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-1ß 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-1ß 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.
Subject(s)
Obesity/complications , Oligopeptides/pharmacology , Panniculitis/drug therapy , Peptidyl-Dipeptidase A/metabolism , 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/metabolism , Panniculitis/etiology , Panniculitis/metabolism , Peptidyl-Dipeptidase A/genetics , Tumor Necrosis Factor-alpha/geneticsABSTRACT
SCOPE: Daidzein was recently reported to act like an activator of peroxisome proliferator-activated receptor γ (PPARγ) thereby enhancing differentiation of adipocytes. Although PPARγ plays a role in adipokine expression, it has not been well researched whether daidzein affects expression of adipokines. This study aimed to clarify the effects of daidzein on proinflammatory adipokines and adipose inflammation causing insulin resistance in obesity. METHODS AND RESULTS: 3T3-L1 adipocytes were treated with daidzein or genistein. Diet-induced obese C57BL/6J mice were fed high-fat high-sucrose diets with daidzein (1.0 g/kg chow) for 12 wk. The results showed that both isoflavones, especially daidzein, stimulated adipogenic differentiation in 3T3-L1 adipocytes with the activation of PPARγ. Daidzein also increased adiponectin expression and decreased MCP-1 expression with the consistent regulation of their secretion. In obese mice, daidzein inhibited hypertrophy in fat cell size and improved insulin sensitivity, concomitant with upregulation of PPARγ in fat tissue. Decreased expression of MCP-1 and TNF-α, and increased expression of adiponectin were also observed in adipose tissue of daidzein-fed mice. Additionally, daidzein administration significantly inhibited macrophage accumulation in adipose tissue. CONCLUSION: Daidzein regulates adipokine expression through the PPARγ, thereby improving the adverse effects of adipose inflammation, such as insulin resistance, in obesity.
