RRC ID 37923
著者 Sawada Y, Sakamoto Y, Toh M, Ohara N, Hatanaka Y, Naka A, Kishimoto Y, Kondo K, Iida K.
タイトル Milk-derived peptide Val-Pro-Pro (VPP) inhibits obesity-induced adipose inflammation via an angiotensin-converting enzyme (ACE) dependent cascade.
ジャーナル Mol Nutr Food Res
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.
巻・号 59(12)
ページ 2502-10
公開日 2015-12-1
DOI 10.1002/mnfr.201500324
PMID 26346532
MeSH Adipocytes / drug effects Adipocytes / metabolism Animals Cells, Cultured Coculture Techniques / methods Diet, High-Fat / adverse effects Gene Expression Regulation / drug effects Insulin Resistance Macrophages / drug effects Macrophages / pathology Male Mice, Inbred C57BL Milk / chemistry Obesity / complications* Obesity / metabolism Oligopeptides / pharmacology* Panniculitis / drug therapy* Panniculitis / etiology Panniculitis / metabolism Peptidyl-Dipeptidase A / genetics Peptidyl-Dipeptidase A / metabolism* Tumor Necrosis Factor-alpha / genetics
IF 5.309
引用数 17
WOS 分野 FOOD SCIENCE & TECHNOLOGY
リソース情報
ヒト・動物細胞 RAW 264(RCB0535)