To evaluate the effects of grape polyphenols on plasma lipids, inflammatory cytokines, and oxidative stress, 24 pre- and 20 postmenopausal women were randomly assigned to consume 36 g of a lyophilized grape powder (LGP) or a placebo for 4 wk. The LGP consisted of 92% carbohydrate and was rich in flavans, anthocyanins, quercetin, myricetin, kaempferol, and resveratrol. After a 3-wk washout period, subjects were assigned to the alternate treatment for an additional 4 wk. The placebo consisted of an equal ratio of fructose and dextrose and was similar in appearance and energy content (554 kJ) to LGP. Plasma triglyceride concentrations were reduced by 15 and 6% in pre- and postmenopausal women, respectively (P < 0.01) after LGP supplementation. In addition, plasma LDL cholesterol and apolipoproteins B and E were lower due to LGP treatment (P < 0.05). Further, cholesterol ester transfer protein activity was decreased by approximately 15% with intake of LGP (P < 0.05). In contrast to these beneficial effects on plasma lipids, LDL oxidation was not modified by LGP treatment. However, whole-body oxidative stress as measured by urinary F(2)-isoprostanes was significantly reduced after LGP supplementation. LGP also decreased the levels of plasma tumor necrosis factor-alpha, which plays a major role in the inflammation process. Through alterations in lipoprotein metabolism, oxidative stress, and inflammatory markers, LGP intake beneficially affected key risk factors for coronary heart disease in both pre- and postmenopausal women.

Dietary polyphenols have been shown to possess cardioprotective effects. For example, the most noted role of grape polyphenols is in the French Paradox, in which a diet high in saturated fat accompanied by regular consumption of red wine is associated with a low risk of coronary heart disease (CHD). Initially, the paradox was thought to be driven by the postulated major action of grape polyphenols in inhibiting LDL oxidation. Although many studies have shown inhibitory effects of polyphenols on LDL oxidation, there have been an equal number of studies that showed a null effect on this variable. Although there are contrasting viewpoints on the effects of polyphenols on LDL oxidation variables, there is increasing evidence that these compounds possess additional cardioprotective functions including altering hepatic cholesterol absorption, triglyceride assembly and secretion, the processing of lipoproteins in plasma, and inflammation. It is the purpose of this review to examine recent information on the multiple functions of dietary polyphenols, with an emphasis on grape polyphenols, in decreasing the risk of CHD by improving plasma lipid profiles and reducing inflammation.

The link between adiponectin levels and a strong marker of inflammation, CRP, is independent of insulin resistance and adiposity in obese children and adolescents. Adiponectin may be one of the signals linking inflammation and obesity. Thus, adiponectin may function as a biomarker of the metabolic syndrome in childhood obesity.

The prevalence of insulin resistance and type 2 diabetes (T2D) in obese youth is rapidly increasing, especially in Hispanics and African Americans compared to Caucasians. Insulin resistance is known to be associated with increases in intramyocellular (IMCL) and hepatic fat content. We determined if there are ethnic differences in IMCL and hepatic fat content in a multiethnic cohort of 55 obese adolescents. We used 1H magnetic resonance spectroscopy (MRS) to quantify IMCL levels in the soleus muscle, oral glucose tolerance testing to estimate insulin sensitivity, magnetic resonance imaging (MRI) to measure abdominal fat distribution. Liver fat content was measured by fast–MRI. Despite similar age and % total body fat among the groups, IMCL was significantly higher in the Hispanics (1.71% [1.43%, 2.0%]) than in the African-Americans (1.04% [0.75%, 1.34%], p = 0.013) and the Caucasians (1.2% [0.94%, 1.5%], p = 0.04). Liver fat content was undetectable in the African Americans whereas it was two fold higher than normal in both Caucasians and Hispanics. Visceral fat was significantly lower in African Americans (41.5 cm2 [34.6, 49.6]) and was similar in Caucasians (65.2 cm2 [55.9, 76.0]) and Hispanics (70.5 cm2 [59.9, 83.1]). In a multiple regression analysis, we found that ethnicity independent of age, gender and % body fat accounts for 10% of the difference in IMCL. Our study indicates that obese Hispanic adolescents have a greater IMCL lipid content than both Caucasians and African Americans, of comparable weight, age and gender. Excessive accumulation of fat in the liver was found in both Caucasian and Hispanic groups as opposed to virtually undetectable levels in the African Americans. Thus, irrespective of obesity, there seem to be some clear ethnic differences in the amount of lipid accumulated in skeletal muscle, liver and abdominal cavity.

