Skip to main content
SpringerLink
Log in

Role of Fatty Acid Binding Proteins and Long Chain Fatty Acids in Modulating Nuclear Receptors and Gene Transcription

  • Review
  • Published:
Lipids

Abstract

Abnormal energy regulation may significantly contribute to the pathogenesis of obesity, diabetes mellitus, cardiovascular disease, and cancer. For rapid control of energy homeostasis, allosteric and posttranslational events activate or alter activity of key metabolic enzymes. For longer impact, transcriptional regulation is more effective, especially in response to nutrients such as long chain fatty acids (LCFA). Recent advances provide insights into how poorly water-soluble lipid nutrients [LCFA; retinoic acid (RA)] and their metabolites (long chain fatty acyl Coenzyme A, LCFA-CoA) reach nuclei, bind their cognate ligand-activated receptors, and regulate transcription for signaling lipid and glucose catabolism or storage: (i) while serum and cytoplasmic LCFA levels are in the 200 μM–mM range, real-time imaging recently revealed that LCFA and LCFA-CoA are also located within nuclei (nM range); (ii) sensitive fluorescence binding assays show that LCFA-activated nuclear receptors [peroxisome proliferator-activated receptor-α (PPARα) and hepatocyte nuclear factor 4α (HNF4α)] exhibit high affinity (low nM K d s) for LCFA (PPARα) and/or LCFA-CoA (PPARα, HNF4α)—in the same range as nuclear levels of these ligands; (iii) live and fixed cell immunolabeling and imaging revealed that some cytoplasmic lipid binding proteins [liver fatty acid binding protein (L-FABP), acyl CoA binding protein (ACBP), cellular retinoic acid binding protein-2 (CRABP-2)] enter nuclei, bind nuclear receptors (PPARα, HNF4α, CRABP-2), and activate transcription of genes in fatty acid and glucose metabolism; and (iv) studies with gene ablated mice provided physiological relevance of LCFA and LCFA-CoA binding proteins in nuclear signaling. This led to the hypothesis that cytoplasmic lipid binding proteins transfer and channel lipidic ligands into nuclei for initiating nuclear receptor transcriptional activity to provide new lipid nutrient signaling pathways that affect lipid and glucose catabolism and storage.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

LCFA:

Long chain fatty acids

L-FCFA-CoA:

Long chain fatty acyl Coenzyme A

L-FABP:

Liver fatty acid binding protein

A-FABP:

Adipocyte FABP

H-FABP:

Heart FABP

K-FABP:

Keratinocyte FABP

I-FABP:

Intestinal FABP

B-FABP:

Brain FABP

ACBP:

Acyl CoA binding protein

CRABP:

Cellular retinoic acid binding protein

PPAR:

Peroxisome proliferator-activated receptor

HNF4α:

Hepatocyte nuclear factor-4α

RA:

Retinoic acid

RXR:

Retinoic acid X receptor

SCP-2:

Sterol carrier protein-2

WT:

Wild-type

References

  1. Lin Q, Ruuska SE, Shaw NS, Dong D, Noy N (1999) Ligand selectivity of the peroxisome proliferator-activated receptor α. Biochem 38:185–190

    CAS  Google Scholar 

  2. Hostetler HA, Petrescu AD, Kier AB, Schroeder F (2005) Peroxisome proliferator-activated receptor α interacts with high affinity and is conformationally responsive to endogenous ligands. J Biol Chem 280:18667–18682

    PubMed  CAS  Google Scholar 

  3. Hostetler HA, Kier AB, Schroeder F (2006) Very-long-chain and branched-chain fatty acyl-CoAs are high affinity ligands for the peroxisome proliferator-activated receptor α (PPARα). Biochemistry 45:7669–7681

    PubMed  CAS  Google Scholar 

  4. Adida A, Spener F (2002) Intracellular lipid binding proteins and nuclear receptors inolved in branched-chain fatty acid signaling. Prost Leukot Essen Fatty Acids 67:91–98

    CAS  Google Scholar 

  5. Desvergne B, Michalik L, Wahli W (2004) Be fit or be sick: peroxisome proliferator-activated receptors are down the road. Mol Endocrinol 18:1321–1332

    PubMed  CAS  Google Scholar 

  6. Frederiksen KS, Wulf EM, Wassermann K, Sauerberg P, Fleckner J (2003) Identification of hepatic transcriptional changes in insulin-resistant rats treated with peroxisome proliferator activated receptor-α agonists. J Mol Endocrinol 30:317–329

    PubMed  CAS  Google Scholar 

  7. Francis GA, Fayard E, Picard F, Auwerx J (2003) Nuclear receptors and the control of metabolism. Annu Rev Physiol 65:261–311

    PubMed  CAS  Google Scholar 

  8. Schoonjans K, Staels B, Auwerx J (1996) Role of the peroxisome proliferator-activated receptor (PPAR) in mediating the effects of fibrates and fatty acids on gene expression. J Lipid Res 37:907–925

    PubMed  CAS  Google Scholar 

  9. Jump DB (2004) Fatty acid regulation of gene transcription. Crit Rev Clin Lab Sci 41:41–78

    PubMed  CAS  Google Scholar 

  10. Pawar A, Jump DB (2003) Unsaturated fatty acid regulation of peroxisome proliferator activated receptor α activity in primary rat hepatocytes. J Biol Chem 278:35931–35939

