Strenuous physical exercise accelerates the lipid peroxide clearing transport by HDL.

PURPOSE: Physical exercise has cardioprotective functions, which have been partly linked to high-density lipoprotein (HDL), and its functions. We studied the effects of endogenous oxidative stress, induced by acute exhaustive physical exercise, on concentration of oxidized HDL lipids. METHODS: Twenty-four male national top-level endurance runners, 12 middle-distance runners and 12 marathon runners performed a maximal run on a treadmill until exhaustion. We analyzed concentrations of oxidized HDL (oxHDLlipids) and LDL lipids (oxLDLlipids), serum antioxidant potential (TRAP), paraoxonase activity and malondialdehyde. Venous blood samples were taken before, immediately, 15 and 90 min after exercise. RESULTS: Immediately after the treadmill run the concentration of oxHDLlipids was increased by 24 % (p < 0.01). Simultaneously, the ratio of oxHDLlipids to oxLDLlipids increased by 55 % and the oxLDLlipids levels decreased by 19 % (p < 0.001), while serum malondialdehyde and TRAP increased by 54 % (p < 0.001) and 29 % (p < 0.01), respectively. After the 90 min recovery the concentration of oxHDLlipids was decreased towards the pre-exercise level, but that of oxLDLlipids remained decreased below pre-exercise values (p < 0.001). The change in oxLDLlipids after the run correlated positively with VO2max (r = 0.67, p < 0.001) and negatively with the change in paraoxonase activity (r = -0.47, p < 0.05). CONCLUSIONS: We conclude that acute exhaustive physical exercise increased the concentration of oxHDLlipids and decreased that of oxLDLlipids and the ratio of oxLDLlipids to oxHDLlipids, which suggests that during physical exercise HDL has an active role in the removal of lipid peroxides.

Postprandial triglyceride response in normolipidemic, hyperlipidemic and obese subjects - the influence of polydextrose, a non-digestible carbohydrate.

BACKGROUND: Three independent trials were conducted to evaluate postprandial triglyceride (TG) responses in subjects with different lipid metabolism. The effect of polydextrose (PDX), a soluble non-digestible carbohydrate, on postprandial response was also studied using practically relevant, high fat meal interventions. METHODS: A total of 19 normolipidemic (average BMI 24.1 kg/m(2)), 21 overweight/hyperlipidemic (average BMI 29.6 kg/m(2)) and 18 obese/non-diabetic subjects (average BMI 33.6 kg/m(2)) were included in the study. On two separate occasions all subjects ate two high-fat meals (4293 kJ, 36% from fat), one with PDX (either 12.5 g or 15 g) and one without PDX during placebo-controlled, double-blind, crossover and randomized trials. To obtain the triglyceride measurements venous blood samples were taken before the consumption of the test meal and five times afterwards, up to 6 h post-test meal. The triglyceride responses were modeled using a mixed-effects linear model. RESULTS: The key variables that explain the variation of the postprandial triglyceride response in the different subject groups were: baseline triglyceride concentration, time point, and PDX vs. placebo treatment (p < 0.05). The maximum postprandial TG concentration was more pronounced in hyperlipidemic group compared to normolipidemic (p < 0.001) or obese groups (p < 0.01). The modeled TG response analysis showed that irrespective of the study population PDX supplementation was one of the factors significantly reducing triglyceride response compared to the placebo treatment (p < 0.05). CONCLUSIONS: Subjects with elevated fasting triglyceride levels display exaggerated and prolonged postprandial triglyceride responses. PDX, a soluble non-digestible carbohydrate, may offer a dietary concept for reducing the postprandial triglyceride response after the consumption of a meal containing a high concentration of fat.

Lipid Oxidation Products and the Risk of Cardiovascular Diseases: Role of Lipoprotein Transport.

