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Regulation of fatty acid transport: from transcriptional to posttranscriptional effects

  • Adrian ChabowskiEmail author
  • Jan Górski
  • Arend Bonen
Editorial

Long-chain fatty acids (LCFA) are essential for many cellular functions. In metabolically active tissues such as heart and skeletal muscle their principal role is to supply oxidative substrates. LCFA serve also as structural components of various lipids and proteins, and function in intracellular signaling. Although LCFA can enter into the cells via simple diffusion (Hamilton and Kamp 1999; Hamilton et al. 2002), LCFA utilization is not simply a function of blood LCFA levels, as plasmalemmal LCFA transport has been shown to be regulated at the tissue level (Turcotte et al. 1994; Coburn et al. 2000; Hajri et al. 2001). In particular, the membrane proteins such as FAT/CD36, FABPpm and FATP’s were shown to facilitate LCFA movement across the plasma membranes in skeletal muscle as well as in heart (Bonen et al. 2002; Schaffer 2002). Fatty-acid transporters are regulated proteins whose expression is modulated through transcriptional and post-transcriptional mechanisms. Recently, it was...

Keywords

Human Skeletal Muscle CD36 Deficiency Human Skeletal Muscle Cell Total Protein Expression LCFA Uptake 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Aas V, Rokling-Andersen MH, Kase ET, Thoresen GH, Rustan AC (2006) Eicosapentaenoic acid (20:5 n-3) increases fatty acid and glucose uptake in cultured human skeletal muscle cells. J Lipid Res 47:366–374CrossRefPubMedGoogle Scholar
  2. Abmurad NA (2005) CD36 may determine our desire for dietary fats. J Clin Invest 115:2965–2967CrossRefPubMedGoogle Scholar
  3. Abumrad NA, El-Maghrabi MR, Amri E-Z, Lopez E, Grimaldi P (1993) Cloning of a rat adipocyte membrane protein implicated in binding or transport of long chain fatty acids that is induced during preadipocyte differentiation. Homology with human CD36. J Biol Chem 268: 17665–17668PubMedGoogle Scholar
  4. Aitman TJ, Glazier AM, Wallace CA, Cooper LD, Norsworthy PJ, Wahid FN, Al-Majali KM, Trembling PM, Mann CJ, Shoulders CC, Garf D, St. Lezin E, Kurtz TW, Kren V, Pravenec M, Ibrahimi A, Abumrad NA, Stanton LW, Scott J (1999) Identification of Cd36 (Fat) as an insulin-resistance gene causing defective fatty acid and glucose metabolism in hypertensive rats. Nat Genet 21:76–83CrossRefPubMedGoogle Scholar
  5. Berk PD, Zhou S-L, Kiang C-L, Stump D, Bradbury M, Isola L (1997) Uptake of long chain fatty acids is selectively up-regulated in adipocytes of Zucker rats with genetic obesity and non-insulin-dependent diabetes mellitus. J Biol Chem 272:8830–8835CrossRefPubMedGoogle Scholar
  6. Berk PD, Zhou S-L, Kiang C-L, Stump D, Fan X, Bradbury M (1999) Selective upregulation of fatty acid uptake by adipocytes characterizes both genetic and diet-induced obesity in rodents. J Biol Chem 274:28626–28631CrossRefPubMedGoogle Scholar
  7. Bonen A, Luiken JJFP, Lui S, Dyck DJ, Kiens B, Kristiansen S, Turcotte L, van der Vusse GJ, Glatz JFC (1998) Palmitate transport and fatty acid transporters in red and white muscles. Am J Physiol Endocrinol Metab 275:E471–E478Google Scholar
  8. Bonen A, Dyck DJ, Ibrahimi A, Abumrad NA (1999) Muscle contractile activity increases fatty acid metabolism and transport and FAT/CD36. Am J Physiol Endocrinol Metab 276:E642–E649Google Scholar
  9. Bonen A, Luiken JJFP, Arumugam Y, Glatz JFC, Tandon NN (2000) Acute regulation of fatty acid uptake involves the cellular redistribution of fatty acid translocase. J Biol Chem 275:14501–14508CrossRefPubMedGoogle Scholar
