Key result
In diet-induced obese mice, VPP administration improved insulin sensitivity and decreased TNF-α and IL-1β expression in adipose tissue, acting as an ACE inhibitor.
Why the study?
Does Val-Pro-Pro (VPP) improve obesity-linked insulin resistance and adipose inflammation in high-fat diet-fed mice?
Does Val-Pro-Pro (VPP) improve obesity-linked insulin resistance and adipose inflammation in high-fat diet-fed mice?
p-value: p=0.06
The milk-derived peptide VPP inhibits obesity-induced adipose inflammation and improves insulin resistance via an ACE-dependent mechanism in preclinical models.
VPP attenuates diet-induced insulin resistance in mice; leaves open translation to human metabolic disease.
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.
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Sawada et al. (2015) studied Obesity-linked insulin resistance and adipose inflammation. Val-Pro-Pro (VPP) was evaluated on Insulin sensitivity and adipose inflammation (TNF-α, IL-1β expression) (p=0.06). In diet-induced obese mice, VPP administration improved insulin sensitivity and decreased TNF-α and IL-1β expression in adipose tissue, acting as an ACE inhibitor.
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