OBJECTIVE -Among other metabolic consequences, a dyslipidemic profile often accompanies childhood obesity. In adults, type 2 diabetes and hepatic steatosis have been shown to alter lipoprotein subclass distribution and size; however, these alterations have not yet been shown in children or adolescents. Therefore, our objective was to determine the effect of hepatic steatosis on lipoprotein concentration and size in obese adolescents.RESEARCH DESIGN AND METHODS -Using fast magnetic resonance imaging, we measured intrahepatic fat content in 49 obese adolescents with normal glucose tolerance. The presence or absence of hepatic steatosis was determined by a threshold value for hepatic fat fraction (HFF) of 5.5%; therefore, the cohort was divided into two groups (HFF Ͼ or Ͻ5.5%). Fasting lipoprotein subclasses were determined using nuclear magnetic resonance spectroscopy.RESULTS -Overall, the high-HFF group had 88% higher concentrations of large VLDL compared with the low-HFF group (P Ͻ 0.001). Likewise, the high-HFF group had significantly higher concentrations of small dense LDL (P Ͻ 0.007); however, the low-HFF group had significantly higher concentrations of large HDL (P Ͻ 0.001). Stepwise multiple regression analysis revealed that high HFF was the strongest single correlate, accounting for 32.6% of the variance in large VLDL concentrations (P Ͻ 0.002).CONCLUSIONS -The presence of fatty liver was associated with a pronounced dyslipidemic profile characterized by large VLDL, small dense LDL, and decreased large HDL concentrations. This proatherogenic phenotype was strongly related to the intrahepatic lipid content. Diabetes Care 30:3093-3098, 2007S tudies from autopsies on 742 children (aged 2-19 years) reported fatty liver prevalence at 9.6%, and in obese children this rate increased to an alarming 38% (1). An imbalance between fatty acid flux and utilization and VLDL secretion leads to an accumulation of triglycerides within the hepatocytes and ultimately to hepatic steatosis (2). It is becoming increasingly clear that fat accumulation in the liver, per se, is not a benign condition (3). Indeed, it is frequently associated with type 2 diabetes in both adults and children (4,5) and has been labeled as the hepatic component of the metabolic syndrome (2,3).Worsening of the dyslipidemic profile has been described in adults in association with insulin resistance and type 2 diabetes (6 -8). Garvey et al. (7) have shown that subjects with type 2 diabetes have larger VLDL and smaller LDL and HDL particles compared with insulinsensitive subjects. The insulin-resistant and type 2 diabetic groups also had greater concentrations of these atherogenic particles. Further studies by Toledo et al. (8) reported that the presence of hepatic steatosis in obese subjects with type 2 diabetes further altered lipoprotein composition compared with type 2 diabetic subjects without fatty liver. Type 2 diabetic subjects with fatty liver had larger triglyceride-rich VLDL particles, smaller LDL and HDL particles, and reduced concentrations o...