Cholesterol has for decades ruled the history of atherosclerotic cardiovascular diseases (CVDs), and the present view of the etiology of the disease is based on the transport of cholesterol by plasma lipoproteins. The new knowledge of the lipoprotein-specific transport of lipid oxidation products (LOPs) has introduced another direction to the research of CVD, revealing strong associations between lipoprotein transport functions, atherogenic LOP, and CVD. The aim of this review is to present the evidence of the lipoprotein-specific transport of LOP and to evaluate the potential consequences of the proposed role of the LOP transport as a risk factor. The associations of cholesterol and lipoprotein LOP with the known risk factors of CVD are mostly parallel, and because of the common transport and cellular intake mechanisms it is difficult to ascertain the independent effects of either cholesterol or LOP. While cholesterol is known to have important physiological functions, LOPs are merely regarded as metabolic residues and able to initiate and boost atherogenic processes. It is therefore likely that with the increased knowledge of the lipoprotein-specific transport of LOP, the role of cholesterol as a risk factor of CVD will be challenged.

Circulating oxidised LDL lipids, when proportioned to HDL-c, emerged as a risk factor of all-cause mortality in a population-based survival study.

BACKGROUND AND OBJECTIVE: the data concerning the predictive role of oxidised LDL (ox-LDL) in all-cause mortality are scarce. We investigated whether circulating ox-LDL would stand out as a risk factor of total mortality in the elderly. Study subjects, design and methods: a total of 1,260 elderly inhabitants (533 men, 727 women) aged 64 years or more from Lieto, South-Western Finland participated the study in 1998-99. Medical records were re-examined approximately a decade later in January 2009. Circulating ox-LDL lipids were used as the main outcome measure. The comparisons were obtained by the Cox hazard ratio model. RESULTS: during the 10-year follow-up, 467 participants had died (37%), of whom 36% had died of atherosclerotic cardiovascular diseases. Ox-LDL was a significant predictor of all-cause mortality, when proportioned to low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c) or apolipoprotein A1 (apoA1). These findings were independent of age, sex, body mass index, smoking, blood pressure and diabetes (P < 0.05 for all). CONCLUSION: circulating ox-LDL lipids, when proportioned to LDL-c, HDL-c or apoaA1, stand out as a risk factor for all-cause mortality independent of major confounding attributes. In the prospective survival and increasing disease burden caused by accumulating age, oxidative stress may have a considerable role.

Young men with poor cardiorespiratory fitness combined with lower testosterone have high levels of oxidized LDL lipids--being fit alters this relationship.

PURPOSE: We hypothesized that lower androgen status together with poor physical fitness associates with atherogenic lipid profile and oxidative stress. METHODS: Volunteered young men (N = 846, mean age 25.1 ± 4.6 years) were categorized into unfit, average fit, and fit groups according to tertiles of maximal oxygen uptake, series of muscle endurance tests, and maximal upper and lower body strength. Furthermore, concentrations of serum testosterone (TT) and free testosterone (FT) were determined to divide participants into lower and higher testosterone (loTT, hiTT) and free testosterone (loFT, hiFT) subgroups, using medians as cut-off points. The participants were divided into subgroups according to Fitness × Testosterone (Unfit/Average Fit/ Fit × Low/High TT/FT), and the concentrations of serum lipids and ox-LDL were measured. RESULTS: The loTT/unfit cardiorespiratory subgroup had 29% higher concentration of ox-LDL compared with the loTT/fit cardiorespiratory subgroup (p = .044). The loTT / unfit cardiorespiratory subgroup had a significantly higher ratio of ox-LDL/HDL-cholesterol compared with the other five TT subgroups (p < .05, in all). While ox-LDL showed a gradual form of decrease from unfit to fit in loTT cardiorespiratory subgroups, no differences were seen in muscular fitness or maximal strength (upper and lower body) subgroups. CONCLUSIONS: Young men with poor cardiorespiratory fitness together with lower levels of TT have higher concentrations of ox-LDL. Good cardiorespiratory fitness combined with lower androgen levels is not related to atherogenic lipid profile. The combination of poor muscular fitness, or maximal muscle strength, and lower TT levels does not cause atherogenic lipid profile.

