Premium
The Dipeptide H‐Trp‐Glu‐OH Shows Agonistic Activity to PPAR‐α, Reducing Hepatic Lipid Accumulation in Lipid‐loaded H4IIE Cells
Author(s) -
Jia Yaoyao,
Lee SungJoon
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1079.50
Subject(s) - chemistry , lipid metabolism , peroxisome proliferator activated receptor , tryptophan , receptor , biochemistry , medicine , biophysics , biology , amino acid
A group of dipeptides containing tryptophan (Trp) can be directly absorbed by intestine and would show significant metabolic effects. We investigated whether Trp‐containing dipeptides could reduce hepatic lipid accumulation by activating peroxisome proliferator‐activated receptors (PPAR)‐α, a key transcription factor in the regulation of hepatic lipid metabolism. We investigate the effect of H‐Trp‐Glu‐OH to the ligand binding domain (LBD) of PPAR‐α by surface plasmon resonance experiments, and showed that H‐Trp‐Glu‐OH bind with PPAR‐α‐LBD directly with dissociation constants of 120 μM. Binding of H‐Trp‐Glu‐OH activated PPAR‐α with half‐maximal effective concentrations of 83 μM measured by time‐resolved fluorescence energy transfer analyses. PPAR‐α is a regulator in hepatic lipid metabolism, so we investigated the effect of H‐Trp‐Glu‐OH in lipid‐loaded H4IIE cells. H‐Trp‐Glu‐OH stimulation reduced cellular cholesterol and triglyceride accumulation significantly in lipid‐loaded hepatocytes. In conclusion, H‐Trp‐Glu‐OH reduces hepatic lipid accumulation in lipid‐loaded hepatocytes via activate PPAR‐α.