Application of Proteomic Approach for Developing Functional Food Products:Analysis of the Mechanism of Action of Lactoferrin for Reducing Visceral Fat

DOI
  • Seki Keiko
    Research and Development Headquarters, Lion Corporation Advanced Medical Research Center, Yokohama City University
  • Ono Tomoji
    Research and Development Headquarters, Lion Corporation Advanced Medical Research Center, Yokohama City University
  • Nakamura Kanae
    Research and Development Headquarters, Lion Corporation
  • Morishita Satoru
    Research and Development Headquarters, Lion Corporation
  • Murakoshi Michiaki
    Research and Development Headquarters, Lion Corporation Advanced Medical Research Center, Yokohama City University

Bibliographic Information

Other Title
  • プロテオミクスの機能性食品開発研究への活用～ラクトフェリンの内臓脂肪低減メカニズムの解析～

Description

<p>Lactoferrin (LF) is a multi-functional milk protein. We previously reported that enteric-coated LF decreased visceral fat accumulation in a clinical trial. Animal studies revealed that ingested LF was delivered to mesenteric fat and in vitro experiments showed that LF promoted the lipolysis of mature adipocytes. Therefore, we attempted to identify the mechanism underlying lipolysis induced by LF. Pre-adipocytes derived from mesenteric fat tissue of male rats were cultured and differentiated into their mature form, and cells were collected at various time points after the addition of LF. Proteomic analysis revealed changes in the expression levels of proteins related to the cAMP and ERK signaling pathways. Therefore, we validated the activation of these pathways using Western blotting, ELISA, and pull-down assay. We then detected the increased phosphorylation level of CREB, a downstream transcription factor of both cAMP and ERK signaling pathways, which regulates the expression levels of enzymes involved in lipolysis. We also attempted to identify LF receptors on adipocytes. We again used a proteomic approach to analyze LF binding proteins. Finally, we identified low-density lipoprotein receptor-related protein 1 (LRP1) as the most reliable candidate for the LF receptor. Silencing analysis of LRP1 showed attenuated lipolytic activity of LF, and we concluded that LRP1 is the LF receptor for sending lipolytic signals by LF on adipocytes. LF binds LRP1 and activates the cAMP/ERK signaling pathway via phosphorylation and transcriptional regulation, and then these effects result in the promotion of lipolysis in mature adipocytes.</p>

Journal

  • Proteome Letters

    Proteome Letters 1 (1), 25-35, 2016

    Japanese Proteomics Society

Keywords

Details 詳細情報について

  • CRID
    1390282681206254592
  • NII Article ID
    130006743366
  • DOI
    10.14889/jpros.1.1_25
  • ISSN
    24322776
  • Text Lang
    ja
  • Data Source
    • JaLC
    • CiNii Articles
  • Abstract License Flag
    Disallowed

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