Liver and pancreatic fat content and metabolism in healthy monozygotic twins with discordant physical activity.

BACKGROUND & AIMS: Ectopic fat in muscle and liver is linked to obesity and type 2 diabetes. Recently, pancreatic lipid accumulation has also been associated with ß-cell dysfunction and reduced insulin production, leading to the development of type 2 diabetes. Physical exercise training has been shown to attenuate ß-cell dysfunction in patients, but little is known about its effects on pancreatic and hepatic fat accumulation. In this study, we validated in-vivo proton magnetic resonance spectroscopy ((1)H MRS) in pancreatic fat measurement with biochemical measurements in a pig model. Thereafter, the effects of increased physical activity on the amounts of pancreatic and liver fat were studied in eight monozygotic twin pairs who have discordant physical activity and fitness. METHODS: Pancreatic fat content was studied in 15 pigs using (1)H MRS and/or biochemical analyses. In addition, liver and pancreatic fat were assessed using (1)H MRS in eight monozygotic male twin pairs with 18% mean difference in VO(2max) between the twin brothers. RESULTS: Twins with higher physical fitness had 23% less liver fat (1.3±1.3% vs. 2.1±2.6%, p=0.022) but no such difference was observed in the pancreatic fat (8.2±9.3% vs. 9.8±8.5%, respectively, p=0.3). Hepatic fat content was inversely associated with VO(2max). A positive association was found between pancreatic and liver fat contents (ß=5.18, p=0.012). Pancreatic fat content was also associated with insulin sensitivity indexes and plasma adiponectin and glutamyltransferase concentrations. CONCLUSIONS: Pancreatic fat content is associated with insulin resistance and hepatic fat content. An active lifestyle seems to beneficially influence hepatic fat metabolism.

The associations of oxidized lipoprotein lipids with lipoprotein subclass particle concentrations and their lipid compositions. The Cardiovascular Risk in Young Finns Study.

OBJECTIVE: Oxidation of low-density lipoprotein (LDL) may promote atherosclerosis, whereas the reverse transport of oxidized lipids by high-density lipoprotein (HDL) may contribute to atheroprotection. To provide insights into the associations of lipoprotein lipid oxidation markers with lipoprotein subclasses at the population level, we investigated the associations of oxidized HDL lipids (oxHDLlipids) and oxidized LDL lipids (oxLDLlipids) with lipoprotein subclasses in a population-based cross-sectional study of 1395 Finnish adults ages 24-39 years. METHODS: The analysis of oxidized lipids was based on the determination of the baseline level of conjugated dienes in lipoprotein lipids. A high-throughput nuclear magnetic resonance (NMR) platform was used to quantify circulating lipoprotein subclass concentrations and analyze their lipid compositions. RESULTS: OxHDLlipids were mainly not associated with lipoprotein subclass lipid concentrations and lipid composition after adjustment for Apolipoprotein-A1 (Apo-A1), waist circumference and age. OxLDLlipids were associated with several markers of lipoprotein subclass lipid concentrations and composition after adjustment for Apolipoprotein-B (Apo-B), age and waist circumference. Several measures of HDL and LDL subclasses, including phospholipid and triglyceride composition, associated directly with oxLDLlipids. Cholesterol ester and free cholesterol composition in HDL and LDL associated inversely with oxLDLlipids. CONCLUSION: We conclude that these results do not support the idea that HDL's particle size or composition would reflect its functional capacity in the reverse transport of oxidized lipids. On the contrary, oxLDLlipids were associated with the entire lipoprotein subclass profile, including numerous associations with the compositional descriptors of the particles. This is in line with the suggested role of LDL oxidation in atherogenesis.

Oxidative stress in non-small cell lung cancer: role of nicotinamide adenine dinucleotide phosphate oxidase and glutathione.

