The Dipeptide H-Trp-Arg-OH (WR) Is a PPARα Agonist and Reduces Hepatic Lipid Accumulation in Lipid-Loaded H4IIE Cells

Yaoyao Jia, Jong Ho Kim, Bora Nam, Jiyoung Kim, Ji Hae Lee, Kyung Ok Kim, Kwang Yeon Hwang, Sung-Joon Lee

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Dipeptides absorbed by the intestinal epithelium are delivered to circulation, but their metabolic roles are not yet clearly understood. We investigated the biological activities of a dietary dipeptide, H-Trp-Arg-OH (WR), on the regulation of peroxisome proliferator-activated receptor (PPAR) α activity. Reporter gene assays revealed that WR dose-dependently induced PPARα transactivation. Surface plasmon resonance experiments demonstrated that WR interacts directly with the PPARα ligand binding domain, and time-resolved fluorescence energy transfer analyses revealed recruitment of a co-activator peptide, fluorescein-PGC1α, to PPARα, confirming the direct binding of WR to PPARα and occurrence of conformational changes. WR induced cellular fatty acid uptake and the expression of PPARα response genes in fatty acid oxidation, thus reducing intracellular triglyceride accumulation in lipid-loaded hepatocytes. In conclusion, the dietary dipeptide WR activates PPARα and reduces hepatic lipid accumulation in lipid-loaded hepatocytes.

Original languageEnglish
Pages (from-to)1211-1220
Number of pages10
JournalApplied Biochemistry and Biotechnology
Volume175
Issue number2
DOIs
Publication statusPublished - 2014 Jan 1

Keywords

  • Dipeptide
  • H-Trp-Arg-OH (WR)
  • Lipid metabolism
  • PPARα

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Biology

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