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Changes in plasma lipid and apolipoprotein profiles were evaluated in 12 healthy, unfit subjects (VO(2peak) 39.1+/-2.8 ml.kg(-1).min(-1); 5 women, 7 men) at baseline and following endurance exercise training. The exercise protocol consisted of a 6-week endurance exercise training program (4-5 days week(-1); 60 min.session(-1); > or =65% HR(max)). Subjects were randomly assigned to consume an egg- (n=6; 12 eggs.week(-1)) or no-egg (n=6; 0 eggs.week(-1))-based, eucaloric, standardized diet for 8 weeks. Both diets were macronutrient balanced [60% carbohydrate, 30% fat, 10% protein (0.8 g.kg(-1).day(-1))] and individually designed for weight maintenance. Plasma lipids were measured twice within the same week at baseline and following exercise training. At baseline, subjects were normolipidemic with values of 163.9+/-41.8, 84.8+/-36.7, 60.6+/-15.4 and 93.1+/-52 mg dl(-1) for total cholesterol, LDL cholesterol and HDL cholesterol and triglyceride concentrations, respectively. A two-way ANOVA was used to analyze diet and exercise effects and interactions. In both groups, endurance exercise training resulted in a significant 10% increase in HDL-C (P

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 > or RESULTS—Overall, the high-HFF group had 88% higher concentrations of large VLDL compared with the low-HFF group (P < 0.001). Likewise, the high-HFF group had significantly higher concentrations of small dense LDL (P < 0.007); however, the low-HFF group had significantly higher concentrations of large HDL (P < 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 < 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.

Carbohydrate-restricted diets (CRDs) promote weight loss, reductions in plasma triacylglycerol (TAG) levels, and increases in high-density lipoprotein cholesterol (HDL-C) levels but may cause undesirable low-density lipoprotein cholesterol (LDL-C) responses in some people. The objective of the present study was to determine the effect of adding soluble fiber to a CRD on plasma LDL-C and other traditionally measured markers of cardiovascular disease. Using a parallel-arm, double-blind, placebo-controlled design, 30 overweight and obese men (body mass index, 25-35 kg/m(2)) were randomly assigned to supplement a CRD with soluble fiber (Konjac-mannan, 3g/d) (n = 15) or placebo (n = 15). Plasma lipids, anthropometrics, body composition, blood pressure, and nutrient intake were evaluated at baseline and at 6 and 12 weeks. Compliance was excellent as assessed by 7-day weighed dietary records and ketonuria. Both groups experienced decreases in (P < .01) body weight, percent body fat, systolic blood pressure, waist circumference, and plasma glucose levels. After 12 weeks, HDL-C and TAG improved significantly in the fiber (10% and -34%) and placebo (14%, -43%) groups. LDL-C decreased by 17.6% (P < .01) at week 6 and 14.1% (P < .01) at week 12 in the fiber group. Conversely, LDL-C reductions were significant in the placebo group only after 12 weeks (-6.0%, P < .05). We conclude that although clearly effective at lowering LDL-C, adding soluble fiber to a CRD during active and significant weight loss provides no additional benefits to the diet alone. Furthermore, a CRD led to clinically important positive alterations in cardiovascular disease risk factors.

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.

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.

The associations between macronutrient intake and plasma parameters associated with increased risk for coronary heart disease (CHD) were evaluated in 80 overweight premenopausal women. We hypothesized that higher carbohydrate intake would be associated with a more detrimental plasma lipid profile. Dietary data were collected using a validated food frequency questionnaire (FFQ). Plasma total cholesterol (TC), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were determined from two fasting blood samples. In addition, selected apolipoproteins (apo) and LDL peak size were measured. Values for TC, TG and HDL were not in the range of risk classification; however, the mean values of LDL-C, 2.7 +/- 0.7 mmol/L, were higher than the current recommendations. Carbohydrate intake was positively associated with TG and apo C-III (P.01) concentrations, and negatively associated with LDL diameter (P.01). Participants were divided into low (53% of energy) or high (or = 53% energy) carbohydrate intake groups. Individuals in the53% carbohydrate group consumed more cholesterol and total fat, but also had higher intake of polyunsaturated and monounsaturated fatty acids (SFAs). In contrast, subjects in theor =53% group consumed higher concentrations of glucose and fructose than those in the low-carbohydrate (LC) group. In addition, subjects consuming53% carbohydrate had lower concentrations of LDL-C and apo B (P.01) and a larger LDL diameter (P.05) than theor =53% group. These results suggest that the lower LDL-C in the LC group may be related to both the amount of carbohydrate and the type of fatty acids consumed by these subjects.

