PMID- 27322965 OWN - NLM STAT- MEDLINE DCOM- 20170322 LR - 20231213 IS - 1557-7600 (Electronic) IS - 1096-620X (Linking) VI - 19 IP - 7 DP - 2016 Jul TI - The Soy Peptide Phe-Leu-Val Reduces TNFalpha-Induced Inflammatory Response and Insulin Resistance in Adipocytes. PG - 678-85 LID - 10.1089/jmf.2016.3685 [doi] AB - 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 (TNFalpha) 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 (TNFalpha, MCP-1, and IL-6) from both TNFalpha-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 IkappaB kinase (IKK), and the downregulation of IkappaBalpha 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 TNFalpha-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. FAU - Kwak, Su-Jin AU - Kwak SJ AD - 1 Department of Food Science and Nutrition, University of Ulsan , Ulsan, Korea. FAU - Kim, Chu-Sook AU - Kim CS AD - 1 Department of Food Science and Nutrition, University of Ulsan , Ulsan, Korea. FAU - Choi, Myung-Sook AU - Choi MS AD - 2 Department of Food Science and Nutrition, Center for Food and Nutritional Genomics Research, Kyungpook National University , Daegu, Korea. FAU - Park, Taesun AU - Park T AD - 3 Department of Food and Nutrition, Yonsei University , Seoul, Korea. FAU - Sung, Mi-Kyung AU - Sung MK AD - 4 Department of Food and Nutrition, Sookmyung Women's University , Seoul, Korea. FAU - Yun, Jong Won AU - Yun JW AD - 5 Department of Biotechnology, Daegu University , Gyeongbuk, Korea. FAU - Yoo, Hoon AU - Yoo H AD - 6 Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chosun University , Gwangju, Korea. FAU - Mine, Yoshinori AU - Mine Y AD - 7 Department of Food Science, University of Guelph , Guelph, ON, Canada . FAU - Yu, Rina AU - Yu R AD - 1 Department of Food Science and Nutrition, University of Ulsan , Ulsan, Korea. LA - eng PT - Journal Article DEP - 20160620 PL - United States TA - J Med Food JT - Journal of medicinal food JID - 9812512 RN - 0 (Anti-Inflammatory Agents) RN - 0 (CCL2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Cytokines) RN - 0 (Oligopeptides) RN - 0 (Symporters) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (hydrogen-coupled oligopeptide transporter PepT2) RN - 0 (phenylalanyl-leucyl-valine) SB - IM MH - Adipocytes/*drug effects/metabolism MH - *Anti-Inflammatory Agents MH - Chemokine CCL2/metabolism MH - Cytokines/metabolism MH - Humans MH - Inflammation/prevention & control MH - *Insulin Resistance MH - Obesity/metabolism MH - Oligopeptides/*pharmacology MH - Signal Transduction/drug effects MH - Glycine max/*chemistry MH - Symporters/antagonists & inhibitors/metabolism MH - Tumor Necrosis Factor-alpha/metabolism/*pharmacology OTO - NOTNLM OT - adipocytes OT - inflammation OT - insulin resistance OT - obesity OT - soy peptide EDAT- 2016/06/21 06:00 MHDA- 2017/03/23 06:00 CRDT- 2016/06/21 06:00 PHST- 2016/06/21 06:00 [entrez] PHST- 2016/06/21 06:00 [pubmed] PHST- 2017/03/23 06:00 [medline] AID - 10.1089/jmf.2016.3685 [doi] PST - ppublish SO - J Med Food. 2016 Jul;19(7):678-85. doi: 10.1089/jmf.2016.3685. Epub 2016 Jun 20.