NAPE-PLD controls OEA synthesis and fat absorption by regulating lipoprotein synthesis in an in vitro model of intestinal epithelial cells

Miki Igarashi, Kazuhide Watanabe, Tsuyoshi Tsuduki, Ikuo Kimura, Naoto Kubota

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Oleoylethanolamide (OEA), a fatty acid ethanolamide (FAE), is a lipid mediator that controls food intake and lipid metabolism. Accumulating data imply the importance of intestinal OEA in controlling satiety in addition to gastrointestinal peptide hormones. Although the biochemical pathway of FAE production has been illustrated, the enzymes responsible for the cleavage of OEA from its precursor N-acyl-phosphatidylethanolamine (NAPE) must be identified among reported candidates in the gut. In this study, we assessed the involvement of NAPE-specific phospholipase D (NAPE-PLD), which can directly release FAEs from NAPE, in intestinal OEA synthesis and lipid metabolism. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPER-associated protein 9 (Cas9)-mediated deletion of the NAPE-PLD gene in intestinal epithelial-like Caco-2 cells reduced OEA levels, regardless of their differentiation states. Transcriptome analysis revealed that deletion of NAPE-PLD activates a transcriptional program for nutrient transportation, including lipids and lipoproteins, and inactivates cell-cycle or mitosis-related genes in Caco-2 cells. In addition, the basolateral secretion of lipoproteins was increased in NAPE-PLD-deleted cells although lipoprotein size was not affected. By contrast, cellular lipid levels were reduced in NAPE-PLD-deleted cells. Overall, these results indicate that NAPE-PLD plays important roles in OEA synthesis and fat absorption by regulating lipoprotein production in the intestinal epithelial cells.—Igarashi, M., Watanabe, K., Tsuduki, T., Kimura, I., Kubota, N. NAPE-PLD controls OEA synthesis and fat absorption by regulating lipoprotein synthesis in an in vitro model of intestinal epithelial cells. FASEB J. 33, 3167–3179 (2019). www.fasebj.org.

Original languageEnglish
Pages (from-to)3167-3179
Number of pages13
JournalFASEB Journal
Volume33
Issue number3
DOIs
Publication statusPublished - 2019 Mar 1

Keywords

  • Caco-2
  • NAPE-PLD
  • fatty acid ethanolamide

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Fingerprint

Dive into the research topics of 'NAPE-PLD controls OEA synthesis and fat absorption by regulating lipoprotein synthesis in an in vitro model of intestinal epithelial cells'. Together they form a unique fingerprint.

Cite this