    PubMed  CAS  Google Scholar 

  11. Jump DB, Clarke SD (1999) Regulation of gene expression by dietary fat. Annu Rev Nutr 19:63–90

    PubMed  CAS  Google Scholar 

  12. Kersten S, Desvergne B, Wahli W (2000) Roles of PPARs in health and disease. Nature 405:421–424

    PubMed  CAS  Google Scholar 

  13. Kersten S, Seydoux J, Peters JM, Gonzalex FJ, Desvergne B, Wahli W (1999) Peroxisome proliferator-activated receptor α mediates the adaptive response to fasting. J Clin Inv 103:1489–1498

    CAS  Google Scholar 

  14. Gottlicher M, Widmark E, Li Q, Gustafsson JA (1992) Fatty acids activate a chimera of the clofibric acid-activated receptor and the glucocorticoid receptor. Proc Natl Acad Sci 89:4653–4657

    PubMed  CAS  Google Scholar 

  15. Forman BM, Chen J, Evans RM (1999) Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors alpha and delta. Proc Natl Acad Sci 94:4312–4317

    Google Scholar 

  16. Keller H, Dreyer C, Medin J, Mahfoudi A, Ozato K, Wahli W (1993) Fatty acids and retinoids control lipid metabolism through activation of peroxisome proliferator activated receptorretinoid X receptor heterodimers. Proc Natl Acad Sci 90:2160–2164

    PubMed  CAS  Google Scholar 

  17. Kliewer SA, Sundseth SS, Jones SA, Brown PJ, Wisely GB, Koble CS, Devchand P, Wahli W, Willson TM, Lenhard JM, Lehmann JM (1997) Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors α and γ. Proc Natl Acad Sci 94:4318–4323

    PubMed  CAS  Google Scholar 

  18. Wolfrum C, Borrmann CM, Borchers T, Spener F (2001) Fatty acids and hypolipidemic drugs regulate PPARα and PPARγ gene expression via L-FABP: a signaling path to the nucleus. Proc Natl Acad Sci 98:2323–2328

    PubMed  CAS  Google Scholar 

  19. Krey G, Braissant O, L’Horset F, Kalkhoven E, Perroud M, Parker MG, Wahli W (1997) Fatty acids, eicosanoids, and hypolipidemic agents identified as ligands of peroxisome proliferator-activated receptors by coactivator-dependent receptor ligand assay. Mol Endocrinol 11:779–791

    PubMed  CAS  Google Scholar 

  20. Banner CD, Gottlicher M, Widmark E, Sjovall J, Rafter JJ, Gustafsson J (1993) A systematic analytical chemistry/cell assay approach to isolate activators of orphan nuclear receptors from biological extracts: characterization of peroxisome proliferator-activated receptor activators in plasma. J Lipid Res 34:1583–1591

    PubMed  CAS  Google Scholar 

  21. Bonilla S, Redonnet A, Noel-Suberville C, Pallet V, Garcin H, Higueret P (2000) High-fat diets affect the expression of nuclear retinoic acid receptor in rat liver. Br J Nutr 83:665–671

    Article  PubMed  CAS  Google Scholar 

  22. Xu J, Nawaz Z, Tsai SY, Tsai MJ, O’Malley BW (1996) The extreme C terminus of the progesterone receptor contains a transcriptional repressor domain that functions through a putative corepressor. Proc Natl Acad Sci USA 93:12195–12199

    PubMed  CAS  Google Scholar 

  23. Escher P, Wahli W (2000) Peroxisome proliferator activated receptors: insights into multiple cellular functions. Mutat Res 448:121–138

    PubMed  CAS  Google Scholar 

  24. Petrescu AD, Hertz R, Bar-Tana J, Schroeder F, Kier AB (2002) Ligand specificity and conformational dependence of the hepatic nuclear factor-4α (HNF-4α). J Biol Chem 277:23988–23999

    PubMed  CAS  Google Scholar 

  25. Svensson S, Osteberg T, Jacobsson M, Norstrom C, Stefansson K, Hallen D, Johansson IC, Zachrisson K, Ogg D, Jendeberg L (2003) Crystal structure of the heterodimeric complex of LXRα and RXRβ ligand binding domains in a fully agonistic form. EMBO J 22:4625–4633

    PubMed  CAS  Google Scholar 

  26. McGarry JD, Dobbins RL (1999) Fatty acids, lipotoxicity, and insulin secretion. Diabetologia 42:128–138

    PubMed  CAS  Google Scholar 

  27. Gossett RE, Frolov AA, Roths JB, Behnke WD, Kier AB, Schroeder F (1996) Acyl-CoA binding proteins: multiplicity and function. Lipids 31:895–918

    PubMed  CAS  Google Scholar 

  28. Lemberger T, Desvergne B, Wahli W (1996) Peroxisome proliferator-activated receptors. Annu Rev Cell Dev Biol 12:335–363

    PubMed  CAS  Google Scholar 

  29. Zomer AWM, van der Burg B, Jansen GA, Wanders RJA, Poll-The BT, van der Saag PT (2000) Pristanic acid and phytanic acid: naturally occurring ligands for the nuclear receptor peroxisome proliferator-activated receptor α. J Lipid Res 41:1801–1807

