The dipeptide H-Trp-Glu-OH (WE) shows agonistic activity to peroxisome proliferator-activated protein-α and reduces hepatic lipid accumulation in lipid-loaded H4IIE cells

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

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Dipeptides digested from dietary proteins can be directly absorbed by the intestine and delivered to the circulatory system. However, the dipeptides' metabolic roles and biological activities are largely unknown. Lipid-loaded HII4E cells stimulated with H-Trp-Glu-OH (WE) exhibited reduced lipid accumulation, of which the effect was abolished by peroxisome proliferator-activated receptor (PPAR) α gene knock down. A luciferase assay showed that the WE dipeptide induced PPARα transactivation in a dose-dependent manner. Surface plasmon resonance and time-resolved fluorescence resonance energy transfer analyses demonstrated that WE interacts directly with the PPARα ligand binding domain (KD, 120 μM; EC 50, 83 μM). Cells stimulated with WE induced PPARα and its responsive genes and increased cellular fatty acid uptake. In conclusion, WE reduces hepatic lipid accumulation in lipid-loaded hepatocytes via the activation of PPARα by a direct interaction.

Original languageEnglish
Pages (from-to)2957-2962
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume24
Issue number13
DOIs
Publication statusPublished - 2014 Jul 1

Keywords

  • Dipeptide
  • H-Trp-Glu-OH (WE)
  • Lipid metabolism
  • Liver
  • PPARα

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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