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

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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.

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Acknowledgments

We would like to thank Dries Mulder for providing humans intestinal samples. Current address for Laeticia Lichtenstein: Institut National de la Santé et de la Recherche Médicale (INSERM), Unit 563, Toulouse, France. The work was partially funded by a Grant from the EFSD/MSD European Research Programme on Novel Therapies for Type 2 Diabetes.

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Correspondence to Sander Kersten.

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Alex, S., Lichtenstein, L., Dijk, W. et al. ANGPTL4 is produced by entero-endocrine cells in the human intestinal tract. Histochem Cell Biol 141, 383–391 (2014). https://doi.org/10.1007/s00418-013-1157-y

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