    PubMed  CAS  Google Scholar 

  30. Wolfrum C, Spener F (2000) Fatty acids as regulators in lipid metabolism. Eur J Lip Sci Technol 102:746–762

    CAS  Google Scholar 

  31. Hanhoff T, Wolfrum C, Ellinghaus P, Seedorf U, Spener F (2001) Pristanic acid is activator of peroxisome proliferator activated receptor alpha. Eur J Lipid Sci 103:75–80

    CAS  Google Scholar 

  32. Steinberg D (1995) Refsums disease. In: Scriver CR, Beaudet AL, Sly WS, Vallee D (eds) The metabolic and molecular basis of inherited disease. McGraw-Hill, New York

    Google Scholar 

  33. Reddy JK, Goel SK, Nemali MR, Crrino JJ, Laffler TG, Reddy MK, Sperbeck SJ, Osumi T, Hashimoto T, Lalwani ND, Rao MS (1986) Transcriptional regulation of peroxisomal fatty acyl-CoA oxidase and enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase in rat liver by peroxisome proliferators. Proc Natl Acad Sci 83:1747–1751

    PubMed  CAS  Google Scholar 

  34. Berge R, Stensland E, Aarsland A, Tsegai G, Osmundsen H, Aarsaether N, Gjellesvik DR (1987) Induction of cytosolic clofibroyl-CoA hydrolase activity in liver of rats treated with clofibrate. Biochim Biophys Acta 918:60–66

    PubMed  CAS  Google Scholar 

  35. Aarsland A, Berge RK (1991) Peroxisome proliferating sulphur and oxy-substituted fatty acid analogues are activated to acyl coenzyme A thioesters. Biochem Pharmacol 41:53–61

    PubMed  CAS  Google Scholar 

  36. Hertz R, Bar-Tana J (1987) Prevention of peroxisomal proliferation by carnitine palmitoyltransferase inhibitors in cultured rat hepatocytes and in vivo. Biochem J 245:387–392

    PubMed  CAS  Google Scholar 

  37. Fan CY, Pan J, Usuda N, Yeldandi AV, Rao MS, Reddy JK (1998) Steatohepatitis, spontaneous peroxisome proliferation and liver tumors in mice lacking peroxisomal fatty acyl-CoA oxidase. J Biol Chem 273:15639–15645

    PubMed  CAS  Google Scholar 

  38. Reddy JK, Hashimoto T (2001) Peroxisomal β-oxidation and peroxisome proliferatoractivated receptor α: an adaptive metabolic system. Annu Rev Nutr 21:193–230

    PubMed  CAS  Google Scholar 

  39. Grundy SM, Denke MA (1990) Dietary influence on serum lipids and lipoproteins. J Lipid Res 31:1149–1172

    PubMed  CAS  Google Scholar 

  40. Hayhurst GP, Lee YH, Lambert G, Ward JM, Gonzalez FJ (2001) Hepatocyte nuclear factor 4α (nuclear receptor 2A1) is essential for maintenance of hepatic gene expression and lipid homeostasis. Mol Cell Biol 21:1393–1403

    PubMed  CAS  Google Scholar 

  41. Sladek FM (1994) In: Tronche F, Yaniv M (eds) Liver gene expression, VRG Landes, Austin

  42. Hertz R, Magenheim J, Berman I, Bar-Tana J (1998) Fatty acyl-CoA thioesters are ligands of hepatic nuclear factor-4α. Nature 392:512–516

    PubMed  CAS  Google Scholar 

  43. Rajas F, Gautier A, Bady I, Montano S, Mithieux G (2002) Polyunsaturated fatty acyl CoA suppress the glucose-6-phosphate promoter activity by modulating the DNA binding of hepatocyte nuclear factor 4α. J Biol Chem 277:15736–15744

    PubMed  CAS  Google Scholar 

  44. Hertz R, Sheena V, Kalderon B, Berman I, Bar-Tana J (2001) Suppression of hepatocyte nuclear factor-4α by acyl-CoA thioesters of hypolipidemic peroxisome proliferators. Biochem Pharmacol 61:1057–1062

    PubMed  CAS  Google Scholar 

  45. Hertz R, Ben-Haim M, Petrescu A, Kalderon B, Berman I, Eldad N, Schroeder F, Bar-Tana J (2003) Rescue of MODY-1 by agonist ligands of hepatocyte nuclear factor-4α. J Biol Chem 278:22578–22585

    PubMed  CAS  Google Scholar 

  46. McArthur MJ, Atshaves BP, Frolov A, Foxworth WD, Kier AB, Schroeder F (1999) Cellular uptake and intracellular trafficking of long chain fatty acids. J Lipid Res 40:1371–1383

    PubMed  CAS  Google Scholar 

  47. Burrier RE, Manson CR, Brecher P (1987) Binding of acyl-CoA to liver fatty acid binding protein: effect on acyl-CoA synthesis. Biochim Biophys Acta 919:221–230

    PubMed  CAS  Google Scholar 

  48. Faergeman NJ, Knudsen J (1997) Role of long-chain fatty acyl-CoA esters in the regulation of metabolism and in cell signaling. Biochem J 323:1–12

    PubMed  CAS  Google Scholar 

  49. Knudsen J, Jensen MV, Hansen JK, Faergeman NJ, Neergard T, Gaigg B (1999) Role of acyl CoA binding protein in acyl CoA transport, metabolism, and cell signaling. Mol Cell Biochem 192:95–103

