Oral administration of the milk casein-derived tripeptide Val-Pro-Pro attenuates high-fat diet-induced adipose tissue inflammation in mice

Abstract

Inflammation of adipose tissue triggers the metabolic syndrome, atherosclerosis and CHD. In the present study, we investigated whether the milk casein-derived tripeptide valine-proline-proline (VPP) has an anti-inflammatory effect on the adipose tissue of high-fat diet (HFD)-fed mice. Male C57BL/6J mice (7 weeks of age) were fed ad libitum with either a HFD and plain tap water (HFD group) or a HFD and water containing 0·3 mg VPP/ml (HFDþVPP group) for 10 weeks. The results showed that the expression level of CD18 in the peripheral blood monocytes of the HFDþ VPP group was significantly decreased compared with the level observed in those of the HFD group. Activated monocytes and pro-inflammatory macrophages were accumulated in the stromal vascular fractions of the adipose tissue from HFD-fed mice, which were significantly decreased in those supplemented with VPP. The formation of crown-like structures rich in pro-inflammatory macrophages was also significantly reduced in the adipose tissue of mice administered with VPP. Real-time PCR analysis revealed that the expression of monocyte chemoattractant protein-1 and that of the pro-inflammatory cytokine IL-6 in adipose tissue tend to be lower in the HFDþ VPP group than in the HFD group. These observations indicate that oral administration of VPP exerts an anti-inflammatory effect on the adipose tissue of HFD-fed mice, which may eventually lead to the primary prevention of chronic inflammation-related diseases.Key words: Casein-derived tripeptides: Inflammation: High-fat diet: Adipose tissue: Macrophages Lifestyle-related metabolic disorders such as hypertension, diabetes and dyslipidaemia play a crucial role in the development of atherosclerosis and CVD. Low-grade, but chronic inflammation is considered to be involved in the development of metabolic disorders. Among these, inflammation of adipose tissue is associated with obesity and directly promotes systemic low-grade inflammation and metabolic dysfunction (1 -3) . It has been reported that two naturally existing milk caseinderived bioactive tripeptides, isoleucine-proline-proline (IPP) and valine-proline-proline (VPP), produced during lactic acid bacteria fermentation or in casein hydrolysates, inhibit angiotensin-converting enzyme activity (4,5) , and foods containing these peptides reduce blood pressure in several clinical trials (6,7) . VPP and IPP have also been shown to induce the production of vasodilative substances including NO in human umbilical vein endothelial cells and isolated rat arterial vessels (8) . Several recent clinical trials have shown that intake of casein hydrolysate containing VPP and IPP for 1 week improved vascular endothelial dysfunction without affecting systemic blood pressure in subjects with untreated stage-I hypertension (9) . Moreover, an 8-week intervention using the same regimen has been shown to decrease central systolic blood pressure and arterial stiffness (brachial -ankle pulse wave velocity and carotid arterial compliance) (10,11) .Animal studies have revealed th...

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