ANGPTL4 is produced by entero-endocrine cells in the human intestinal tract.

S. Alex, L. Lichtenstein, W. Dijk, R.P. Mensink, N.S. Tan, S. Kersten

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Gut hormones produced by entero-endocrine cells (EEC) located throughout the gastrointestinal tract play a major role in the regulation of glucose and energy homeostasis. Angiopoietin-like 4 (ANGPTL4, also referred to as fasting induced adipose factor) is a secreted factor involved in regulation of lipid homeostasis and has been proposed as circulating mediator between the gut microbiota and fat storage in adipose tissue, although discordant data exist. Currently, little is known about the site and regulation of ANGPTL4 production in the intestine. Here, we show using immunohistochemistry and immunofluorescence that cells positive for ANGPTL4 are scattered along the epithelial layer in the human small and large intestine. ANGPTL4-positive cells exhibit typical features of EEC characterized by large ANGPTL4-positive secretory granules directed towards the basolateral side. In support, extensive overlap was observed between ANGPTL4-positive cells and cells positive for the entero-endocrine marker chromogranin A. Higher resolution images revealed that ANGPTL4 and chromogranin A are partially present in distinct intracellular vesicles. Using entero-endocrine HuTu-80 cells, ANGPTL4 secretion was shown to be induced by short chain fatty acids and reduced by bile acids. Finally, levels of ANGPTL4 in human plasma were significantly decreased following meal consumption. In conclusion, ANGPTL4 is produced by EEC in human intestine and expression may be regulated by short chain fatty acids and bile acids.
Original languageEnglish
Pages (from-to)383-391
Number of pages9
JournalHistochemistry and Cell Biology
Volume141
Issue number4
DOIs
Publication statusPublished - Apr 2014

Keywords

  • ANGPTL4
  • Entero-endocrine cells
  • Human intestine
  • Short chain fatty acids
  • ANGIOPOIETIN-LIKE PROTEIN-4
  • ACTIVATED RECEPTOR-GAMMA
  • DIET-INDUCED OBESITY
  • LIPOPROTEIN-LIPASE
  • CHROMOGRANIN-A
  • FATTY-ACIDS
  • ENTEROENDOCRINE CELLS
  • GUT MICROBIOTA
  • TARGET GENE
  • PLASMA

Cite this