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, P0.05) and leptin (r = 0.614 and 0.512, respectively, P0.01) and negatively correlated with the number of steps taken per day (r = -0.245 and -0.354, respectively, P0.05). In addition, WC had positive correlations with diastolic blood pressure (r = 0.250, P0.05), plasma triglycerides (TG) (r = 0.270, P0.05), and apo C-III (r = 0.240, P0.05). Women with BMIor = 30 kg/m(2) or WC88 cm had significantly higher leptin concentrations than women having a BMI30 kg/m(2) or a WCor = 88 cm; women with WC88 cm also had higher diastolic pressure (P0.05), and higher plasma TG (P0.05) and apo C-III (P0.05) concentrations than those with WCor = 88. In addition, subjects with the higher WC walked an average of 1000 fewer steps per day (P0.01). 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.

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.

Psyllium, the husks from Plantago ovata (PO), is recognized as a potent agent in lowering plasma cholesterol. In this study, we tested the potential hypolipidemic effects of the seeds from PO and the mechanisms associated with the lowering of plasma lipids. Male Hartley guinea pigs (n = 30; 10 per group) were fed either a control diet or diets containing 7.5 or 10 g/100 g PO for 4 wk. Diets were identical in composition except for the fiber source. The control diet contained 10 g/100 g cellulose and 2.5 g/100 g guar gum, whereas the PO diets were adjusted to a total of 12.5 g/100 g fiber with cellulose. Although a dose response was not observed, plasma triglycerides and LDL cholesterol were 34 and 23% lower in the PO groups compared with the control (P < 0.01). Lecithin cholesterol acyltransferase (LCAT) and cholesterol ester transfer protein (CETP) activities were significantly affected by the PO diets. The control group had 100 and 36% higher LCAT and CETP (P < 0.01) activities, respectively, compared with the PO groups. Hepatic total and free cholesterol concentrations were not affected by PO, but cholesteryl ester concentrations were 50% (P < 0.01) lower in the PO groups compared with the control. The activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-limiting enzyme of cholesterol synthesis was up-regulated in the PO groups by 37%. Similarly, the activity of cholesterol 7alpha-hydroxylase, the regulatory enzyme of cholesterol catabolism to bile acids was 33% higher in the PO groups (P < 0.02). Fecal bile acids were 3 times higher in the PO groups than in the control group. These results suggest that PO exerts its hypolipidemic effect by affecting bile acid absorption and altering hepatic cholesterol metabolism.

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.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 (HFFor5.5%). Fasting lipoprotein subclasses were determined using nuclear magnetic resonance spectroscopy.Overall, the high-HFF group had 88% higher concentrations of large VLDL compared with the low-HFF group (P0.001). Likewise, the high-HFF group had significantly higher concentrations of small dense LDL (P0.007); however, the low-HFF group had significantly higher concentrations of large HDL (P0.001). Stepwise multiple regression analysis revealed that high HFF was the strongest single correlate, accounting for 32.6% of the variance in large VLDL concentrations (P0.002).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.

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 (1)H 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 cm(2) [34.6, 49.6]) and was similar in Caucasians (65.2 cm(2) [55.9, 76.0]) and Hispanics (70.5 cm(2) [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.

Context: Adiponectin levels are lower in obese children and adolescents, whereas markers of inflammation and proinflammatory cytokines are higher. Hypoadiponectinemia may contribute to the low-grade systemic chronic inflammatory state associated with childhood obesity.Objective: We investigated whether C-reactive protein (CRP), the prototype of inflammation, is related to adiponectin levels independently of insulin resistance and adiposity.Design, Setting, Participants, and Main Outcome Measures: In a multiethnic cohort of 589 obese children and adolescents, we administered a standard oral glucose tolerance test and obtained baseline measurements for adiponectin, plasma lipid profile, CRP, IL-6, and leptin.Results: Stratifying the cohort into quartiles of adiponectin levels and adjusting for potential confounding variables, such as age, gender, ethnicity, body mass index z-score, pubertal status, and insulin sensitivity, the present study revealed that low levels of adiponectin are associated not only with higher CRP levels, but also with components of the metabolic syndrome, such as low high-density lipoprotein cholesterol and a high triglyceride-to-high-density-lipoprotein ratio.Conclusions: 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.

