Hostname: page-component-586b7cd67f-rdxmf Total loading time: 0 Render date: 2024-11-26T10:56:55.495Z Has data issue: false hasContentIssue false

New concepts of cellular fatty acid uptake: role of fatty acid transport proteins and of caveolae

Published online by Cambridge University Press:  05 March 2007

Jürgen Pohl
Affiliation:
Departments of Gastroenterology and Internal Medicine, University of Heidelberg, Bergheimer Str. 58, 69115, Heidelberg, Germany
Axel Ring
Affiliation:
Departments of Gastroenterology and Internal Medicine, University of Heidelberg, Bergheimer Str. 58, 69115, Heidelberg, Germany
Thomas Herrmann
Affiliation:
Departments of Gastroenterology and Internal Medicine, University of Heidelberg, Bergheimer Str. 58, 69115, Heidelberg, Germany
Wolfgang Stremmel*
Affiliation:
Departments of Gastroenterology and Internal Medicine, University of Heidelberg, Bergheimer Str. 58, 69115, Heidelberg, Germany
*
*Corresponding author: Professor Wolfgang Stremmel Fax: +49 62 21 56 41 16, Email: [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Efficient uptake and channelling of long-chain fatty acids (LCFA) are critical cell functions. Evidence is emerging that proteins are important mediators of LCFA-trafficking into cells and various proteins have been suggested to be involved in this process. Amongst these proteins is a family of membrane-associated proteins termed fatty acid transport proteins (FATP). So far six members of this family, designated FATP 1–6, have been characterized. FATP 1, 2 and 6 show a highly-conserved AMP-binding region that participates in the activation of very-long-chain fatty acids (VLCFA) to form their acyl-CoA derivatives. The mechanisms by which FATP mediate LCFA uptake are not well understood, but several studies provide evidence that uptake of LCFA across cellular membranes is closely linked to acyl-CoA synthetase activity. It is proposed that FATP indirectly enhance LCFA uptake by activating VLCFA to their CoA esters, which are required to maintain the typical structure of lipid rafts in cellular membranes. Recent work has shown that the structural integrity of lipid rafts is essential for cellular LCFA uptake. This effect might be exerted by proteins, e.g. caveolin-1 and FAT/CD36, that use lipid rafts as platforms and bind or transport LCFA. The proposed molecular mechanisms await further experimental investigation.

Type
The fatty acid transporters of skeletal muscle
Copyright
Copyright © The Nutrition Society 2004

