The Dipeptide H-Trp-Arg-OH (WR) Is a PPARα Agonist and Reduces Hepatic Lipid Accumulation in Lipid-Loaded H4IIE Cells

被引:7
作者
Jia, Yaoyao [1 ]
Kim, Jong-Ho [1 ]
Nam, Bora [1 ]
Kim, Jiyoung [1 ]
Lee, Ji Hae [1 ]
Kim, Kyung Ok [3 ]
Hwang, Kwang Yeon [4 ]
Lee, Sung-Joon [1 ,2 ]
机构
[1] Korea Univ, Dept Biotechnol, Grad Sch Biotechnol, Coll Life Sci & Biotechnol, Seoul 136713, South Korea
[2] Korea Univ, Coll Life Sci & Biotechnol, Div Food Biosci & Technol, Seoul 136713, South Korea
[3] SEMPIO FOODS Co, Cheongwongun 363954, Chungcheongbukd, South Korea
[4] Korea Univ, Grad Sch Biotechnol, Dept Biosyst & Biotechnol, Seoul 136713, South Korea
基金
新加坡国家研究基金会;
关键词
Dipeptide; H-Trp-Arg-OH (WR); Lipid metabolism; PPAR alpha; ACTIVATED RECEPTOR-ALPHA; GAMMA ACTIVATORS; MICE LACKING; METABOLISM; EXPRESSION; GENES; ATHEROSCLEROSIS; STEATOHEPATITIS; TRIGLYCERIDES; MECHANISMS;
D O I
10.1007/s12010-014-1302-7
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Dipeptides absorbed by the intestinal epithelium are delivered to circulation, but their metabolic roles are not yet clearly understood. We investigated the biological activities of a dietary dipeptide, H-Trp-Arg-OH (WR), on the regulation of peroxisome proliferator-activated receptor (PPAR) alpha activity. Reporter gene assays revealed that WR dose-dependently induced PPAR alpha transactivation. Surface plasmon resonance experiments demonstrated that WR interacts directly with the PPAR alpha ligand binding domain, and time-resolved fluorescence energy transfer analyses revealed recruitment of a co-activator peptide, fluorescein-PGC1 alpha, to PPAR alpha, confirming the direct binding of WR to PPAR alpha and occurrence of conformational changes. WR induced cellular fatty acid uptake and the expression of PPAR alpha response genes in fatty acid oxidation, thus reducing intracellular triglyceride accumulation in lipid-loaded hepatocytes. In conclusion, the dietary dipeptide WR activates PPAR alpha and reduces hepatic lipid accumulation in lipid-loaded hepatocytes.
引用
收藏
页码:1211 / 1220
页数:10
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