The Soy Peptide Phe-Leu-Val Reduces TNFα-Induced Inflammatory Response and Insulin Resistance in Adipocytes.
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.
1 Department of Food Science and Nutrition, University of Ulsan , Ulsan, Korea.
Su-Jin
SJ
Kwak
1 Department of Food Science and Nutrition, University of Ulsan , Ulsan, Korea.
Chu-Sook
CS
Kim
2 Department of Food Science and Nutrition, Center for Food and Nutritional Genomics Research, Kyungpook National University , Daegu, Korea.
Myung-Sook
MS
Choi
3 Department of Food and Nutrition, Yonsei University , Seoul, Korea.
Taesun
T
Park
4 Department of Food and Nutrition, Sookmyung Women's University , Seoul, Korea.
Mi-Kyung
MK
Sung
5 Department of Biotechnology, Daegu University , Gyeongbuk, Korea.
Jong Won
JW
Yun
6 Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chosun University , Gwangju, Korea.
Hoon
H
Yoo
7 Department of Food Science, University of Guelph , Guelph, ON, Canada .
Yoshinori
Y
Mine
1 Department of Food Science and Nutrition, University of Ulsan , Ulsan, Korea.
Rina
R
Yu
D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000893:Anti-Inflammatory Agents; D018932:Chemokine CCL2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000517:prevention & control; D007333:Insulin Resistance; D009765:Obesity / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013025:Glycine max / Q000737:chemistry*; D027981:Symporters / Q000037:antagonists & inhibitors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016207:Cytokines; D009842:Oligopeptides; D027981:Symporters; D014409:Tumor Necrosis Factor-alpha; C093694:hydrogen-coupled oligopeptide transporter PepT2; C000615816:phenylalanyl-leucyl-valine
adipocytes; inflammation; insulin resistance; obesity; soy peptide