Abstract
The heart is the most fatty acid-dependent muscle in mammals, but flight muscles of birds and insects encounter even higher rates of fatty acid oxidation. The amount of the muscle fatty acid binding protein (H-FABP) found in these muscle reflects their metabolic activities, and increased fatty acid metabolism in endurance exercise increases FABP expression further. We have studied the mechanism of fatty acid-dependent expression of the H-FABP gene, taking advantage of the comparative analysis of gene control in functionally related, but evolutionary distant animal systems, i.e., rat heart and locust flight muscle. Luciferase reporter genes with a full-length promoter (∼1 kb) from either the locust or the rat were strongly expressed in L6 myoblasts, and the expression of both constructs was markedly increased by fatty acid treatment. Because of its stronger induction by fatty acids and the absence of other vertebrate transcription factor binding sites, the locust promoter was advantageous for the identification of a fatty acid response element (FARE), an inverted repeat of a hexanucleotide half site reminiscent of steroid hormone receptor binding sites (IR-3). All mammalian H-FABP promoters contain similar sequences, however in reverse orientation (everted repeats, ER-3). Deletion of the FARE eliminated the fatty acid inducibility completely for the locust promoter, but only partly for its mammalian analogue, perhaps because of additional factors or more complex interactions. In gel shift studies, the element binds nuclear proteins from both rat cells and locust flight muscle, further attesting to the far-reaching conservation of this mechanism. Two individual proteins bind to the element, with full binding requiring the presence of free fatty acid. Antibodies to PPARs failed to induce a supershift of the protein-DNA complex, indicating that other transcription factors are responsible for the fatty acid-mediated induction of gene expression of H-FABP.
Similar content being viewed by others
References
Duttaroy AK, Spener F (eds): Cellular proteins and their fatty acids in health and disease. Wiley-VCH: Weinheim, p. 460, 2003
Stahl A: A current review of fatty acid transport proteins (SLC27). Eur J Physiol 447: 722–727, 2003
Bonen A, Miskovic D, Kiens B: Fatty acid transporters (FABPpm, FAT, FATP) in human muscle. Can J Appl Physiol Rev Can Physiol Appl 24: 515–523, 1999
Crabtree B, Newsholme EA: Comparative aspects of fuel utilization and metabolism by muscle. In: Usherwood PNR (ed). Insect muscle. Academic Press, London, pp. 405–491, 1975
Haunerland NH, Spener F: Properties and physiological significance of fatty acid binding proteins. In: van der Vusse GJ (ed). Lipobiology, Elsevier, pp. 99–123, 2004
Haunerland NH: Transport and utilization in insect flight muscles. Comp Biochem Physiol B 117: 475–482, 1997
Butler PJ, Woakes AJ: The physiology of bird flight. In: Gwinner E (ed). Bird migration: Physiology and Ecophysiology, Springer, Berlin, pp. 300–318, 1990
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, 2001
Zhang J, Haunerland NH: Transcriptional regulation of FABP expression in flight muscle of the desert locust, Schistocerca gregaria. Insect Biochem Mol Biol 28: 683–691, 1998
Wu QW, Chang WH, Rickers-Haunerland J, Higo T, Haunerland NH: Characterization of a new fatty acid response element that controls the expression of the locust muscle FABP gene. Mol Cell Biochem 239: 173–180, 2002
Wu QW 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, 2001
Wilson H: Western Sandpiper (Calidris mauri). In: Poole A, Gill F (eds). The birds of North America. Academy of Natural Sciences, Philadelphia, 1994
