The Soy Peptide Phe-Leu-Val Reduces TNFα-Induced Inflammatory Response and Insulin Resistance in Adipocytes

Su Jin Kwak, Chu Sook Kim, Myung Sook Choi, Taesun Park, Mi Kyung Sung, Jong Won Yun, Hoon Yoo, Yoshinori Mine, Rina Yu

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)


Obesity-induced adipose inflammation plays a crucial role in the development of obesity-induced metabolic disorders such as insulin resistance and type 2 diabetes. In the presence of obesity, hypertrophic adipocytes release inflammatory mediators, including tumor necrosis factor-alpha (TNFα) and monocyte chemoattractant protein-1 (MCP-1), which enhance the recruitment and activation of macrophages, and in turn augment adipose inflammation. We demonstrate that the soy peptide Phe-Leu-Val (FLV) reduces inflammatory responses and insulin resistance in mature adipocytes. Specifically, the soy peptide FLV inhibits the release of inflammatory cytokines (TNFα, MCP-1, and IL-6) from both TNFα-stimulated adipocytes and cocultured adipocytes/macrophages. This inhibition is mediated by the inactivation of the inflammatory signaling molecules c-Jun N-terminal kinase (JNK) and IκB kinase (IKK), and the downregulation of IκBα in the adipocytes. In addition, soy peptide FLV enhances insulin responsiveness and increases glucose uptake in adipocytes. More importantly, we, for the first time, found that adipocytes express peptide transporter 2 (PepT2) protein, and the beneficial action of the soy peptide FLV was disrupted by the peptide transporter inhibitor GlySar. These findings suggest that soy peptide FLV is transported into adipocytes by PepT2 and then downregulates TNFα-induced inflammatory signaling, thereby increasing insulin responsiveness in the cells. The soy peptide FLV, therefore, has the potential to prevent obesity-induced adipose inflammation and insulin resistance.

Original languageEnglish
Pages (from-to)678-685
Number of pages8
JournalJournal of medicinal food
Issue number7
Publication statusPublished - 2016 Jul

Bibliographical note

Funding Information:
This work was supported by the Science Research Center program (Center for Food and Nutritional Genomics Research: Grant no. 2015R1A5A6001906) of the National Research Foundation of Korea funded by the Ministry of Education, Science, and Technology and by Fuji Foundation for Protein Research.

Publisher Copyright:
© 2016 Mary Ann Liebert, Inc., and Korean Society of Food Science and Nutrition.

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Nutrition and Dietetics


Dive into the research topics of 'The Soy Peptide Phe-Leu-Val Reduces TNFα-Induced Inflammatory Response and Insulin Resistance in Adipocytes'. Together they form a unique fingerprint.

Cite this