This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wu, Q.
Right arrow Articles by Stahl, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wu, Q.
Right arrow Articles by Stahl, A.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, May 2006, p. 3455-3467, Vol. 26, No. 9
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.9.3455-3467.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

FATP1 Is an Insulin-Sensitive Fatty Acid Transporter Involved in Diet-Induced Obesity

Qiwei Wu,1 Angelica M. Ortegon,2 Bernice Tsang,2 Holger Doege,1 Kenneth R. Feingold,3 and Andreas Stahl1,2*

Palo Alto Medical Foundation Research Institute, 795 El Camino Real, Palo Alto, California 94301,2 Division of GI/Hepatology, Stanford University School of Medicine, Stanford, California 94305,1 Department of Veterans Affairs, 4150 Clement St., San Francisco, California 941213

Received 24 October 2005/ Returned for modification 22 November 2005/ Accepted 9 February 2006

Fatty acid transport protein 1 (FATP1), a member of the FATP/Slc27 protein family, enhances the cellular uptake of long-chain fatty acids (LCFAs) and is expressed in several insulin-sensitive tissues. In adipocytes and skeletal muscle, FATP1 translocates from an intracellular compartment to the plasma membrane in response to insulin. Here we show that insulin-stimulated fatty acid uptake is completely abolished in FATP1-null adipocytes and greatly reduced in skeletal muscle of FATP1-knockout animals while basal LCFA uptake by both tissues was unaffected. Moreover, loss of FATP1 function altered regulation of postprandial serum LCFA, causing a redistribution of lipids from adipocyte tissue and muscle to the liver, and led to a complete protection from diet-induced obesity and insulin desensitization. This is the first in vivo evidence that insulin can regulate the uptake of LCFA by tissues via FATP1 activation and that FATPs determine the tissue distribution of dietary lipids. The strong protection against diet-induced obesity and insulin desensitization observed in FATP1-null animals suggests FATP1 as a novel antidiabetic target.

* Corresponding author. Mailing address: Palo Alto Medical Foundation Research Institute, Ames Building, 795 El Camino Real, Palo Alto, CA 94301. Phone: (650) 614-3293. Fax: (650) 329-9114. E-mail: astahl{at}stanford.edu.