    PubMed  CAS  Google Scholar 

  50. Song M, Rebel G (1987) Rat liver nuclear lipids. Composition and biosynthesis. Bas Appl Histochem 31:377–387

    CAS  Google Scholar 

  51. Bucki R, Zendzian-Piotrowska M, Nawrocki A, Gorski J (1997) Effect of increased uptake of plasma fatty acids by the liver on lipid metabolism in the hepatocellular nuclei. Prost Leukot Essen Fatty Acids 57:27–31

    CAS  Google Scholar 

  52. Ves-Losada A, Mate SM, Brenner RR (2001) Incorporation and distribution of saturated and unsaturated fatty acids into nuclear lipids of hepatic cells. Lipids 36:273–282

    PubMed  CAS  Google Scholar 

  53. Ves-Losada A, Brenner RR (1996) Long-chain fatty acyl-CoA synthetase enzymatic activity in rat liver cell nuclei. Mol Cell Biochem 159:1–6

    PubMed  CAS  Google Scholar 

  54. Losada AV, Brenner RR (1998) Incorporation of delta-5 desaturase substrate (dihomogammalnolenic acid, 20:3 n-6) and product (arachidonic acid 20:4 n-6) into rat liver cell nuclei. Prost Leukot Essen Fatty Acids 59:39–47

    CAS  Google Scholar 

  55. Huang H, Starodub O, McIntosh A, Kier AB, Schroeder F (2002) Liver fatty acid binding protein targets fatty acids to the nucleus: real-time confocal and multiphoton fluorescence imaging in living cells. J Biol Chem 277:29139–29151

    PubMed  CAS  Google Scholar 

  56. Huang H, Starodub O, McIntosh A, Atshaves BP, Woldegiorgis G, Kier AB, Schroeder F (2004) Liver fatty acid binding protein colocalizes with peroxisome proliferator receptor alpha and enhances ligand distribution to nuclei of living cells. Biochemistry 43:2484–2500

    PubMed  CAS  Google Scholar 

  57. McIntosh A, Atshaves BP, Huang H, Payne HR, Hostetler HA, Davis J, Kier AB, Schroeder F (2007) Liver fatty acid binding protein gene ablation reduces nuclear targeting of fatty acid and fatty acyl-CoA in cultured mouse primary hepatocytes. Biochem J (submitted)

  58. Gossett RE, Edmondson RD, Jolly CA, Cho TH, Russell DH, Knudsen J, Kier AB, Schroeder F (1998) Structure and function of normal and transformed murine acyl-CoA binding proteins. Arch Biochem Biophys 350:201–213

    PubMed  CAS  Google Scholar 

  59. Frolov A, Cho TH, Murphy EJ, Schroeder F (1997) Isoforms of rat liver fatty acid binding protein differ in structure and affinity for fatty acids and fatty acyl-CoAs. Biochemistry 36:6545–6555

    PubMed  CAS  Google Scholar 

  60. Wolfrum C, Borchers T, Sacchettini JC, Spener F (2000) Binding of fatty acids and peroxisome proliferators to orthologous fatty acid binding proteins from human, murine, and bovine liver. Biochemistry 39:1469–1474

    PubMed  CAS  Google Scholar 

  61. Murakami K, Ide T, Nakazawa T, Okazaki T, Mochizuki T, Kadowaki T (2001) Fatty-acyl-CoA thioesters inhibit recruitment of steroid receptor co-activator 1 to α and γ isoforms of peroxisome-proliferator-activated receptors by competing with agonists. Biochem J 353:231–238

    PubMed  CAS  Google Scholar 

  62. Elholm M, Dam I, Jorgenesen C, Krogsdam AM, Holst D, Kratchamarova I, Gottlicher M, Gustafsson JA, Berge RK, Flatmark T, Knudsen J, Mandrup S, Kristiansen K (2001) Acyl-CoA esters antagonize the effects of ligands on peroxisome proliferator-activated receptor α conformation, DNA binding, and interaction with cofactors. J Biol Chem 276:21410–21416

    PubMed  CAS  Google Scholar 

  63. Bogan AA, Dallas-Yang Q, Ruse MD, Maeda Y, Jiang G, Nepomuceno L, Scanlan TS, Cohen FE, Sladek FM (2000) Analysis of protein dimerization and ligand binding of orphan receptor HNF4α. J Mol Biol 302:831–851

    PubMed  CAS  Google Scholar 

  64. Petrescu A, Huang H, Hertz R, Bar-Tana J, Schroeder F, Kier AB (2005) Role of regulatory F-domain in hepatocyte nuclear factor-4α ligand specificity. J Biol Chem 280:16714–16727

    PubMed  CAS  Google Scholar 

  65. Schroeder F, Huang H, Hostetler HA, Petrescu AD, Hertz R, Bar-Tana J, Kier AB (2005) Stability of fatty acyl CoA thioester ligands of hepatocyte nuclear factor-4α and peroxisome proliferator-activated receptor-α. Lipids 40:559–568

    PubMed  CAS  Google Scholar 

  66. Hertz R, Kalderon B, Byk T, Berman I, Zátara G, Mayer R, Bar-Tana J (2005) Thioesterase activity and acyl-CoA/fatty acid cross talk of hepatocyte nuclear factor-4α. J Biol Chem 280:24451–24461