  10. Bonen A, Glatz JF, Luiken JJFP (2002) Regulation of fatty acid transport and membrane transporters in health and disease. Mol Cell Biochem 239:181–192CrossRefPubMedGoogle Scholar
  11. Bonen A, Campbell SE, Benton CR, Chabowski A, Coort SL, Han XX, Koonen DP, Glatz JF, Luiken JJ (2004a) Regulation of fatty acid transport by fatty acid translocase/CD36. Proc Nutr Soc 63:245–249CrossRefPubMedGoogle Scholar
  12. Bonen A, Parolin ML, Steinberg GR, Calles-Escandon J, Tandon NN, Glatz JFC, Luiken JJFP, Heigenhauser GJF, Dyck DJ (2004b) Triacylglycerol Accumulation in Human Obesity and Type 2 diabetes is associated with increased rates of skeletal muscle fatty acid transportand increased sarcolemmal FAT/CD36. FASEB J 18:1144–1146PubMedGoogle Scholar
  13. Cameron-Smith D, Burke LM, Angus DJ, Tunstall RJ, Cox GR, Bonen A, Hawley JA, Hargreaves M (2003) A short-term, high-fat diet up-regulates lipid metabolism and gene expression in human skeletal muscle. Am J Clin Nutr 77:313–318PubMedGoogle Scholar
  14. Campbell SE, Tandon NN, Woldegiorgis G, Luiken JJFP, Glatz JFC, Bonen A (2004) A novel function for FAT/CD36: involvement in long chain fatty acid transfer into the mitochondria. J Biol Chem 279:36235–36241CrossRefPubMedGoogle Scholar
  15. Chabowski A, Coort SL, Calles-Escandon J, Tandon NN, Glatz JF, Luiken JJ, Bonen A (2004) Insulin stimulates fatty acid transport by regulating expression of FAT/CD36 but not FABPpm. Am J Physiol Endocrinol Metab 287:E781–E789PubMedCrossRefGoogle Scholar
  16. Chabowski A, Coort SL, Calles-Escandon J, Tandon NN, Glatz JF, Luiken JJ, Bonen A (2005) The subcellular compartmentation of fatty acid transporters is regulated differently by insulin and by AICAR. FEBS Lett 579:2428–2432CrossRefPubMedGoogle Scholar
  17. Chabowski A, Momken I, Coort SLM, Calles-Escandon J, Tandon NN, Glatz JFC, Luiken JJFP, Bonen (2006) A prolonged AMPK activation increases the expression of fatty acid transporters in cardiac myocytes and perfused hearts. Mol Cell Biochem (in press)Google Scholar
  18. Clarke DC, Miskovic D, Han X-X, Calles-Escandon J, Glatz JFC, Luiken JJFP, Heikkila JJ, Bonen A (2004) Overexpression of membrane associated fatty acid binding protein (FABPpm) in vivo increases fatty acid sarcolemmal transport and metabolism. Physiol Genomics 17:31–37CrossRefPubMedGoogle Scholar
  19. Coburn CT, Knapp FF Jr, Febbraio M, Beets AL, Silverstein RL, Abumrad NA (2000) Defective uptake and utilization of long chain fatty acids in muscle and adipose tissue of CD36 knockout mice. J Biol Chem 275:32523–32529CrossRefPubMedGoogle Scholar
  20. Fabris R, Nisoli E, Lombardi AM, Tonello C, Serra R, Granzotto M, Cusin I, Rohner-Jeanrenaud F, Federspil G, Carruba MO, Vettor R (2001) Preferential channeling of energy fuels toward fat rather than muscle during high free fatty acid availability in rats. Diabetes 50:601–608PubMedCrossRefGoogle Scholar
  21. Febbraio M, Abumrad NA, Hajjar DP, Sharma K, Cheng W, Frieda S, Pearce A, Silverstein RL (1999) A null mutation in murine CD36 reveals an important role in fatty acid and lipoprotein metabolism. J Biol Chem 274:19055–19062CrossRefPubMedGoogle Scholar
  22. Febbraio M, Guy E, Coburn C, Knapp FF Jr, Beets AL, Abumrad NA, Silverstein RL (2002) The impact of overexpression and deficiency of fatty acid translocase (FAT)/CD36. Mol Cell Biochem 239:193–197CrossRefPubMedGoogle Scholar
  23. Furuhashi M, Ura N, Nakata T, Shimamoto K (2003) Insulin sensitivity and lipid metabolism in human CD36 deficiency. Diabetes Care 26:471–474PubMedCrossRefGoogle Scholar
  24. Furuhashi M, Ura N, Nakata T, Tanaka T, Shimamoto K (2004) Genotype in human CD36 deficiency and diabetes mellitus. Diabet Med 21:952–953CrossRefPubMedGoogle Scholar
