Milk-derived peptide Val-Pro-Pro (VPP) inhibits obesity-induced adipose inflammation via an angiotensin-converting enzyme (ACE) dependent cascade.
METHODS
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.


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.


CONCLUSIONS
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.
Department of Nutrition and Food Science, Graduate School of Humanities and Sciences, Ochanomizu University, Tokyo, Japan.
Yoko
Y
Sawada
Department of Nutrition and Food Science, Graduate School of Humanities and Sciences, Ochanomizu University, Tokyo, Japan.
Yuri
Y
Sakamoto
Department of Nutrition and Food Science, Graduate School of Humanities and Sciences, Ochanomizu University, Tokyo, Japan.
Mariko
M
Toh
Department of Nutrition and Food Science, Graduate School of Humanities and Sciences, Ochanomizu University, Tokyo, Japan.
Nozomi
N
Ohara
Department of Nutrition and Food Science, Graduate School of Humanities and Sciences, Ochanomizu University, Tokyo, Japan.
Yuiko
Y
Hatanaka
Laboratory of Applied Nutrition, Faculty of Human Life and Environmental Sciences, Ochanomizu University, Tokyo, Japan.
Ayano
A
Naka
Endowed Research Department "Food for Health", Ochanomizu University, Tokyo, Japan.
Yoshimi
Y
Kishimoto
Endowed Research Department "Food for Health", Ochanomizu University, Tokyo, Japan.
Kazuo
K
Kondo
Department of Nutrition and Food Science, Graduate School of Humanities and Sciences, Ochanomizu University, Tokyo, Japan.
Kaoruko
K
Iida
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods; D059305:Diet, High-Fat / Q000009:adverse effects; D005786:Gene Expression Regulation / Q000187:drug effects; D007333:Insulin Resistance; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D008892:Milk / Q000737:chemistry; D009765:Obesity / Q000150:complications* / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology*; D015434:Panniculitis / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D009842:Oligopeptides; D014409:Tumor Necrosis Factor-alpha; C489031:valyl-prolyl-proline; D007703:Peptidyl-Dipeptidase A
Cytokine; Food-derived peptide; Inflammation; Obesity; Renin-angiotensin system