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ラクトフェリンは哺乳類の乳中に豊富に含まれる糖タンパク質であり，感染防御，免疫賦活など，様々な生理機能を持つことが知られている．我々は腸溶化したラクトフェリンに内臓脂肪低減効果という新機能を見出したことから，その機能性食品への展開と作用機序解明に向けて様々な検討を行ってきた．特に，脂肪分解促進効果の作用機序解析においては，プロテオーム解析技術を活用することで変動因子の抽出やラクトフェリン受容体の同定を行い，分子生物学的な解析による裏付けを重ねることで詳細な分子機構を解明することができた．2015年の「機能性表示食品」制度のスタートなど，近年の食品業界を取り巻く環境は刻一刻と変化しており，より高いレベルの研究成果が求められるようになってきている．今後も，人々の健康の維持・増進に貢献できる，確固たるエビデンスを持った製品を開発すべく，学際領域の知識・技術との連携を活かして取組んでいきたい．

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. več