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Milk‐derived peptide Val‐Pro‐Pro (VPP) inhibits obesity‐induced adipose inflammation via an angiotensin‐converting enzyme (ACE) dependent cascade
Author(s) -
Sawada Yoko,
Sakamoto Yuri,
Toh Mariko,
Ohara Nozomi,
Hatanaka Yuiko,
Naka Ayano,
Kishimoto Yoshimi,
Kondo Kazuo,
Iida Kaoruko
Publication year - 2015
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201500324
Subject(s) - adipose tissue , adipocyte , insulin resistance , medicine , endocrinology , tumor necrosis factor alpha , inflammation , 3t3 l1 , chemistry , insulin , proinflammatory cytokine , biology
Scope This study aimed to examine the effects of Val‐Pro‐Pro (VPP), a food‐derived peptide with an angiotensin‐converting enzyme (ACE) inhibitory property, on obesity‐linked insulin resistance, and adipose inflammation in vivo and in vitro. Methods and results C57BL/6J mice were fed high‐fat high‐sucrose diet and VPP (0.1% in water) for 4 months. For in vitro analysis, coculture of 3T3‐L1 adipocytes overexpressing either ACE (3T3‐ACE) or green fluorescent protein (3T3‐GFP) and RAW264 macrophages was conducted with VPP. In diet‐induced obese mice, VPP improved insulin sensitivity, concomitant with a significant decrease in tumor necrosis factor α (TNF‐α) and IL‐1β expression in adipose tissue, with a tendency ( p = 0.06) toward decreased CC chemokine ligand 5 expression. Additionally, VPP administration inhibited macrophage accumulation and activation in fat tissues. In vitro, VPP attenuated TNF‐α mRNA induced by ACE overexpression in 3T3‐L1 adipocytes. TNF‐α and IL‐1β expression decreased following VPP treatment of RAW264 macrophage and 3T3‐ACE adipocyte cocultures, but not in RAW264‐3T3‐GFP adipocyte cocultures. Conclusion Our data suggest that VPP inhibits adipose inflammation in the interaction between adipocytes and macrophages, acting as an ACE inhibitor, thereby improving obesity‐related insulin resistance. Thus, ingestion of VPP may be a viable protective and therapeutic strategy for insulin resistance and obesity‐associated adipose inflammation.