title: 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.
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.
authors.affiliation: Department of Biotechnology, Graduate School of Biotechnology, Korea University, Seoul 136-713 Republic of Korea.
authors.forename: Yaoyao
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Department of Biotechnology, Graduate School of Biotechnology, Korea University, Seoul 136-713 Republic of Korea.
authors.forename: Jong-Ho
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, Graduate School of Biotechnology, Korea University, Seoul 136-713 Republic of Korea.
authors.forename: Bora
authors.initials: B
authors.lastname: Nam
authors.affiliation: Department of Biotechnology, Graduate School of Biotechnology, Korea University, Seoul 136-713 Republic of Korea.
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, Graduate School of Biotechnology, Korea University, Seoul 136-713 Republic of Korea.
authors.forename: Ji Hae
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Biosystems & Biotechnology, Graduate School of Biotechnology, Korea University, Seoul 136-713 Republic of Korea.
authors.forename: Kwang-Yeon
authors.initials: KY
authors.lastname: Hwang
authors.affiliation: Department of Biotechnology, Graduate School of Biotechnology, Korea University, Seoul 136-713 Republic of Korea. Electronic address: junelee@korea.ac.kr.
authors.forename: Sung-Joon
authors.initials: SJ
authors.lastname: Lee
mesh_terms: D002460:Cell Line; D004151:Dipeptides / Q000737:chemistry / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects*; D008055:Lipids / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D015394:Molecular Structure; D047493:PPAR alpha / Q000819:agonists* / Q000235:genetics; D013329:Structure-Activity Relationship
chemical_list: D004151:Dipeptides; D008055:Lipids; D047493:PPAR alpha
keywords: Dipeptide; H-Trp-Glu-OH (WE); Lipid metabolism; Liver; PPARα