year: 2006
    ....
  4. DIET, HDL, AND REVERSE CHOLESTEROL TRANSPORT
    JAY HORTON; Fiscal Year: 2003
    ..abstract_text> ..