Format

Send to

Choose Destination
See comment in PubMed Commons below
Bioorg Med Chem Lett. 2014 Jul 1;24(13):2957-62. doi: 10.1016/j.bmcl.2014.04.019. Epub 2014 Apr 13.

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.

Author information

1
Department of Biotechnology, Graduate School of Biotechnology, Korea University, Seoul 136-713 Republic of Korea.
2
Department of Biosystems & Biotechnology, Graduate School of Biotechnology, Korea University, Seoul 136-713 Republic of Korea.
3
Department of Biotechnology, Graduate School of Biotechnology, Korea University, Seoul 136-713 Republic of Korea. Electronic address: junelee@korea.ac.kr.

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; EC50, 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.

KEYWORDS:

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

PMID:
24821375
DOI:
10.1016/j.bmcl.2014.04.019
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center