To determine the effects of a weight loss program, including dietary modifications, increased physical activity and dietary supplement (L-carnitine or placebo) on anthropometrics, leptin, insulin, the metabolic syndrome (MS) and insulin resistance in overweight /obese premenopausal women.Participants consumed a hypocaloric diet; 30% protein, 30% fat and 40% carbohydrate in addition to increasing number of steps/day. Carnitine supplementation followed a randomized double blind protocol. Protocol lasted for 10 weeks. Seventy subjects (35 in the control and 35 in the carnitine group) completed the intervention. Anthropometrics, plasma insulin and leptin concentrations and body composition were measured. The number of subjects with the MetSyn and insulin resistance, were assessed at baseline and post-intervention.Because there were no significant differences between the carnitine and the placebo groups for all measured parameters, participants were grouped together for all analysis. Subjects decreased total energy (-26.6%, p0.01) and energy from carbohydrate (-17.3%, p0.01) and increased energy from protein by 67% (p0.01) and number of steps/day (42.6%, p0.01). Body weight (-4.6%, p0.001), body mass index (-4.5%, p0.01), waist circumference (-6.5%, p0.01), total fat mass (-1.7%, p0.01), trunk fat mass (-2.0%, p0.01), insulin (- 17.9%, p0.01) and leptin (-5.9%, p0.05) decreased after the intervention. Ten of 19 participants with insulin resistance became insulin sensitive and 7 of 8 participants with the MetSyn no longer had the syndrome after the intervention.Moderate increases in physical activity and a hypocaloric/high protein diet resulted in multiple beneficial effects on body anthropometrics and insulin sensitivity. Realistic dietary and physical activity goals must be the focus of intervention strategies for overweight and obese individuals.

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.

Background Microsomal transfer protein inhibitors (MTPi) have the potential to be used as a drug to lower plasma lipids, mainly plasma triglycerides (TG). However, studies with animal models have indicated that MTPi treatment results in the accumulation of hepatic TG. The purpose of this study was to evaluate whether JTT-130, a unique MTPi, targeted to the intestine, would effectively reduce plasma lipids without inducing a fatty liver. Methods Male guinea pigs (n = 10 per group) were used for this experiment. Initially all guinea pigs were fed a hypercholesterolemic diet containing 0.08 g/100 g dietary cholesterol for 3 wk. After this period, animals were randomly assigned to diets containing 0 (control), 0.0005 or 0.0015 g/100 g of MTPi for 4 wk. A diet containing 0.05 g/100 g of atorvastatin, an HMG-CoA reductase inhibitor was used as the positive control. At the end of the 7th week, guinea pigs were sacrificed to assess drug effects on plasma and hepatic lipids, composition of LDL and VLDL, hepatic cholesterol and lipoprotein metabolism. Results Plasma LDL cholesterol and TG were 25 and 30% lower in guinea pigs treated with MTPi compared to controls (P < 0.05). Atorvastatin had the most pronounced hypolipidemic effects with a 35% reduction in LDL cholesterol and 40% reduction in TG. JTT-130 did not induce hepatic lipid accumulation compared to controls. Cholesteryl ester transfer protein (CETP) activity was reduced in a dose dependent manner by increasing doses of MTPi and guinea pigs treated with atorvastatin had the lowest CETP activity (P < 0.01). In addition the number of molecules of cholesteryl ester in LDL and LDL diameter were lower in guinea pigs treated with atorvastatin. In contrast, hepatic enzymes involved in maintaining cholesterol homeostasis were not affected by drug treatment. Conclusion These results suggest that JTT-130 could have potential clinical applications due to its plasma lipid lowering effects with no alterations in hepatic lipid concentrations.