    PubMed  CAS  Google Scholar 

  67. Dhe-Paganon S, Duda K, Iwamoto M, Chi YI, Shoelson SE (2002) Crystal structure of the HNF4α ligand binding domain in complex with endogenous fatty acid ligand. J Biol Chem 277:37973–37976

    PubMed  CAS  Google Scholar 

  68. Wisely GB, Miller AB, Davis RG, Thornquest AD, Johnson R, Spitzer T, Sefler A, Shearer B, Moore JT, Miller AB, Willson TM, Williams SP (2002) Hepatocyte nuclear factor 4 is a transcription factor that constitutively binds fatty acids. Structure 10:1225–1234

    PubMed  CAS  Google Scholar 

  69. Paulussen RJA, Veerkamp JH (1990) Intracellular fatty acid-binding proteins characteristics and function. In: Hilderson HJ (ed) Subcellular biochemistry. Plenum Press, New York

    Google Scholar 

  70. Veerkamp JH, Maatman RG, Prinsen CF (1992) Fatty acid-binding proteins: structural and functional diversity. Biochem Soc Trans 20:801–805

    PubMed  CAS  Google Scholar 

  71. Bass NM (1988) The cellular fatty acid binding proteins: aspects of structure, regulation, and function. Int Rev Cytol 111:143–184

    PubMed  CAS  Google Scholar 

  72. Banaszak L, Winter N, Xu Z, Bernlohr DA, Cowan S, Jones TA (1994) Lipid-binding proteins: a family of fatty acid and retinoid transport proteins. Adv Protein Chem 45:89–151

    PubMed  CAS  Google Scholar 

  73. Matarese V, Stone RL, Waggoner DW, Bernlohr DA (1989) Intracellular fatty acid trafficking and the role of cytosolic lipid binding proteins. Prog Lipid Res 28:245–272

    PubMed  CAS  Google Scholar 

  74. Borchers T, Spener F (1994) Fatty acid binding proteins. In: Hoekstra D (ed) Current topics in membranes, Academic, Orlando

    Google Scholar 

  75. Haunerland NH, Spener F (2004) Fatty acid binding proteins—insights from genetic manipulations. Prog Lipid Res 43:328–349

    PubMed  CAS  Google Scholar 

  76. Seedorf U, Raabe M, Ellinghaus P, Kannenberg F, Fobker M, Engel T, Denis S, Wouters F, Wirtz KWA, Wanders RJA, Maeda N, Assmann G (1998) Defective peroxisomal catabolism of branched fatty acyl coenzyme A in mice lacking the sterol carrier protein-2/sterol carrier protein-x gene function. Genes Dev 12:1189–1201

    PubMed  CAS  Google Scholar 

  77. Knudsen J, Faergeman NJ, Skott H, Hummel R, Borsting C, Rose TM, Andersen JS, Hojrup P, Roepstorff P, Kristiansen K (1994) Yeast acyl-CoA-binding protein: acyl-CoA-binding affinity and effect on intracellular acyl-CoA pool size. Biochem J 302:479–485

    PubMed  CAS  Google Scholar 

  78. Faergeman NJ, Wadum MCT, Feddersen S, Burton BB, Knudsen J (2007) Acyl-CoA binding proteins: structural and functional conservation over 2000 MYA. Mol Cell Biochem (in press)

  79. Schroeder F, Jolly CA, Cho TH, Frolov AA (1998) Fatty acid binding protein isoforms: structure and function. Chem Phys Lipids 92:1–25

    PubMed  CAS  Google Scholar 

  80. Frolov AA, Schroeder F (1998) Acyl coenzyme A binding protein: conformational sensitivity to long chain fatty acyl-CoA. J Biol Chem 273:11049–11055

    PubMed  CAS  Google Scholar 

  81. Huang H, Atshaves BP, Frolov A, Kier AB, Schroeder F (2005) Acyl-coenzyme A binding protein expression alters liver fatty acyl coenzyme A metabolism. Biochemistry 44:10282–10297

    PubMed  CAS  Google Scholar 

  82. Faergeman NJ, Sigurskjold BW, Kragelund BB, Andersen KV, Knudsen J (1996) Thermodynamics of ligand binding to acyl-coenzyme A binding protein studied by titration calorimetry. Biochemistry 35:14118–14126

    PubMed  CAS  Google Scholar 

  83. Rolf B, Oudenampsen-Kruger E, Borchers T, Faergeman NJ, Knudsen J, Lezius A, Spener F (1995) Analysis of the ligand binding properties of recombinant bovine liver-type fatty acid binding protein. Biochim Biophys Acta 1259:245–253

    PubMed  Google Scholar 

  84. Chao H, Zhou M, McIntosh A, Schroeder F, Kier AB (2003) Acyl-CoA binding protein and cholesterol differentially alter fatty acyl CoA utilization by microsomal acyl CoA: cholesterol transferase. J Lipid Res 44:72–83

    PubMed  CAS  Google Scholar 

  85. Bordewick U, Heese M, Borchers T, Robenek H, Spener F (1989) Compartmentation of hepatic fatty-acid-binding protein in liver cells and its effect on microsomal phosphatidic acid biosynthesis. Biol Chem Hoppe-Seyler 370:229–238