Guglielmo CG, Haunerland NH, Hochachka PW, Williams TD: Seasonal dynamics of flight muscle fatty acid binding protein and catabolic enzymes in a migratory shorebird. Am J Physiol 282: R1405–R1413, 2002
Haunerland NH, Andolfatto P, Chisholm JM, Wang ZX, Chen XM: Fatty acid binding protein in locust flight muscle – Developmental changes of expression, concentration and intracellular distribution. Eur J Biochem 210: 1045–1051, 1992
Clavel S, Farout L, Briand M, Briand Y, Jouanel P: Effect of endurance training and/or fish oil supplemented diet on cytoplasmic fatty acid binding protein in rat skeletal muscles and heart. Eur J Appl Physiol 87: 193–201, 2002
Veerkamp JH, Van Moerkerk HTB: Fatty acid binding protein and its relation to fatty acid oxidation. Mol Cell Biochem 123: 101–106, 1993
Glatz JFC, Van Breda E, Keizer HA, Dejong YF, Lakey JRT, Rajotte RV, Thompson A, Vandervusse GJ, Lopaschuk GD: Rat heart fatty acid binding protein content is increased in experimental diabetes. Biochem Biophys Res Commun 199: 639–646, 1994
Chen XM, Haunerland NH: Fatty acid binding protein expression in locust flight-muscle – induction by flight, adipokinetic hormone, and low-density lipophorin. Insect Biochem Mol Biol 24: 573–579, 1994
Duplus E, Glorian M, Forest C: Fatty acid regulation of gene transcription. J Biol Chem 275: 30749–30752, 2000
Bernlohr DA, Coe NR, Simpson MA, Hertzel AV: Regulation of gene expression in adipose cells by polyunsaturated fatty acids. Adv Exp Med Biol 422: 145–156, 1997
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, 2001
Schachtrup C, Emmler T, Bleck B, Sandqvist A, Spener F: Functional analysis of peroxisome-proliferator-responsive element motifs in genes of fatty acid-binding proteins. Biochem J 382: 239–245, 2004
Owen GI, Zelent A: Origins and evolutionary diversification of the nuclear receptor superfamily. Cell Mol Life Sci 57: 809–827, 2000
Ahuja HS, Szanto A, Nagy L, Davies PJ: The retinoid X receptor and its ligands: versatile regulators of metabolic function, cell differentiation and cell death. J Biol Regul Homeost Agents 17: 29–45, 2003
Wolfrum C, Spener F: Cross-talk between Intracellular Lipid Binding Proteins and Ligand Activated Nuclear Receptors – A Signaling Pathway for Fatty Acids. In: A. Duttaroy, F. Spener (eds). Cellular Proteins and their Fatty Acids in Health and Disease. Wiley-VCH, Weinheim, Germany, pp. 267–284, 2003
Hayward DC, Dhadialla TS, Zhou S, Kuiper MJ, Ball EE, Wyatt GR, Walker VK: Ligand specificity and developmental expression of RXR and ecdysone receptor in the migratory locust. J Insect Physiol 49: 1135–1144, 2003
Van Breda E, Keizer HA, Vork MM, Surtel DAM, Dejong YF, Van der Vusse GJ, Glatz JFC: Modulation of fatty acid binding protein content of rat heart and skeletal muscle by endurance training and testosterone treatment. Eur J Physiol 421: 274–279, 1992
Carey JO, Neufer PD, Farrar RP, Veerkamp JH, Dohm GL: Transcriptional regulation of muscle fatty acid binding protein. Biochem J 298: 613–617, 1994
Pelsers MMAL, Butler PJ, Bishop CM, Glatz JFC: Fatty acid binding protein in heart and skeletal muscles of the migratory barnacle goose throughout development. Am J Physiol 276: R637–R643, 1999
van der Lee KAJM, Vork MM, De Vries JE, Willemsen PHM, Glatz JFC, Reneman RS, Van der Vusse GJ, Van Bilsen M: Long-chain fatty acid-induced changes in gene expression in neonatal cardiac myocytes. J Lipid Res 41: 41–47, 2000
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Qu, H., Cui, L., Rickers-Haunerland, J. et al. Fatty acid-dependent expression of the muscle FABP gene – comparative analysis of gene control in functionally related, but evolutionary distant animal systems. Mol Cell Biochem 299, 45–53 (2007). https://doi.org/10.1007/s11010-005-9036-z
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11010-005-9036-z