BACKGROUND: Cigarette smoke is strongly associated with NSCLC, but the carcinogenesis of NSCLC is poorly understood. METHODS: To discover the role of oxidative stress and anti-oxidative defense in NSCLC, we measured NADPH oxidase (NOX) activity, myeloperoxidase activity, 8-OHdG, and glutathione content from lung specimens. These came from 32 patients: 22 NSCLC patients and ten controls without cancer. RESULTS: In NSCLC patients, NOX activity was significantly higher both in the malignant (p = 0.001) and non-malignant (p = 0.044) samples from NSCLC patients, than in the control specimens. Myeloperoxidase activity was lower (p = 0.001) and glutathione content (p = 0.009) higher in malignant tissue. No significant difference was observable in 8-OHdG content between patient groups. CONCLUSIONS: Increase in NOX activity in the malignant tissues was independent of smoking history and myeloperoxidase activity, suggesting its independent role in NSCLC pathogenesis.

Oxidized lipoprotein lipids and atherosclerosis.

Plasma lipoproteins contain variable amounts of lipid oxidation products (LOP), which are known to impair normal physiological functions and stimulate atherosclerotic processes. Recent evidence indicates that plasma lipoproteins are active carriers of LOP, low-density lipoprotein (LDL) directing transport toward peripheral tissues, and high-density lipoprotein (HDL) being active in the reverse transport. It has been proposed that the lipoprotein-specific transport of LOP could play a role in atherosclerosis-related effects of LDL and HDL. This article gives an overview of the present knowledge of lipoprotein LOP transport and its association with the risk of atherosclerosis and cardiovascular diseases (CVD). Evidence of the significance of lipoprotein LOP transport comes mainly from studies of physiological oxidative stress and is supported by studies of the functionality apolipoprotein A-1 mimetic peptides. A large body of data has accumulated indicating that lipoprotein LOP transport is connected to the risk of atherosclerosis. While high levels of LOP carried by LDL are indicative of elevated risk, high LOP level in HDL appears to associate with protection. If confirmed, the proposed lipoprotein LOP transport function would affect conception of the etiology of atherosclerosis, but would not conflict current views of the pathophysiological mechanisms. It could open new perspectives, such as the dietary origin of LOP, and the protective function of HDL in clearance of LOP. Focusing on LOP could give additional tools especially for prevention and diagnosis, but would not radically change the management of atherosclerosis and CVD.

The metabolic syndrome in mice overexpressing neuropeptide Y in noradrenergic neurons.

A gain-of-function polymorphism in human neuropeptide Y (NPY) gene (rs16139) associates with metabolic disorders and earlier onset of type 2 diabetes (T2D). Similarly, mice overexpressing NPY in noradrenergic neurons (OE-NPYDBH) display obesity and impaired glucose metabolism. In this study, the metabolic syndrome-like phenotype was characterized and mechanisms of impaired hepatic fatty acid, cholesterol and glucose metabolism in pre-obese (2-month-old) and obese (4-7-month-old) OE-NPYDBH mice were elucidated. Susceptibility to T2D was assessed by subjecting mice to high caloric diet combined with low-dose streptozotocin. Contribution of hepatic Y1-receptor to the phenotype was studied using chronic treatment with an Y1-receptor antagonist, BIBO3304. Obese OE-NPYDBH mice displayed hepatosteatosis and hypercholesterolemia preceded by decreased fatty acid oxidation and accelerated cholesterol synthesis. Hyperinsulinemia in early obese state inhibited pyruvate- and glucose-induced hyperglycemia, and deterioration of glucose metabolism of OE-NPYDBH mice developed with aging. Furthermore, streptozotocin induced T2D only in OE-NPYDBH mice. Hepatic inflammation was not morphologically visible, but upregulated hepatic anti-inflammatory pathways and increased 8-isoprostane combined with increased serum resistin and decreased interleukin 10 pointed to increased NPY-induced oxidative stress that may predispose OE-NPYDBH mice to insulin resistance. Chronic treatment with BIBO3304 did not improve the metabolic status of OE-NPYDBH mice. Instead, downregulation of beta-1-adrenoceptors suggests indirect actions of NPY via inhibition of sympathetic nervous system. In conclusion, changes in hepatic fatty acid, cholesterol and glucose metabolism favoring energy storage contribute to the development of NPY-induced metabolic syndrome, and the effect is likely mediated by changes in sympathetic nervous system activity.