    PubMed  CAS  Google Scholar 

  86. Martin GG, Huang H, Atshaves BP, Binas B, Schroeder F (2003) Ablation of the liver fatty acid binding protein gene decreases fatty acyl-CoA binding capacity and alters fatty acyl-CoA pool distribution in mouse liver. Biochemistry 42:11520–11532

    PubMed  CAS  Google Scholar 

  87. Jolly CA, Wilton DA, Schroeder F (2000) Microsomal fatty acyl-CoA transacylation and hydrolysis: fatty acyl-CoA species dependent modulation by liver fatty acyl-CoA binding proteins. Biochim Biophys Acta 1483:185–197

    PubMed  CAS  Google Scholar 

  88. Jolly CA, Hubbell T, Behnke WD, Schroeder F (1997) Fatty acid binding protein: stimulation of microsomal phosphatidic acid formation. Arch Biochem Biophys 341:112–121

    PubMed  CAS  Google Scholar 

  89. Jolly CA, Murphy EJ, Schroeder F (1998) Differential influence of rat liver fatty acid binding protein isoforms on phospholipid fatty acid composition: phosphatidic acid biosynthesis and phospholipid fatty acid remodeling. Biochim Biophys Acta 1390:258–268

    PubMed  CAS  Google Scholar 

  90. Wolfrum C, Buhlman C, Rolf B, Borchers T, Spener F (1999) Variation of liver fatty acid binding protein content in the human hepatoma cell line HepG2 by peroxisome proliferators and antisense RNA affects the rate of fatty acid uptake. Biochim Biophys Acta 1437:194–201

    PubMed  CAS  Google Scholar 

  91. Atshaves BP, McIntosh AL, Lyuksyutova OI, Zipfel WR, Webb WW, Schroeder F (2004) Liver fatty acid binding protein gene ablation inhibits branched-chain fatty acid metabolism in cultured primary hepatocytes. J Biol Chem 279:30954–30965

    PubMed  CAS  Google Scholar 

  92. Atshaves BP, Storey S, Huang H, Schroeder F (2004) Liver fatty acid binding protein expression enhances branched-chain fatty acid metabolism. Mol Cell Biochem 259:115–129

    PubMed  CAS  Google Scholar 

  93. Martin GG, Danneberg H, Kumar LS, Atshaves BP, Erol E, Bader M, Schroeder F, Binas B (2003) Decreased liver fatty acid binding capacity and altered liver lipid distribution in mice lacking the liver fatty acid-binding protein gene. J Biol Chem 278:21429–21438

    PubMed  CAS  Google Scholar 

  94. Glatz JF, Baerwaldt CC, Veerkamp JH, Kempen HJ (1984) Diurnal variation of cytosolic fatty acid-binding protein content and of palmitate oxidation in rat liver and heart. J Biol Chem 259:4295–4300

    PubMed  CAS  Google Scholar 

  95. Veerkamp JH, van Moerkerk HT (1986) Peroxisomal fatty acid oxidation in rat and human tissues. Effect of nutritional state, clofibrate treatment and postnatal development in the rat. Biochim Biophys Acta 875:301–310

    PubMed  CAS  Google Scholar 

  96. Veerkamp JH (1995) Fatty acid transport and fatty acid-binding proteins. Proc Nutr Soc 54:23–37

    PubMed  CAS  Google Scholar 

  97. Veerkamp JH, van Moerkerk HT (1993) Fatty acid-binding protein and its relation to fatty acid oxidation. Mol Cell Biochem 123:101–106

    PubMed  CAS  Google Scholar 

  98. Pande SV (1973) Reversal by CoA of palmityl-CoA inhibition of long chain acyl-CoA synthetase activity. Biochim Biophys Acta 306:15–20

    PubMed  CAS  Google Scholar 

  99. Woldegiorgis G, Bremer J, Shrago E (1985) Substrate inhibition of carnitine palmitoyltransferase by palmitoyl-CoA and activation by phospholipids and proteins. Biochim Biophys Acta 837:135–140

    PubMed  CAS  Google Scholar 

  100. Martin GG, Atshaves BP, McIntosh AL, Kier AB, Schroeder F (2007) Effect of gender and age-dependent obesity on lipid metabolism in liver fatty acid binding protein (L-FABP) gene ablated mice. J Nutr (submitted)

  101. Erol E, Kumar LS, Cline GW, Shulman GI, Kelly DP, Binas B (2004) Liver fatty acid-binding protein is required for high rates of hepatic fatty acid oxidation but not for the action of PPAR-α in fasting mice. FASEB J 18:347–349

    PubMed  CAS  Google Scholar 

  102. Newberry EP, Xie Y, Kennedy S, Buhman KK, Luo J, Gross RW, Davidson NO (2003) Decreased hepatic triglyceride accumulation and altered fatty acid uptake in mice with deletion of the liver fatty acid binding protein gene. J Biol Chem 278:51664–51672

    PubMed  CAS  Google Scholar 

  103. Jolly CA, Hubbell T, Behnke WD, Schroeder F (1997) Fatty acid binding protein: stimulation of microsomal phosphatidic acid formation. Arch Biochem Biophys 341:112–121

