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

Abstract

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.

• Authors: Yoko Sawada, Yuri Sakamoto, Mariko Toh, Nozomi Ohara, Yuiko Hatanaka, Ayano Naka, Yoshimi Kishimoto, Kazuo Kondo, Kaoruko Iida
• Journal: Molecular nutrition & food research (Mol Nutr Food Res) Vol. 59 Issue 12 Pg. 2502-10 (Dec 2015) ISSN: 1613-4133 [Electronic] Germany
• PMID: 26346532 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Oligopeptides
• Tumor Necrosis Factor-alpha
• valyl-prolyl-proline
• Peptidyl-Dipeptidase A

Topics

• Adipocytes (drug effects, metabolism)
• Animals
• Cells, Cultured
• Coculture Techniques (methods)
• Diet, High-Fat (adverse effects)
• Gene Expression Regulation (drug effects)
• Insulin Resistance
• Macrophages (drug effects, pathology)
• Male
• Mice, Inbred C57BL
• Milk (chemistry)
• Obesity (complications, metabolism)
• Oligopeptides (pharmacology)
• Panniculitis (drug therapy, etiology, metabolism)
• Peptidyl-Dipeptidase A (genetics, metabolism)
• Tumor Necrosis Factor-alpha (genetics)