Abstract
Red wine polyphenol extracts improve cardiovascular and metabolic disorders linked to obesity. Their vascular protection is mediated by the activation of the alpha isoform of the estrogen receptor (ERα). In the present study, we explored the effects of a grape seed extract (GSE) enriched in the flavan-3-ols procyanidin dimers on obesity-related cardiovascular and metabolic disorders; with a particular interest in the role/contribution of ERα. Ovariectomized wild type or ERα knockout (KO) mice were fed with standard or western diet, supplemented or not with GSE, for 12 weeks. Their body weight was monitored throughout the study, and an echocardiography was performed at the end of the treatment. Blood and tissues were collected for biochemical and functional analysis, including nitric oxide and oxidative stress measurement. Vascular reactivity and liver mitochondrial complexes activity were also analyzed. In western diet-fed mice, GSE reduced adiposity, plasma triglycerides, and oxidative stress in the heart, liver, adipose and skeletal tissues; but did not improve the vascular dysfunction. In western diet-fed mice, ERα deletion prevented or reduced the beneficial effects of GSE on plasma triglycerides and visceral adiposity. ERα deletion also prevented/reduced the anti-oxidant effect of GSE in the liver, but did not affect its capacity to reduce oxidative stress in the heart and adipose tissue. In conclusion, dietary supplementation of GSE attenuated features of metabolic syndrome partially through ERα-dependent mechanisms. This report highlights the therapeutic potential of polyphenols, and especially extract enriched in procyanidin dimers, against the metabolic disorders associated with excessive energy intake.
Highlights
Obesity represents a major health challenge in developed countries (Flegal et al, 2010; Malik et al, 2013) and contributes to increasing rates of cardiovascular and cerebrovascular events, type 2 diabetes, dyslipidaemia and metabolic diseases
We previously demonstrated in Zucker fatty rats that the red wine polyphenol (RWP) extract ProvinolsTM improves glucose and lipid metabolism, as well as endothelial and cardiac functions without affecting the body weight gain (Agouni et al, 2009)
grape seed extract (GSE) supplementation did not modify oxidative stress in mice fed with standard diet, it tended to decrease reactive oxygen species (ROS) level in western diet group (Figure 6G). These results suggest that, in the heart, GSE was able to normalize the increased level of ROS induced by western diet through a mechanism independent of estrogen receptor alpha (ERα)
Summary
Obesity represents a major health challenge in developed countries (Flegal et al, 2010; Malik et al, 2013) and contributes to increasing rates of cardiovascular and cerebrovascular events, type 2 diabetes, dyslipidaemia and metabolic diseases. Pharmacological and dietary interventions represent promising strategies for both weight reduction and improving associated cardiometabolic risk (Ahluwalia et al, 2013; Sweeting et al, 2015). Among these dietary approaches, the use of nutraceuticals, has attracted great interest in the recent years (Magrone et al, 2013; Remely et al, 2015); including the supplementation with polyphenols, bioactive compounds from vegetables and fruits best known for their antioxidant properties (Duthie et al, 2003; Fraga et al, 2010). ProvinolsTM is mainly composed of the flavonoids flavanols and anthocyanins, which are described as the most effective classes of polyphenols (Chalopin et al, 2010)
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