Role of fatty acid transport protein 4 in oleic acid-induced glucagon-like peptide-1 secretion from murine intestinal L cells

Am J Physiol Endocrinol Metab. 2012 Oct 1;303(7):E899-907. doi: 10.1152/ajpendo.00116.2012. Epub 2012 Aug 7.


The antidiabetic intestinal L cell hormone glucagon-like peptide-1 (GLP-1) enhances glucose-dependent insulin secretion and inhibits gastric emptying. GLP-1 secretion is stimulated by luminal oleic acid (OA), which crosses the cell membrane by an unknown mechanism. We hypothesized that L cell fatty acid transport proteins (FATPs) are essential for OA-induced GLP-1 release. Therefore, the murine GLUTag L cell model was used for immunoblotting, [(3)H]OA uptake assay, and GLP-1 secretion assay as determined by radioimmunoassay following treatment with OA ± phloretin, sulfo-N-succinimidyl oleate, or siRNA against FATP4. FATP4(-/-) and cluster-of-differentiation 36 (CD36)(-/-) mice received intraileal OA, and plasma GLP-1 was measured by sandwich immunoassay. GLUTag cells were found to express CD36, FATP1, FATP3, and FATP4. The cells demonstrated specific (3)H[OA] uptake that was dose-dependently inhibited by 500 and 1,000 μM unlabeled OA (P < 0.001). Cell viability was not altered by treatment with OA. Phloretin and sulfo-N-succinimidyl oleate, inhibitors of protein-mediated transport and CD36, respectively, also decreased [(3)H]OA uptake, as did knockdown of FATP4 by siRNA transfection (P < 0.05-0.001). OA dose-dependently increased GLP-1 secretion at 500 and 1,000 μM (P < 0.001), whereas phloretin, sulfo-N-succinimidyl oleate, and FATP4 knockdown decreased this response (P < 0.05-0.01). FATP4(-/-) mice displayed lower plasma GLP-1 at 60 min in response to intraileal OA (P < 0.05), whereas, unexpectedly, CD36(-/-) mice displayed higher basal GLP-1 levels (P < 0.01) but a normal response to intraileal OA. Together, these findings demonstrate a key role for FATP4 in OA-induced GLP-1 secretion from the murine L cell in vitro and in vivo, whereas the precise role of CD36 remains unclear.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD36 Antigens / analysis
  • CD36 Antigens / genetics
  • Cells, Cultured
  • Enteroendocrine Cells / drug effects
  • Enteroendocrine Cells / metabolism*
  • Fatty Acid Transport Proteins / analysis
  • Fatty Acid Transport Proteins / blood*
  • Fatty Acid Transport Proteins / genetics
  • Female
  • Gene Silencing
  • Glucagon-Like Peptide 1 / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oleic Acid / pharmacology*
  • Oleic Acids / pharmacology
  • Phloretin / pharmacology
  • Succinimides / pharmacology


  • CD36 Antigens
  • Fatty Acid Transport Proteins
  • Oleic Acids
  • Slc27a1 protein, mouse
  • Slc27a4 protein, mouse
  • Succinimides
  • sulfo-N-succinimidyl oleate
  • Oleic Acid
  • Glucagon-Like Peptide 1
  • Phloretin