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

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Abstract

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) α activity. Reporter gene assays revealed that WR dose-dependently induced PPARα transactivation. Surface plasmon resonance experiments demonstrated that WR interacts directly with the PPARα ligand binding domain, and time-resolved fluorescence energy transfer analyses revealed recruitment of a co-activator peptide, fluorescein-PGC1α, to PPARα, confirming the direct binding of WR to PPARα and occurrence of conformational changes. WR induced cellular fatty acid uptake and the expression of PPARα response genes in fatty acid oxidation, thus reducing intracellular triglyceride accumulation in lipid-loaded hepatocytes. In conclusion, the dietary dipeptide WR activates PPARα and reduces hepatic lipid accumulation in lipid-loaded hepatocytes.

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Acknowledgments

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. 2013R1A2A2A01016176), and a grant (14162MFDS973) from Ministry of Food and Drug Safety in 2014.  The SPR instrument was provided by the Korea Basic Science Institute. We thank Professor Hyun-Gyu Song for the advice on FRET analysis.

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Authors and Affiliations

  1. Department of Biotechnology, Graduate School of Biotechnology, Korea University, Room 410, College of Life Sciences & Biotechnology EAST Bldg, Anam-5-ga, 136-713, Seoul, Republic of Korea

    Yaoyao Jia, Jong-Ho Kim, Bora Nam, Jiyoung Kim, Ji Hae Lee & Sung-Joon Lee

  2. Division of Food Bioscience and Technology, College of Life Sciences and Biotechnology, Korea University, 136-713, Seoul, Republic of Korea

    Sung-Joon Lee

  3. SEMPIO FOODS COMPANY, 183 Osongsaengmyeong 4ro, Osongeup, Cheongwongun, Chungcheongbukdo, Republic of Korea, 363-954

    Kyung Ok Kim

  4. Department of Biosystems & Biotechnology, Graduate School of Biotechnology, Korea University, Seoul, 136-713, Republic of Korea

    Kwang Yeon Hwang

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  1. Yaoyao Jia
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  2. Jong-Ho Kim
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  3. Bora Nam
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  4. Jiyoung Kim
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  5. Ji Hae Lee
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  6. Kyung Ok Kim
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  7. Kwang Yeon Hwang
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  8. Sung-Joon Lee
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Correspondence to Sung-Joon Lee.

Additional information

Yaoyao Jia and Jong-Ho Kim contributed equally to this paper.

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Jia, Y., Kim, JH., Nam, B. et al. The Dipeptide H-Trp-Arg-OH (WR) Is a PPARα Agonist and Reduces Hepatic Lipid Accumulation in Lipid-Loaded H4IIE Cells. Appl Biochem Biotechnol 175, 1211–1220 (2015). https://doi.org/10.1007/s12010-014-1302-7

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  • DOI: https://doi.org/10.1007/s12010-014-1302-7

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