    PubMed  CAS  Google Scholar 

  104. Murphy EJ, Schroeder F (1997) Sterol carrier protein-2 mediated cholesterol esterification in transfected L-cell fibroblasts. Biochim Biophys Acta 1345:283–292

    PubMed  CAS  Google Scholar 

  105. Mandrup S, Jepsen R, Skott H, Rosendal J, Hojrup P, Kristiansen K, Knudsen J (1993) Effect of heterologous expression of acyl-CoA-binding protein on acyl-CoA level and composition in yeast. Biochem J 290:369–374

    PubMed  CAS  Google Scholar 

  106. Bhuiyan AKMJ, Pande SV (1994) Carnitine palmitoyltransferase activities: effects of serum albumin, acyl-CoA binding protein and fatty acid binding protein. Mol Cell Biochem 139:109–116

    PubMed  CAS  Google Scholar 

  107. Bhuiyan AKMJ, Pande SV (1994) Carnitine palmitoyltransferase activies: effects of serum albumin, ACBP, and FABP. Mol Cell Biochem 139:109–116

    PubMed  CAS  Google Scholar 

  108. Luxon BA, Weisiger RA (1993) Sex differences in intracellular fatty acid transport: role of cytoplasmic binding proteins. Am J Physiol 265:G831–G841

    PubMed  CAS  Google Scholar 

  109. Weisiger RA (1996) Cytoplasmic transport of lipids: role of binding proteins. Comp Biochem Physiol 115B:319–331

    CAS  Google Scholar 

  110. Phelps-Luby K, Weisiger RA (1996) Role of cytoarchitecture in cytoplasmic transport. Comp Biochem Physiol 115B:295–306

    Google Scholar 

  111. Weisiger RA (2005) Cytosolic fatty acid binding proteins catalyze two distinct steps in intracellular transport of their ligands. Mol Cell Biochem 239:35–42

    Google Scholar 

  112. Murphy EJ (1998) L-FABP and I-FABP expression increase NBD-stearate uptake and cytoplasmic diffusion in L-cells. Am J Physiol 275:G244–G249

    PubMed  CAS  Google Scholar 

  113. Lawrence JW, Kroll DJ, Eacho PI (2000) Ligand dependent interaction of hepatic fatty acid binding protein with the nucleus. J Lipid Res 41:1390–1401

    PubMed  CAS  Google Scholar 

  114. Schroeder F, Atshaves BP, Starodub O, Boedeker AL, Smith R, Roths JB, Foxworth WB, Kier AB (2001) Expression of liver fatty acid binding protein alters growth and differentiation of embryonic stem cells. Mol Cell Biochem 219:127–138

    PubMed  CAS  Google Scholar 

  115. Borchers T, Unterberg C, Rudel H, Robenek H, Spener F (1989) Subcellular distribution of cardiac fatty acid-binding protein in bovine heart muscle and quantitation with an enzyme-linked immunosorbent assay. Biochim Biophys Acta 1002:54–61

    PubMed  CAS  Google Scholar 

  116. Tan NS, Shaw NS, Vinckenbosch N, Liu P, Yasmin R, Desvergne B, Wahli W, Noy N (2002) Selective cooperation between fatty acid binding proteins and peroxisome proliferatoractivated receptors in regulating transcription. Mol Cell Biol 22:5114–5127

    PubMed  CAS  Google Scholar 

  117. Hellendie T, Antonius M, Sorensen RV, Hertzel AV, Bernlohr DA, Kolvraa S, Kristiansen K, Mandrup S (2000) Lipid binding proteins modulate ligand-dependent trans-activation by peroxisome proliferator-activated receptors and localize to the nucleus as well as the cytoplasm. J Lipid Res 41:1740–1751

    Google Scholar 

  118. Budhu AS, Noy N (2002) Direct channeling of retinoic acid between cellular retinoic acid binding protein II and retinoic acid receptor sensitizes mammary carcinoma cells to retinoic acid induced growth arrest. Mol Cell Biol 22:2632–2641

    PubMed  CAS  Google Scholar 

  119. Delva L, Bastie JN, Rochette-Egly C, Kraiba R, Balitrand N, Despouy G, Chambon P, Chomienne C (1999) Physical and functional interactions between cellular retinoic acid binding protein II and the retinoic acid-dependent nuclear complex. Mol Cell Biol 19:7158–7167

    PubMed  CAS  Google Scholar 

  120. Petrescu AD, Payne HR, Boedeker AL, Chao H, Hertz R, Bar-Tana J, Schroeder F, Kier AB (2003) Physical and functional interaction of acyl-CoA-binding protein with hepatocyte nuclear factor-4α. J Biol Chem 278:51813–51824

    PubMed  CAS  Google Scholar 

  121. Elholm M, Garras A, Neve S, Tarnehave D, Lund TB, Skorve J, Flatmark T, Kristiansen K, Berge RK (2000) Long chain acyl-CoA esters and acyl-CoA binding protein are present in the nucleus of rat liver cells. J Lipid Res 41:538–545

    PubMed  CAS  Google Scholar 

  122. Petrescu AD, Vespa A, McIntosh AL, Schroeder F, Kier AB (2007) Structural and functional characterization of a new recombinant histidine-tagged acyl-CoA binding protein (ACBP) from mouse. Biochemistry (submitted)

