Display options
Cite
Rakhshandehroo M, Sanderson LM, Matilainen M, et al. Comprehensive analysis of PPARalpha-dependent regulation of hepatic lipid metabolism by expression profiling. PPAR Res. 2007;2007:26839doi: 10.1155/2007/26839.
Rakhshandehroo, M., Sanderson, L. M., Matilainen, M., Stienstra, R., Carlberg, C., de Groot, P. J., Müller, M., & Kersten, S. (2007). Comprehensive analysis of PPARalpha-dependent regulation of hepatic lipid metabolism by expression profiling. PPAR research, 200726839. https://doi.org/10.1155/2007/26839
Rakhshandehroo, Maryam, et al. "Comprehensive analysis of PPARalpha-dependent regulation of hepatic lipid metabolism by expression profiling." PPAR research vol. 2007 (2007): 26839. doi: https://doi.org/10.1155/2007/26839
Rakhshandehroo M, Sanderson LM, Matilainen M, Stienstra R, Carlberg C, de Groot PJ, Müller M, Kersten S. Comprehensive analysis of PPARalpha-dependent regulation of hepatic lipid metabolism by expression profiling. PPAR Res. 2007;2007:26839. doi: 10.1155/2007/26839. PMID: 18288265; PMCID: PMC2233741.
Copy Download .nbib Format: NLM
Share it on

PPAR Res. 2007;2007:26839. doi: 10.1155/2007/26839.

Comprehensive analysis of PPARalpha-dependent regulation of hepatic lipid metabolism by expression profiling.

PPAR research

Maryam Rakhshandehroo, Linda M Sanderson, Merja Matilainen, Rinke Stienstra, Carsten Carlberg, Philip J de Groot, Michael Müller, Sander Kersten

Affiliations

  1. Nutrigenomics Consortium, Wageningen Centre for Food Sciences, Wageningen, The Netherlands.

PMID: 18288265 PMCID: PMC2233741 DOI: 10.1155/2007/26839

Abstract

PPARalpha is a ligand-activated transcription factor involved in the regulation of nutrient metabolism and inflammation. Although much is already known about the function of PPARalpha in hepatic lipid metabolism, many PPARalpha-dependent pathways and genes have yet to be discovered. In order to obtain an overview of PPARalpha-regulated genes relevant to lipid metabolism, and to probe for novel candidate PPARalpha target genes, livers from several animal studies in which PPARalpha was activated and/or disabled were analyzed by Affymetrix GeneChips. Numerous novel PPARalpha-regulated genes relevant to lipid metabolism were identified. Out of this set of genes, eight genes were singled out for study of PPARalpha-dependent regulation in mouse liver and in mouse, rat, and human primary hepatocytes, including thioredoxin interacting protein (Txnip), electron-transferring-flavoprotein beta polypeptide (Etfb), electron-transferring-flavoprotein dehydrogenase (Etfdh), phosphatidylcholine transfer protein (Pctp), endothelial lipase (EL, Lipg), adipose triglyceride lipase (Pnpla2), hormone-sensitive lipase (HSL, Lipe), and monoglyceride lipase (Mgll). Using an in silico screening approach, one or more PPAR response elements (PPREs) were identified in each of these genes. Regulation of Pnpla2, Lipe, and Mgll, which are involved in triglyceride hydrolysis, was studied under conditions of elevated hepatic lipids. In wild-type mice fed a high fat diet, the decrease in hepatic lipids following treatment with the PPARalpha agonist Wy14643 was paralleled by significant up-regulation of Pnpla2, Lipe, and Mgll, suggesting that induction of triglyceride hydrolysis may contribute to the anti-steatotic role of PPARalpha. Our study illustrates the power of transcriptional profiling to uncover novel PPARalpha-regulated genes and pathways in liver.

References

  1. Nature. 2000 May 25;405(6785):421-4 - PubMed
  2. Liver Int. 2006 Jun;26(5):613-20 - PubMed
  3. Hepatology. 1990 Sep;12(3 Pt 1):511-8 - PubMed
  4. Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7473-8 - PubMed
  5. Ann N Y Acad Sci. 2002 Jun;967:7-18 - PubMed
  6. Genes Dev. 2002 Jan 1;16(1):27-32 - PubMed
  7. J Biol Chem. 2002 Feb 15;277(7):4806-15 - PubMed
  8. Am J Pathol. 2006 Sep;169(3):846-60 - PubMed
  9. Biochemistry. 1985 Jul 16;24(15):3913-21 - PubMed
  10. Cell. 2003 Apr 18;113(2):159-70 - PubMed
  11. Bioinformatics. 2005 Sep 15;21(18):3637-44 - PubMed
  12. Cell Mol Life Sci. 2004 Feb;61(4):393-416 - PubMed
  13. Am J Physiol Gastrointest Liver Physiol. 2005 Sep;289(3):G456-61 - PubMed
  14. Endocr Rev. 1999 Oct;20(5):649-88 - PubMed
  15. Biochem Soc Trans. 1997 Nov;25(4):1242-8 - PubMed
  16. J Biol Chem. 2003 Oct 17;278(42):40688-93 - PubMed
  17. Nucleic Acids Res. 2005 Nov 10;33(20):e175 - PubMed
  18. Mol Cell. 2002 Oct;10(4):721-33 - PubMed
  19. J Clin Invest. 2003 Feb;111(3):357-62 - PubMed
  20. J Clin Invest. 2003 Feb;111(3):347-55 - PubMed
  21. Science. 2006 May 5;312(5774):734-7 - PubMed
  22. J Clin Invest. 2004 Jul;114(1):94-103 - PubMed
  23. J Lipid Res. 2005 Jan;46(1):123-34 - PubMed
  24. J Nutr. 2004 Jun;134(6):1475-80 - PubMed
  25. Biochem Soc Trans. 1988 Jun;16(3):416-8 - PubMed
  26. J Biol Chem. 1999 Aug 13;274(33):23341-8 - PubMed
  27. J Biol Chem. 2004 Apr 16;279(16):16154-60 - PubMed
  28. Annu Rev Pharmacol Toxicol. 2005;45:1-25 - PubMed
  29. J Clin Invest. 1999 Jun;103(11):1489-98 - PubMed
  30. Nat Rev Genet. 2006 Jan;7(1):55-65 - PubMed
  31. Endocrinology. 2006 Sep;147(9):4517-24 - PubMed
  32. Eur J Pharmacol. 2006 Apr 24;536(1-2):182-91 - PubMed
  33. Annu Rev Cell Dev Biol. 2000;16:145-71 - PubMed
  34. FEBS Lett. 2000 May 19;473(3):333-6 - PubMed
  35. J Biol Chem. 2004 Nov 19;279(47):48968-75 - PubMed
  36. Biochim Biophys Acta. 2003 Nov 30;1635(1):29-36 - PubMed
  37. Genes Dev. 2002 Jan 1;16(1):22-6 - PubMed
  38. J Endocrinol. 2001 Jun;169(3):453-9 - PubMed
  39. Nat Genet. 2002 Jan;30(1):110-6 - PubMed
  40. Curr Opin Gastroenterol. 2004 Nov;20(6):572-80 - PubMed
  41. J Biol Chem. 2001 Oct 19;276(42):39088-93 - PubMed
  42. PLoS Biol. 2004 Oct;2(10):e294 - PubMed
  43. Nat Med. 2004 Apr;10(4):355-61 - PubMed
  44. Science. 2004 Nov 19;306(5700):1383-6 - PubMed
  45. J Lipid Res. 2002 Jun;43(6):921-9 - PubMed

Publication Types