References

Abumrad, NA, El-Maghrabi, MR, Amri, EZ, Lopez, E & Grimaldi, PA (1993) Cloning of rat adipocyte membrane-protein implicated in binding or transport of long chain fatty acids that is induced during preadipocyte differentiation: homology with human CD 36. Journal of Biological Chemistry 268, 1766517668.CrossRefGoogle ScholarPubMed
Berger, J, Truppe, C, Neumann, H, Forss-Petter, S (1998) A novel relative of the very-long-chain acyl-CoA synthetase and fatty acid transporter protein genes with a distinct expression pattern. Biochemical and Biophysical Research Communications 247, 255260.Google Scholar
Coe, NR, Smith, AJ, Frohnert, BI, Watkins, PA & Bernlohr, DA (1999) The fatty acid transport protein (FATP1) is a very long chain acyl-CoA synthetase. Journal of Biological Chemistry 274, 3630036304.Google Scholar
Frohnert, BI & Bernlohr, DA (2000) Regulation of fatty acid transporters in mammalian cells. Progress in Lipid Research 39, 83107.CrossRefGoogle ScholarPubMed
Gimeno, RE, Ortegon, AM, Patel, S, Punreddy, S, Ge, P, Sun, Y, Lodish, HF & Stahl, A (2003) Characterization of a heart-specific fatty acid transport protein. Journal of Biological Chemistry 278, 1603916044.Google Scholar
Herrmann, T, Buchkremer, F, Gosch, I, Hall, AM, Bernlohr, DA & Stremmel, W (2001) Mouse fatty acid transport protein 4 (FATP4): Characterization of the gene and functional assessment as a very long chain acyl-CoA synthetase. Gene 270, 3140.CrossRefGoogle ScholarPubMed
Herrmann, T van der Hoeven, F, Gröne, HJ, Stewart, AF, Langbein, L, Kaiser, I, Liebisch, G, Gosch, I, Buchkremer, F, Drobnik, W, Schmitz, G & Stremmel, W (2003) Mice with targeted disruption of the fatty acid transport protein 4 (Fatp 4, Slc27a4) gene show features of lethal restrictive dermopathy. Journal of Cell Biology 161, 11051115.CrossRefGoogle ScholarPubMed
Hirsch, D, Stahl, A & Lodish, HF (1998) A family of fatty acid transporters conserved from mycobacterium to man. Proceedings of the National Academy of Sciences USA 95, 86258629.Google Scholar
Kolleck, I, Guthmann, F, Ladhoff, AM, Tandon, NN, Schlame, M & Rüstow, B (2002) Cellular cholesterol stimulates uptake of palmitate by redistribution of fatty acid translocase in type II pneumocytes. Biochemistry 41, 63696375.Google Scholar
Lewis, SE, Listenberger, LL, Ory, DS & Schaffer, JE (2001) Membrane topology of the murine fatty acid transport protein 1. Journal of Biological Chemistry 276, 3704237050.Google Scholar
Pohl, J, Ring, A & Stremmel, W (2002) Uptake of long-chain fatty acids in HepG2 cells involves caveolae: analysis of a novel pathway. Journal of Lipid Research 43, 13901399.Google Scholar
Razani, B, Engelman, JA, Wang, XB, Schubert, W, Zhang, XL & Marks, CB, et al. (2001) Caveolin-1 null mice are viable but show evidence of hyperproliferative and vascular abnormalities. Journal of Biological Chemistry 276, 3812138138.Google Scholar
Razani, B, Combs, TP, Wang, XB, Frank, PG, Park, DS, Russell, RG, Li, M, Tang, B, Jelicks, LA, Scherer, PE & Lisanti, MP (2002) Caveolin-1 deficient mice are lean, resistant to diet-induced obesity, and show hypertriglyceridemia with adipocyte abnormalities. Journal of Biological Chemistry 277, 86358647.Google Scholar
Rietveld, A & Simons, K (1998) The differential miscibility of lipids as the basis for the formation of functional membrane rafts. Biochimica et Biophysica Acta 1376, 467479.Google Scholar
Ring, A, Pohl, J, Völkl, A & Stremmel, W (2002) Evidence for vesicles that mediate long-chain fatty acid uptake by human microvascular endothelial cells. Journal of Lipid Research 43, 2009520104.Google Scholar
Schaffer, JE & Lodish, HF (1994) Expression cloning and characterization of a novel adipocyte long chain fatty acid transport protein. Cell 79, 427436.Google Scholar
Simons, K & Ehehalt, R (2002) Cholesterol, lipid rafts, and disease. Journal of Clinical Investigation 110, 597603.Google Scholar
Sotgia, F, Razani, B, Bonuccelli, G, Schubert, W, Battista, M, Lee, H, Capozza, F, Schubert, AL, Minetti, C, Buckley, JT & Lisanti, MP (2002) Intracellular retention of glycosylphosphatidyl inositol-linked proteins in caveolin-deficient cells. Molecular and Cellular Biology 22, 39053926.Google Scholar
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. Developmental Cell 2, 477488.Google Scholar
Stahl, A, Gimeno, RE, Tartaglia, LA & Lodish, HF (2001) Fatty acid transport proteins: a current view of a growing family. Trends in Endocrinology and Metabolism 12, 266273.Google Scholar
Stahl, A, Hirsch, DJ, Gimeno, RE, Punreddy, S, Ge, P, Watson, N, Patel, S, Kotler, M, Raimondi, A, Tartaglia, LA & Lodish, HF (1999) Identification of the major intestinal fatty acid transport protein. Molecular Cell 3, 299308.CrossRefGoogle Scholar
Steinberg, SJ, Wang, SJ, Kim, DG, Mihalik, SJ & Watkins, PA, (1999a) Human very-long-chain acyl-CoA synthetase. Cloning, topography, and relevance to branched-chain fatty acid metabolism. Biochemical and Biophysical Research Communications 257, 615621.Google Scholar
Steinberg, SJ, Wang, SJ, McGuinness, MC & Watkins, PA (1999b) Human liver-specific very-long-chain acyl-coenzyme A synthetase: cDNA cloning and characterization of a second enzymatically active protein. Molecular Genetics and Metabolism 68, 3242.Google Scholar
Trigatti, BL, Anderson, RG & Gerber, GE (1999) Identification of caveolin-1 as a fatty acid binding protein. Biochemical and Biophysical Research Communications 255, 3439.Google Scholar