  25. Hajri T, Ibrahimi A, Coburn CT, Knapp FF Jr, Kurtz T, Pravenec M, Abumrad NA (2001) Defective fatty acid uptake in the spontaneously hypertensive rat is a primary determinant of altered glucose metabolism, hyperinsulinemia, and myocardial hypertrophy. J Biol Chem 276:23661–23666CrossRefPubMedGoogle Scholar
  26. Hamilton JA, Kamp F (1999) How are free fatty acids transported in membranes? Is it by proteins or by free diffusion through the lipids? Diabetes 48:2255–2269PubMedCrossRefGoogle Scholar
  27. Hamilton J, Guo W, Kamp F (2002) Mechanisms of cellular uptake of long-chain fatty acids: do we need cellulr proteins? Mol Cell Biochem 239: 17–23CrossRefPubMedGoogle Scholar
  28. Holloway GP, Bezaire V, Heigenhauser GJ, Tandon NN, Glatz JF, Luiken JJ, Bonen A, Spriet LL (2006) Mitochondrial long chain fatty acid oxidation, fatty acid translocase/CD36 content and carnitine palmitoyltransferase I activity in human skeletal muscle during aerobic exercise. J Physiol 571:201–210CrossRefPubMedGoogle Scholar
  29. Ibrahimi A, Bonen A, Blinn WD, Hajri T, Li X, Zhong K, Cameron R, Abumrad NA (1999) Muscle-specific overexpression of FAT/CD36 enhances fatty acid oxidation by contracting muscles, reduces plasma triglycerides and fatty acids, and increases plasma glucose and insulin. J Biol Chem 274:26761–26766CrossRefPubMedGoogle Scholar
  30. Kelley DA, Mandarino LJ (2000) Fuel selection in human skeletal muscle in insulin resistance. A reexamination. Diabetes 49:677–683PubMedCrossRefGoogle Scholar
  31. Kelley DE, Goodpaster B, Wing RR, Simoneau JA (1999) Skeletal muscle fatty acid metabolism in association with insulin resistance, obesity, and weight loss. Am J Physiol Endocrinol Metab 277:E1130–E1141Google Scholar
  32. Koonen DPY, Benton CR, Arumugam Y, Tandon NN, Calles-Escandon J, Glatz JFC, Luiken JJFP, Bonen A (2004) Different mechanism can alter fatty acid tansport when muscle contractile activity is chronically altered. Am J Physiol Endocrinol Metab 286:E1042–E1049CrossRefPubMedGoogle Scholar
  33. Koonen DP, Glatz JF, Bonen A, Luiken JJ (2005) Long-chain fatty acid uptake and FAT/CD36 translocation in heart and skeletal muscle. Biochim Biophys Acta 1736:163–180PubMedGoogle Scholar
  34. Lepretre F, Linton KJ, Lacquemant C, Vatin V, Samson C, Dina C, Chikri M, Ali S, Scherer P, Seron K, Vasseur F, Aitman T, Froguel P (2004) Genetic study of the CD36 gene in a French diabetic population. Diabetes Metab 30:459–463PubMedCrossRefGoogle Scholar
  35. Li Y-Q, Ji H, Zhang Y-H, Ding D-Y, Ye X-L (2006) Metabolic effects of telmisartan in spontaneously hypertnsive rats. Naunyn-Schmiedeberg’s Arch Pharmacol. DOI 10.1007/s00210-006-0069-y
  36. Luiken JJFP, Schaap FG, van Nieuwenhoven FA, van der Vusse GJ, Bonen A, Glatz JF (1999a) Cellular fatty acid transport in heart and skeletal muscle as facilitated by proteins. Lipids 34:S169–S175PubMedCrossRefGoogle Scholar
  37. Luiken JJFP, Turcotte LP, Bonen A (1999b) Protein-mediated palmitate uptake and expression of fatty acid transport proteins in heart giant vesicles. J Lipid Res 40:1007–1016PubMedGoogle Scholar
  38. Luiken JJFP, Arumugam Y, Dyck DJ, Bell RC, Pelsers ML, Turcotte LP, Tandon NN, Glatz JFC, Bonen A (2001) Increased rates of fatty acid uptake and plasmalemmal fatty acid transporters in obese Zucker rats. J Biol Chem 276:40567–40573CrossRefPubMedGoogle Scholar
  39. Luiken JJFP, Arumugam Y, Bell RC, Calles-Escandon J, Tandon NN, Glatz JFC, Bonen A (2002a) Changes in fatty acid transport and transporters are related to the severity of insulin deficiency. Am J Physiol Endocrinol Metab 282:612–621Google Scholar