  123. Bandichhor R, Petrescu AD, Vespa A, Kier AB, Schroeder F, Burgess K (2006) Synthesis of a new water soluble rhodamine derivative and application to intracellular imaging. J Am Chem Soc 128:10688–10689

    PubMed  CAS  Google Scholar 

  124. Dong D, Ruuska SE, Levinthal DJ, Noy N (1999) Distinct roles for cellular retinoic acid binding proteins I and II in regulating signaling by retinoic acid. J Biol Chem 274:23695–23698

    PubMed  CAS  Google Scholar 

  125. Nakahara M, Furuya N, Takagaki K, Sugaya T, Hirota K, Fukamizu A, Kanda T, Fujii H, Sato R (2005) Ileal bile acid binding protein, functionally associated with the farnesoid X receptor or the ileal bile acid transporter, regulates bile acid activity in the small intestine. J Biol Chem 280:42283–42289

    PubMed  CAS  Google Scholar 

  126. Wolfrum C, Ellinghaus P, Fobker M, Seedorf U, Assmann G, Borchers T, Spener F (1999) Phytanic acid is ligand and transcriptional activator of murine liver fatty acid binding protein. J Lipid Res 40:708–714

    PubMed  CAS  Google Scholar 

  127. Ockner RK, Manning JA (1976) Fatty acid binding protein. Role in esterification of absorbed long chain fatty acid in rat intestine. J Clin Inv 58:632–641

    Article  CAS  Google Scholar 

  128. ul-Haq R, Shrago E, Christodoulides L, Ketterer B (1985) Purification and characterization of fatty acid binding protein in mammalian lung. Exp Lung Res 9:43–55

    Google Scholar 

  129. McCormack M, Brecher P (1987) Effect of liver fatty acid binding protein on fatty acid movement between liposomes and rat liver microsomes. Biochem J 244:717–723

    PubMed  CAS  Google Scholar 

  130. Li Q, Yamamoto N, Morisawa S, Inoue A (1993) Fatty acyl-CoA binding activity of the nuclear thyroid hormone receptor. J Cell Biochem 51:458–464

    PubMed  CAS  Google Scholar 

  131. Kliewer SA, Umesono K, Noon DJ, Heyman RA, Evans RM (1992) Convergence of 9-cisretinoic acid and peroxisome proliferator signaling pathways through heterodimer formation of their receptors. Nature 358:771–774

    PubMed  CAS  Google Scholar 

  132. Perissi V, Rosenfeld MG (2005) Controlling nuclear receptors: the circular logic of cofactor cycles. Mol Cell Biol 6:542–554

    CAS  Google Scholar 

  133. Yamamoto T, Shimano H, Nakagawa Y, Ide T, Yahagi N, Matsuzuka T, Nakakuki M, Takahashi A, Suzuki H, Sone H, Toyoshima H, Sato R, Yamada N (2004) SREBP-1 interacts with hepatocyte nuclear factor-4α and interferes with PGC-1 recruitment to suppress hepatic gluconeogenic genes. J Bio Chem 279:12027–12035

    CAS  Google Scholar 

  134. Hashimoto T, Fujita T, Usuda N, Cook W, Qi C, Peters JM, Gonzalez FJ, Yeldandi AV, Rao MS, Reddy JK (1999) Peroxisomal and mitochondrial fatty acid β-oxidation in mice nullizygous for both PPARα and peroxisomal fatty acyl-CoA oxidase. J Biol Chem 274:19228–19236

    PubMed  CAS  Google Scholar 

  135. Lee SST, Pineau T, Drago J, Lee EJ, Owens JW, Kroetz DL, Fernandez-Salguero PM, Wesphal H, Gonzalez FJ (1995) Targeted disruption of the alpha isoform of the peroxisome proliferator-activated receptor gene in mice results in abolishment of the pleiotrophic effects of peroxisome proliferators. Mol Cell Biol 15:3012–3022

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported in part by the USPHS, National Institutes of Health grants DK41402 (FS and ABK), NIH P20 GM72041 (Project 2, ABK and FS) and DK70965 (BPA).

Author information

Authors and Affiliations

  1. Department of Physiology and Pharmacology, Texas A&M University, TVMC, College Station, TX, 77843-4466, USA

    Friedhelm Schroeder, Anca D. Petrescu, Huan Huang, Barbara P. Atshaves, Avery L. McIntosh, Gregory G. Martin, Heather A. Hostetler & Aude Vespa

  2. Department of Pathobiology, Texas A&M University, TVMC, College Station, TX, 77843-4467, USA

    Danilo Landrock, Kerstin K. Landrock, H. Ross Payne & Ann B. Kier

Authors
  1. Friedhelm Schroeder
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anca D. Petrescu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Huan Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Barbara P. Atshaves
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Avery L. McIntosh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Gregory G. Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Heather A. Hostetler
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Aude Vespa
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Danilo Landrock
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Kerstin K. Landrock
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. H. Ross Payne
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Ann B. Kier
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Friedhelm Schroeder.

About this article

Cite this article

Schroeder, F., Petrescu, A.D., Huang, H. et al. Role of Fatty Acid Binding Proteins and Long Chain Fatty Acids in Modulating Nuclear Receptors and Gene Transcription. Lipids 43, 1–17 (2008). https://doi.org/10.1007/s11745-007-3111-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11745-007-3111-z

Keywords

Search

Navigation