Characterization of a new fatty acid response element that controls the expression of the locust muscle FABP gene

  • Qiwei Wu
  • Weihua Chang
  • Jutta Rickers-Haunerland
  • Tobi Higo
  • Norbert H. Haunerland
Part of the Developments in Molecular and Cellular Biochemistry book series (DMCB, volume 38)


In vertebrate and invertebrate muscles, the expression of fatty acid binding proteins (FABP) is induced by long chain fatty acids. To identify the fatty acid response elements that mediate this up-regulation, the gene of the FABP expressed in locust flight muscle was cloned, and its upstream sequences analyzed for potential regulatory elements. Comparison with other muscle FABP promoters revealed the presence of a 19-bp imperfect inverted repeat sequence that contains two hexanucleotide half sites (AGTGGT and ATGGGA), interspersed by 3 nucleotides. The promoter activity was studied with reporter gene constructs in L6 myoblasts, in which H-FABP expression is stimulated by long-chain fatty acids in a similar manner as in adult cardio- myocytes. The 19 bp element, located 180 bp upstream of the transcription start site, was found to be essential for the fatty acid induction of gene expression, and gel shift analysis confirmed that this fatty acid response element is capable of binding nu- clear proteins both from rat myoblasts and locust muscle in the presence of fatty acids. A similar, but reverse sequence that is present upstream of all mammalian H-FABP promoters may modulate the expression of the rat H-FABP gene. (Mol Cell Biochem 239: 173–180,2002)

Key words

fatty acid binding protein fatty acid response element FARE Schistocerca gregaria inverted repeat everted repeat gene regulation gel shift 



fatty acid binding protein

L-,A- and H-FABP

liver-,adipocyte and heart-FABP


fatty acid response element


peroxisome proliferator activated receptor


peroxisome proliferator response element


direct repeat separated by 1 nucleotide


inverted repeat separated by 3 nucleotides;