Molecular and Cellular Biology, May 2006, p. 3455-3467, Vol. 26, No. 9
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.9.3455-3467.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Lobo, S., Wiczer, B. M., Bernlohr, D. A. (2009). Functional Analysis of Long-chain Acyl-CoA Synthetase 1 in 3T3-L1 Adipocytes. J. Biol. Chem. 284: 18347-18356 [Abstract] [Full Text]  
  • Nickerson, J. G., Alkhateeb, H., Benton, C. R., Lally, J., Nickerson, J., Han, X.-X., Wilson, M. H., Jain, S. S., Snook, L. A., Glatz, J. F. C., Chabowski, A., Luiken, J. J. F. P., Bonen, A. (2009). Greater Transport Efficiencies of the Membrane Fatty Acid Transporters FAT/CD36 and FATP4 Compared with FABPpm and FATP1 and Differential Effects on Fatty Acid Esterification and Oxidation in Rat Skeletal Muscle. J. Biol. Chem. 284: 16522-16530 [Abstract] [Full Text]  
  • Holloway, G. P., Benton, C. R., Mullen, K. L., Yoshida, Y., Snook, L. A., Han, X.-X., Glatz, J. F. C., Luiken, J. J. F. P., Lally, J., Dyck, D. J., Bonen, A. (2009). In obese rat muscle transport of palmitate is increased and is channeled to triacylglycerol storage despite an increase in mitochondrial palmitate oxidation. Am. J. Physiol. Endocrinol. Metab. 296: E738-E747 [Abstract] [Full Text]  
  • Doege, H., Grimm, D., Falcon, A., Tsang, B., Storm, T. A., Xu, H., Ortegon, A. M., Kazantzis, M., Kay, M. A., Stahl, A. (2008). Silencing of Hepatic Fatty Acid Transporter Protein 5 in Vivo Reverses Diet-induced Non-alcoholic Fatty Liver Disease and Improves Hyperglycemia. J. Biol. Chem. 283: 22186-22192 [Abstract] [Full Text]  
  • Scapa, E. F., Pocai, A., Wu, M. K., Gutierrez-Juarez, R., Glenz, L., Kanno, K., Li, H., Biddinger, S., Jelicks, L. A., Rossetti, L., Cohen, D. E. (2008). Regulation of energy substrate utilization and hepatic insulin sensitivity by phosphatidylcholine transfer protein/StarD2. FASEB J. 22: 2579-2590 [Abstract] [Full Text]  
  • Watkins, P. A. (2008). Very-long-chain Acyl-CoA Synthetases. J. Biol. Chem. 283: 1773-1777 [Full Text]  
  • Li, H., Black, P. N., Chokshi, A., Sandoval-Alvarez, A., Vatsyayan, R., Sealls, W., DiRusso, C. C. (2008). High-throughput screening for fatty acid uptake inhibitors in humanized yeast identifies atypical antipsychotic drugs that cause dyslipidemias. J. Lipid Res. 49: 230-244 [Abstract] [Full Text]  
  • Hong, E.-G., Jung, D. Y., Ko, H. J., Zhang, Z., Ma, Z., Jun, J. Y., Kim, J. H., Sumner, A. D., Vary, T. C., Gardner, T. W., Bronson, S. K., Kim, J. K. (2007). Nonobese, insulin-deficient Ins2Akita mice develop type 2 diabetes phenotypes including insulin resistance and cardiac remodeling. Am. J. Physiol. Endocrinol. Metab. 293: E1687-E1696 [Abstract] [Full Text]  
  • Bonen, A., Han, X.-X., Habets, D. D. J., Febbraio, M., Glatz, J. F. C., Luiken, J. J. F. P. (2007). A null mutation in skeletal muscle FAT/CD36 reveals its essential role in insulin- and AICAR-stimulated fatty acid metabolism. Am. J. Physiol. Endocrinol. Metab. 292: E1740-E1749 [Abstract] [Full Text]  
  • Mattes, R. D. (2007). Effects of linoleic acid on sweet, sour, salty, and bitter taste thresholds and intensity ratings of adults. Am. J. Physiol. Gastrointest. Liver Physiol. 292: G1243-G1248 [Abstract] [Full Text]  
  • Lobo, S., Wiczer, B. M., Smith, A. J., Hall, A. M., Bernlohr, D. A. (2007). Fatty acid metabolism in adipocytes: functional analysis of fatty acid transport proteins 1 and 4. J. Lipid Res. 48: 609-620 [Abstract] [Full Text]  
  • Bonen, A., Chabowski, A., Luiken, J. J. F. P, Glatz, J. F. C. (2007). Mechanisms and Regulation of Protein-Mediated Cellular Fatty Acid Uptake: Molecular, Biochemical, and Physiological Evidence. Physiology 22: 15-28 [Full Text]  
  • Choi, S., Lee, M., Shiu, A. L., Yo, S. J., Aponte, G. W. (2007). Identification of a protein hydrolysate responsive G protein-coupled receptor in enterocytes. Am. J. Physiol. Gastrointest. Liver Physiol. 292: G98-G112 [Abstract] [Full Text]  
  • Wu, Q., Kazantzis, M., Doege, H., Ortegon, A. M., Tsang, B., Falcon, A., Stahl, A. (2006). Fatty Acid Transport Protein 1 Is Required for Nonshivering Thermogenesis in Brown Adipose Tissue. Diabetes 55: 3229-3237 [Abstract] [Full Text]  
  • Doege, H., Stahl, A. (2006). Protein-mediated Fatty Acid uptake: novel insights from in vivo models.. Physiology 21: 259-268 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»