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Gene Review

SLC27A6  -  solute carrier family 27 (fatty acid...

Homo sapiens

Synonyms: ACSVL2, FACVL2, FATP-6, FATP1, FATP6, ...
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Disease relevance of SLC27A6

  • The function of the FATP gene family is conserved throughout evolution as the C. elegans and mycobacterial FATPs facilitate LCFA uptake when overexpressed in COS cells or Escherichia coli, respectively [1].
  • FATP1 is an insulin-sensitive fatty acid transporter involved in diet-induced obesity [2].

High impact information on SLC27A6

  • New data reveal that insulin may regulate this process in part by promoting membrane trafficking of intracellular fatty acid transporters FATP1 and FATP4 to the plasma membrane [3].
  • 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 [2].
  • The strong protection against diet-induced obesity and insulin desensitization observed in FATP1-null animals suggests FATP1 as a novel antidiabetic target [2].
  • 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 [2].
  • Similarly, FATP1 is expressed by the BAT-derived cell line HIB-1B upon differentiation, and both fatty acid uptake and FATP1 protein levels are rapidly elevated following isoproterenol stimulation [4].

Biological context of SLC27A6

  • Phylogenetic analysis of amino acid sequences confirmed that hVLCS-H1 and hVLCS-H2 were evolutionarily closer to VLCSs than FATPs [5].
  • Similar to other FATPs, transient and stable transfection of FATP6 into 293 cells enhanced uptake of LCFAs [6].
  • As a consequence, FATP1 knockout (KO) animals display smaller lipid droplets in BAT and fail to defend their core body temperature at 4 degrees C, despite elevated serum free fatty acid levels [4].
  • These findings propose FATP4 as a candidate gene for the insulin resistance syndrome and provide a structural basis for understanding FATP function in NEFA transport and metabolism [7].
  • These results suggest that genetic variability in the FATP1 gene may affect lipid metabolism, especially in women, and reinforce the potential implication of FATP1 in lipid homeostasis [8].

Anatomical context of SLC27A6


Associations of SLC27A6 with chemical compounds

  • While one motif is also present in long-chain acyl-CoA synthetases, the other serves to distinguish the VLCS/FATP family from the long-chain synthetase family [5].
  • Stimulation of fatty uptake by isoproterenol required both protein kinase A and mitogen-activated kinase signaling and is completely dependent on FATP1 expression, as small-hairpin RNA-mediated knock down of FATP1 abrogated the effect [4].
  • We detected statistically significant associations between this FATP1 A/G polymorphism and an increase in plasma triglyceride levels, mainly in women [8].
  • The fatty acid transport proteins (FATP) and long-chain acyl coenzyme A synthetase (ACSL) proteins have been shown to play a role in facilitating long-chain fatty acid (LCFA) transport in mammalian cells under physiologic conditions [10].
  • Subsequent compaction of the flexible Nanogel network has resulted in an encapsulation of the FATP/PEI complex in a dense core surrounded by hydrophilic poly(ethylene glycol) (PEG) envelope [11].

Other interactions of SLC27A6

  • The other two (hVLCS-H1 and hVLCS-H2) were more closely related to rVLCS than to mFATP [5].
  • The amino acid sequence of hVLCS-H2 is 44-45% identical and 67-69% similar to those of both hVLCS and hVLCS-H1 [12].
  • In these membrane domains FATP6 also colocalizes with another molecule involved in LCFA uptake, CD36 [6].
  • The protein levels of the cardiac fatty acid transporters were reduced in the infarcted rat heart; FAT/CD36 by 36%, FABPpm by 12%, FATP6 by 21% and FATP1 by 26%, and the cytosolic fatty acid binding protein (cFABP) was 47% lower than in sham-operated rat hearts [13].

Analytical, diagnostic and therapeutic context of SLC27A6

  • FATP-1 mRNA expression was decreased in skeletal muscle in obese women both in nondiabetic and in type 2 diabetic patients (P < 0.02 vs. lean women in both groups), and in all women there was a negative correlation with basal FATP-1 mRNA level and body mass index (r = -0.74, P < 0.02) [9].


  1. A family of fatty acid transporters conserved from mycobacterium to man. Hirsch, D., Stahl, A., Lodish, H.F. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  2. FATP1 is an insulin-sensitive fatty acid transporter involved in diet-induced obesity. Wu, Q., Ortegon, A.M., Tsang, B., Doege, H., Feingold, K.R., Stahl, A. Mol. Cell. Biol. (2006) [Pubmed]
  3. Fat targets for insulin signaling. Czech, M.P. Mol. Cell (2002) [Pubmed]
  4. Fatty Acid transport protein 1 is required for nonshivering thermogenesis in brown adipose tissue. Wu, Q., Kazantzis, M., Doege, H., Ortegon, A.M., Tsang, B., Falcon, A., Stahl, A. Diabetes (2006) [Pubmed]
  5. Human very long-chain acyl-CoA synthetase and two human homologs: initial characterization and relationship to fatty acid transport protein. Watkins, P.A., Pevsner, J., Steinberg, S.J. Prostaglandins Leukot. Essent. Fatty Acids (1999) [Pubmed]
  6. Characterization of a heart-specific fatty acid transport protein. Gimeno, R.E., Ortegon, A.M., Patel, S., Punreddy, S., Ge, P., Sun, Y., Lodish, H.F., Stahl, A. J. Biol. Chem. (2003) [Pubmed]
  7. Genetic and structural evaluation of fatty acid transport protein-4 in relation to markers of the insulin resistance syndrome. Gertow, K., Bellanda, M., Eriksson, P., Boquist, S., Hamsten, A., Sunnerhagen, M., Fisher, R.M. J. Clin. Endocrinol. Metab. (2004) [Pubmed]
  8. Intronic polymorphism in the fatty acid transport protein 1 gene is associated with increased plasma triglyceride levels in a French population. Meirhaeghe, A., Martin, G., Nemoto, M., Deeb, S., Cottel, D., Auwerx, J., Amouyel, P., Helbecque, N. Arterioscler. Thromb. Vasc. Biol. (2000) [Pubmed]
  9. Fatty acid transport protein-1 mRNA expression in skeletal muscle and in adipose tissue in humans. Binnert, C., Koistinen, H.A., Martin, G., Andreelli, F., Ebeling, P., Koivisto, V.A., Laville, M., Auwerx, J., Vidal, H. Am. J. Physiol. Endocrinol. Metab. (2000) [Pubmed]
  10. Fatty acid transport protein 1 and long-chain acyl coenzyme A synthetase 1 interact in adipocytes. Richards, M.R., Harp, J.D., Ory, D.S., Schaffer, J.E. J. Lipid Res. (2006) [Pubmed]
  11. Polyplex Nanogel formulations for drug delivery of cytotoxic nucleoside analogs. Vinogradov, S.V., Zeman, A.D., Batrakova, E.V., Kabanov, A.V. Journal of controlled release : official journal of the Controlled Release Society. (2005) [Pubmed]
  12. Human liver-specific very-long-chain acyl-coenzyme A synthetase: cDNA cloning and characterization of a second enzymatically active protein. Steinberg, S.J., Wang, S.J., McGuinness, M.C., Watkins, P.A. Mol. Genet. Metab. (1999) [Pubmed]
  13. Fatty acid transporter levels and palmitate oxidation rate correlate with ejection fraction in the infarcted rat heart. Heather, L.C., Cole, M.A., Lygate, C.A., Evans, R.D., Stuckey, D.J., Murray, A.J., Neubauer, S., Clarke, K. Cardiovasc. Res. (2006) [Pubmed]
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