A central role of eNOS in the protective effect of wine against metabolic syndrome

Abstract

The positive health effects derived from moderate wine consumption are pleiotropic. They appear as improvements in cardiovascular risk factors such as plasma lipids, haemostatic mechanisms, endothelial function and antioxidant defences. The active principles would be ethanol and mainly polyphenols. Results from our and other laboratories support the unifying hypothesis that the improvements in risk factors after red wine consumption are mediated by endothelial nitric oxide synthase (eNOS). Many genes are involved, but the participation of eNOS would be a constant feature. The metabolic syndrome is a cluster of metabolic risk factors associated with high risk of cardiovascular disease (CVD). The National Cholesterol Education Programmmes Adult Treatment Panel III (NCEPATP III) clinical definition of the metabolic syndrome requires the presence of at least three risk factors, from among abdominal obesity, high plasma triacylglycerols, low plasma HDL, high blood pressure and high fasting plasma glucose. The molecular mechanisms responsible for the metabolic syndrome are not known. Since metabolic syndrome apparently affects 10-30% of the population in the world, research on its pathogenesis and control is needed. The recent finding that eNOS knockout mice present a cluster of cardiovascular risk factors comparable to those of the metabolic syndrome suggests that defects in eNOS function may cause human metabolic syndrome. These mice are hypertensive, insulin resistant and dyslipidemic. Further support for a pathogenic role of eNOS comes from the finding in humans that eNOS polymorphisms associate with insulin resistance and diabetes, with hypertension, with inflammatory and oxidative stress markers and with albuminuria. So, the data sustain the hypothesis that eNOS enhancement should reduce metabolic syndrome incidence and its consequences. Therefore red wine, since it enhances eNOS function, should be considered as a potential tool for the control of metabolic syndrome. This hypothesis is supported by epidemiological observations and needs experimental validation in human intervention studies.

Association between Alcohol Consumption and Hypertension

“…[30][31][32][33] Some authors have indicated that red wine may enhance endothelial nitric oxide synthase function and antagonize the development of endothelial dysfunction and atherosclerosis. 34,35) A few studies have speculated that the protective effect of light to moderate alcohol consumption on the risk of hypertension may reflect an additional pathway by which light to moderate alcohol intake reduces the risk of coronary heart disease and death. 9) However, there is counter evidence to this hypothesis.…”

Polyphenolic phytochemicals – just antioxidants or much more?

“…Under-expression of endothelial nitric oxide synthase (eNOS) is strongly implicated in metabolic syndrome. Red wine, a rich source of PPs, enhances eNOS function [144]. PPs can clearly regulate the absorption of nutrients from the gut, but also appear to benefit gut health directly.…”

Wine and Health: A Review

“…These risk factors include abdominal obesity, high plasma triacylglycerols, low plasma HDL, high blood pressure and high fasting plasma glucose. Several reviews have presented evidence that moderate wine consumption may prevent metabolic syndrome and its related medical complications (Leighton et al 2006. A mechanism that may be important is the ability of red wine components to enhance the function of endothelial NO synthase (eNOS), which may not function properly in metabolic syndrome patients (Leighton et al 2006).…”