  40. Luiken JJFP, Dyck DJ, Han X-X, Tandon NN, Arumugam Y, Glatz JFC, Bonen A (2002b) Insulin induces the translocation of the fatty acid transporter FAT/CD36 to the plasma membrane. Am J Physiol Endocrinol Metab 282:E491–E495PubMedGoogle Scholar
  41. Luiken JJFP, Koonen DPY, Willems J, Zorzano A, Fischer Y, van der Vusse GJ, Bonen A, Glatz JFC (2002c) Insulin stimulates long-chain fatty acid uilization by rat cardiac myocytes through cellular redistribution of FAT/CD36. Diabetes 51:3113–3119PubMedCrossRefGoogle Scholar
  42. Luiken JJFP, Coort SML, Willems J, Coumans WA, Bonen A, van der Vusse GJ, Glatz JFC (2003) Contraction-induced fatty acid translocase/CD36 translocation in rat cardiac myocytes is mediated through AMP-activated protein kinase signaling. Diabetes 52:1627–1634PubMedCrossRefGoogle Scholar
  43. Memon RA, Fuller J, Moser AH, Smith PJ, Grunfeld C, Feingold KR (1999) Regulation of putative fatty acid transporters and Acyl–CoA synthetase in liver and adipose tissue in ob/ob mice. Diabetes 48:121–127PubMedCrossRefGoogle Scholar
  44. Nisoli E, Carruba MO, Tonello C, Macor C, Federspil G, Vettor R (2000) Induction of fatty acid translocase/CD36, peroxisome proliferator-activated receptor-gamma2, leptin, uncoupling proteins 2 and 3, and tumor necrosis factor-alpha gene expression in human subcutaneous fat by lipid infusion. Diabetes 49:319–324PubMedCrossRefGoogle Scholar
  45. Palanivel R, Sweeney G (2005) Regulation of fatty acid uptake and metabolism in L6 skeletal muscle cells by resistin. FEBS Lett 579:5049–5054CrossRefPubMedGoogle Scholar
  46. Petersen KF, Dufour D, Befroy R, Garcia GI (2004) Impaired mitochondrial activity in the insulin resistant offspring of patients with type 2 diabetes. N Engl J Med 350:664–671CrossRefPubMedGoogle Scholar
  47. Schaffer JE (2002) Fatty acid transport: the roads taken. Am J Physiol Endocrinol Metab 282:E239–E246PubMedGoogle Scholar
  48. Schrauwen-Hinderling VB, Kooi ME, Hesselink MK, Moonen-Kornips E, Schaart G, Mustard KJ, Hardie DG, Saris WH, Nicolay K, Schrauwen P (2005) Intramyocellular lipid content and molecular adaptations in response to a 1-week high-fat diet. Obes Res 13:2088–2094PubMedCrossRefGoogle Scholar
  49. Stahl A, Evans JG, Pattel S, Hirsch D, Lodish HF (2002) Insulin causes fatty acid transport protein translocation and enhanced fatty acid uptake in adipocytes. Dev Cell 2:477–488CrossRefPubMedGoogle Scholar
  50. Steinberg GR, Dyck DJ, Calles-Escandon J, Tandon NN, Luiken JJFP, Glatz JF, Bonen A (2002) Chronic leptin administration decreases fatty acid uptake and fatty acid transporters in rat skeletal muscle. J Biol Chem 277:8854–8860CrossRefPubMedGoogle Scholar
  51. Tanaka T, Sohmiya K, Kawamura K (1997) Is CD36 deficiency an etiology of hereditary hypertrophic cardiomyopathy. J Mol Cell Cardiol 29:121–127CrossRefPubMedGoogle Scholar
  52. Tunstall RJ, Cameron-Smith D (2005) Effect of elevated lipid concentrations on human skeletal muscle gene expression. Metabolism 54:952–959CrossRefPubMedGoogle Scholar
  53. Tunstall RJ, Mehan KA, Hargreaves M, Spriet LL, Cameron-Smith D (2002) Fasting activates the gene expression of UCP3 independent of genes necessary for lipid transport and oxidation in skeletal muscle. Biochem Biophys Res Commun 294:301–308CrossRefPubMedGoogle Scholar
  54. Turcotte LP, Hespel PJ, Graham TE, Richter EA (1994) Impaired plasma FFA oxidation imposed by extreme CHO deficiency in contracting rat skeletal muscle. J Appl Physiol 77:517–525PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  1. 1.Department of PhysiologyMedical University of BialystokBialystokPoland
  2. 2.Department of Human Health and Nutritional SciencesUniversity of GuelphGuelphCanada

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