everted repeat separated by 3 nucleotides


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  1. 1.
    Vogel Hertzcl A, Bernlohr DA: The mammalian fatty acid-binding protein multigenc family: Molecular and genetic insights into function. Trends Endocrinol Metab 11: 175–180, 2000CrossRefGoogle Scholar
  2. 2.
    Vecrkamp JH, van Mocrkerk HTB: Fatty acid binding protein and its relation to fatty acid oxidation. Mol Cell Biochem 123: 101–106, 1993CrossRefGoogle Scholar
  3. 3.
    van Breda E, Keizer HA, Vork VIM, Surtel DAM, de Jong YF, van der Vusse GJK, Glatz JFC: Modulation of fatty-acid-binding protein content of rat heart and skeletal muscle by endurance training and testosterone treatment. Pflü gers Arch 421: 274–279, 1992CrossRefGoogle Scholar
  4. 4.
    Guglielmo CG, Hauncrland NH, Williams TD: Fatty acid binding protein, a major protein in the flight muscle of migrating Western Sandpipers. Comp Biochem Physiol 119B: 549-555, 1998Google Scholar
  5. 5.
    Chen X, Haunerland NH: Fatty acid binding protein expression in locust flight muscle. Induction by flight, adipokinetic hormone, and low density lipophorin. Insect Biochem 24: 573–579, 1994CrossRefGoogle Scholar
  6. 6.
    Glatz JF, van Breda E, K.eizer HA, de Jong YF, Lakey JR, Rajotte RV, Thompson A, van der Vusse G.J, Lopaschuk GD: Rat heart fatty acid-binding protein content is increased in experimental diabetes. Biochem Biophys Res Commun 199: 639–646, 1994PubMedCrossRefGoogle Scholar
  7. 7.
    Van Bilsen M, de Vries JE, van der Vusse GJ: Long-term effects of fatty acids on cell viability and gene expression of neonatal cardiac myocytes. Prostaglandins Leukotrienes Essent Fatty Acids 57: 39–45, 1997CrossRefGoogle Scholar
  8. 8.
    van der Lee KA, Vork MM, De Vries JE, Willemsen PIT, Glatz JF. Reneman RS, van der Vusse GJ, van Bilsen M: Long-chain fatty acid-induced changes in gene expression in neonatal cardiac myocytes. J Lipid Res41: 41-47, 2000Google Scholar
  9. 9.
    van Bilsen M, van der Vusse GJ, Reneman RS: Transcriptional regulation of metabolic processes: Implications for cardiac metabolism. Pflügers Archs 437: 2–14, 1998CrossRefGoogle Scholar
  10. 10.
    Mangclsdorf DJ, Thummel C, Beato M, Herrlich P, Schutz G, Umesono K, Blumberg B, Kastner P, Mark M, Chambon P et al.: The nuclear receptor superfamily: The second decade. Cell 83: 835–839, 1995CrossRefGoogle Scholar
  11. 11.
    Wolfrum C, Ellinghaus P, Fobker M, Sccdorf U, Assmann G, Börchers T, Spencr F: Phytanic acid is ligand and transcriptional activator of murine liver fatty acid binding protein. J Lipid Res 40: 708–714, 1999PubMedGoogle Scholar
  12. 12.
    Frohnert BI, Hui TY, Bernlohr DA: Identification of a functional peroxisome proliferator-responsive element in the murine fatty acid transport protein gene. J Biol Chcm 274: 3970–3977, 1999CrossRefGoogle Scholar
  13. 13.
    Braissant O, Foufclle F, Scotto C, Dauca M, Wahli W: Differential expression of peroxisome proliferator-activated receptors (PPARs): Tissue distribution of PPAR-alpha.-beta, and-gamma in the adult rat. Endocrinology 137: 354–366, 1996PubMedCrossRefGoogle Scholar
  14. 14.
    Zhang J, Rickers-Haunerland J, Dawe I, Haunerland, NH: Structure and chromosomal location of the rat gene encoding the heart fatty acid-binding protein. Eur J Biochem 266: 347–351. 1999PubMedCrossRefGoogle Scholar
  15. 15.
    Wu Q, Andolfatto P, Haunerland NH: Cloning and sequence of the gene encoding the muscle fatty acid binding protein from the desert locust. Schislocerca gregaria. Insect Biochem Mol Biol 31: 553–562, 2001PubMedCrossRefGoogle Scholar
  16. 16.
    Rodriguez B, Scvcrson D: Preparation of cardiomyocytes. In: J.H. McNeill (ed). Biochemical Techniques in the Heart. CRC Press, Boca Raton, FL, 1997, pp 101–115Google Scholar
  17. 17.
    Chang W, Rickers-Haunerland J, Haunerland NH: Induction of cardiac FABP gene expression by long chain fatty acids in cultured rat muscle cells. Mol Cell Biochem 221: 127–132, 2001PubMedCrossRefGoogle Scholar
  18. 18.
    Wu Q, Haunerland NH: A novel fatty acid response element controls the expression of the flight muscle FABP gene of the desert locust, Schistocerca gregaria. Eur J Biochem 268: 5894–5900, 2001PubMedCrossRefGoogle Scholar
  19. 19.
    Haunerland NH, Andolfatto P, Chisholm JM, Wang Z, Chen X: Fatty acid binding protein in locust flight muscle. Developmental changes of expression, concentration, and intracellular distribution. Eur J Biochem 210: 1045–1051, 1992PubMedCrossRefGoogle Scholar
  20. 20.
    Wolfrum C, Borrmann CM, Börchers T, Spener F: Fatty acids and hypolipidemic drugs regulate peroxisome proliferator-activated receptors alpha —and gamma-mediated gene expression via liver fatty acid binding protein: A signaling path to the nucleus. Proc Natl Acad Sci USA 98: 2323–2328, 2001PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2002

Authors and Affiliations

  • Qiwei Wu
    • 1
  • Weihua Chang
    • 1
  • Jutta Rickers-Haunerland
    • 1
  • Tobi Higo
    • 1
  • Norbert H. Haunerland
    • 1
    • 2
  1. 1.Department of Biological SciencesSimon Fraser UniversityBurnabyCanada
  2. 2.Department of Biological SciencesSimon Fraser UniversityBurnabyCanada

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