We previously evaluated the responses to dietary cholesterol in children and young adults. In this study, the effects of dietary cholesterol on plasma lipids and LDL atherogenicity were evaluated in 42 elderly subjects (29 postmenopausal women and 13 men > 60 y old). Our exclusion criteria were diabetes, heart disease, and the use of reductase inhibitors. The study followed a randomized crossover design in which subjects were assigned to consume the equivalent of 3 large eggs (EGG) daily or the same amount of a cholesterol-free, fat-free egg substitute (SUB) for a 1-mo period. After a 3-wk washout period, subjects were assigned to the alternate treatment. The concentration of plasma cholesterol after the EGG period varied among subjects. When all subjects were evaluated, there were significant increases in LDL cholesterol (LDL-C) (P < 0.05) and HDL-C (P < 0.001) for both men and women during the EGG period, resulting in no alterations in the LDL-C:HDL-C or the total cholesterol:HDL-C ratios. In addition, the LDL peak diameter was increased during the EGG period for all subjects. In contrast, the measured parameters of LDL oxidation, conjugated diene formation, and LDL lag time did not differ between the EGG and the SUB periods. We conclude from this study that dietary cholesterol provided by eggs does not increase the risk for heart disease in a healthy elderly population.

Female ovariectomized guinea pigs, a model for menopausal women, were fed either a control diet or a diet containing 10 g/100 g of a lyophilized grape preparation for 12 wk. The macronutrient composition of the grape preparation was: simple carbohydrates, 90 g/100 g; protein, 4 g/100 g; and dietary fiber, 6 g/100 g. Control and grape diets had the same composition except for the percentage of macronutrients provided by the grape preparation. Polyphenols were present in the grape preparation at 0.58 g/100 g and included flavans, anthocyanins, quercetin, myricetin, kaempferol and resveratrol. Dietary cholesterol was 0.33 g/100 g to raise plasma cholesterol concentrations and ensure the development of atherosclerosis. Plasma LDL cholesterol concentrations did not differ between groups, whereas plasma triglycerides and VLDL cholesterol were 39 and 50% lower, respectively in guinea pigs fed the grape diet compared with controls (P < 0.05). Significant modifications in LDL particles included 58 and 30% lower triglycerides and phospholipids, respectively (P < 0.0001). Hepatic acyl CoA:cholesteryl acyltransferase activity was 27% lower (P < 0.05) in the grape diet-fed group compared with controls. In addition, concentrations of cholesterol in the aorta were 33% lower (P < 0.05) in guinea pigs fed the grape diet. These results suggest that grape intake in ovariectomized guinea pigs alters hepatic cholesterol metabolism, which may affect VLDL secretion rates and result in less accumulation of cholesterol in the aorta.

Waist circumference (WC) has been postulated to have stronger associations with biomarkers of coronary heart disease (CHD) than BMI. In this study, we measured the level of activity by determining steps walked per day and select biomarkers for CHD risk in 80 overweight or obese (BMI = 25-37 kg/m(2)) premenopausal women to evaluate whether these biomarkers are associated with WC or BMI. The plasma biomarkers measured, using samples from women who had fasted for 12 h, were lipids, apolipoproteins (apo), LDL peak diameter, LDL susceptibility to oxidation, glucose, leptin, and insulin. We identified subjects with the metabolic syndrome (11%) and insulin resistance (30%) to further distinguish subjects at increased risk for CHD. Both BMI and WC were positively correlated with insulin (r = 0.376 and 0.384, respectively, P < 0.05) and leptin (r = 0.614 and 0.512, respectively, P < 0.01) and negatively correlated with the number of steps taken per day (r = -0.245 and -0.354, respectively, P < 0.05). In addition, WC had positive correlations with diastolic blood pressure (r = 0.250, P < 0.05), plasma triglycerides (TG) (r = 0.270, P < 0.05), and apo C-III (r = 0.240, P < 0.05). Women with BMI > or = 30 kg/m(2) or WC > 88 cm had significantly higher leptin concentrations than women having a BMI < 30 kg/m(2) or a WC < or = 88 cm; women with WC > 88 cm also had higher diastolic pressure (P < 0.05), and higher plasma TG (P < 0.05) and apo C-III (P < 0.05) concentrations than those with WC < or = 88. In addition, subjects with the higher WC walked an average of 1000 fewer steps per day (P < 0.01). These results suggest that WC is a stronger predictor of CHD risk than BMI and is more closely associated with the level of exercise in premenopausal women.