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

doi:10.1016/j.bmcl.2014.04.019

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 journal › Article › peer-review

10 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 (K_D, 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 language	English
Pages (from-to)	2957-2962
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	24
Issue number	13
DOIs	https://doi.org/10.1016/j.bmcl.2014.04.019
Publication status	Published - 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

Access to Document

10.1016/j.bmcl.2014.04.019

Cite this

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. / Jia, Yaoyao; Kim, Jong Ho; Nam, Bora et al.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 24, No. 13, 01.07.2014, p. 2957-2962.

Research output: Contribution to journal › Article › peer-review

@article{2b3d95a359a54505a17d18e77f2159f1,

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; 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.",

keywords = "Dipeptide, H-Trp-Glu-OH (WE), Lipid metabolism, Liver, PPARα",

author = "Yaoyao Jia and Kim, {Jong Ho} and Bora Nam and Jiyoung Kim and Lee, {Ji Hae} and Hwang, {Kwang Yeon} and Lee, {Sung Joon}",

note = "Funding Information: This research was supported by the High Value-Added Food Technology Development Program of iPET (Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries), the Ministry for Food, Agriculture, Forestry and Fisheries, Republic of Korea ( 111022-03-3-HD110 ) and by the Basic Science Research Program of the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science and Technology ( 2013R1A2A2A01016176 ).",

year = "2014",

month = jul,

day = "1",

doi = "10.1016/j.bmcl.2014.04.019",

language = "English",

volume = "24",

pages = "2957--2962",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Limited",

number = "13",

}

TY - JOUR

T1 - 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

AU - Jia, Yaoyao

AU - Kim, Jong Ho

AU - Nam, Bora

AU - Kim, Jiyoung

AU - Lee, Ji Hae

AU - Hwang, Kwang Yeon

AU - Lee, Sung Joon

N1 - Funding Information: This research was supported by the High Value-Added Food Technology Development Program of iPET (Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries), the Ministry for Food, Agriculture, Forestry and Fisheries, Republic of Korea ( 111022-03-3-HD110 ) and by the Basic Science Research Program of the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science and Technology ( 2013R1A2A2A01016176 ).

PY - 2014/7/1

Y1 - 2014/7/1

N2 - 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.

AB - 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.

KW - Dipeptide

KW - H-Trp-Glu-OH (WE)

KW - Lipid metabolism

KW - Liver

KW - PPARα

UR - http://www.scopus.com/inward/record.url?scp=84901749957&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2014.04.019

DO - 10.1016/j.bmcl.2014.04.019

M3 - Article

C2 - 24821375

AN - SCOPUS:84901749957

SN - 0960-894X

VL - 24

SP - 2957

EP - 2962

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 13

ER -

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

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this