Two weeks of moderate-intensity continuous training, but not high-intensity interval training, increases insulin-stimulated intestinal glucose uptake.

Similar to muscles, the intestine is also insulin resistant in obese subjects and subjects with impaired glucose tolerance. Exercise training improves muscle insulin sensitivity, but its effects on intestinal metabolism are not known. We studied the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on intestinal glucose and free fatty acid uptake from circulation in humans. Twenty-eight healthy, middle-aged, sedentary men were randomized for 2 wk of HIIT or MICT. Intestinal insulin-stimulated glucose uptake and fasting free fatty acid uptake from circulation were measured using positron emission tomography and [18F]FDG and [18F]FTHA. In addition, effects of HIIT and MICT on intestinal GLUT2 and CD36 protein expression were studied in rats. Training improved aerobic capacity (P = 0.001) and whole body insulin sensitivity (P = 0.04), but not differently between HIIT and MICT. Insulin-stimulated glucose uptake increased only after the MICT in the colon (HIIT = 0%; MICT = 37%) (P = 0.02 for time × training) and tended to increase in the jejunum (HIIT = -4%; MICT = 13%) (P = 0.08 for time × training). Fasting free fatty acid uptake decreased in the duodenum in both groups (HIIT = -6%; MICT = -48%) (P = 0.001 time) and tended to decrease in the colon in the MICT group (HIIT = 0%; MICT = -38%) (P = 0.08 for time × training). In rats, both training groups had higher GLUT2 and CD36 expression compared with control animals. This study shows that already 2 wk of MICT enhances insulin-stimulated glucose uptake, while both training modes reduce fasting free fatty acid uptake in the intestine in healthy, middle-aged men, providing an additional mechanism by which exercise training can improve whole body metabolism.NEW & NOTEWORTHY This is the first study where the effects of exercise training on the intestinal substrate uptake have been investigated using the most advanced techniques available. We also show the importance of exercise intensity in inducing these changes.

Absorption of flavonols derived from sea buckthorn (Hippophaë rhamnoides L.) and their effect on emerging risk factors for cardiovascular disease in humans.

Sea buckthorn (Hippophaë rhamnoides L.) is a rich source of flavonols, especially isorhamnetin. Most prospective cohort studies have indicated some degree of inverse association between flavonoid intake and coronary heart disease. Animal and human studies suggest that sea buckthorn flavonoids may scavenge free radicals, lower blood viscosity, and enhance cardiac function. The effects of flavonol aglycones derived from sea buckthorn on the risk factors of cardiovascular disease as well as their absorption were studied in humans. The flavonols, ingested with oatmeal porridge, did not have a significant effect on the levels of oxidized low-density lipoprotein, C-reactive protein, and homocysteine, on the plasma antioxidant potential, or on the paraoxonase activity. Flavonols at two dosages in oatmeal porridge were rapidly absorbed, and a relatively small amount of sea buckthorn oil added to the porridge seemed to have increased the bioavailability of sea buckthorn flavonols consumed at the higher dose.

6-mo aerobic exercise intervention enhances the lipid peroxide transport function of HDL.

During acute exercise, the concentration of oxidized high-density lipoprotein (HDL) lipids (ox-HDL) is reported to increase suggesting that HDL may function in decreasing the concentration of oxidized low-density lipoprotein (LDL) lipids. However, the effect of exercise intervention on the lipid peroxide transport function of HDL is unknown. A randomized controlled trial with sedentary women (N = 161), aged 43-63, with no current use of hormone therapy, were randomized into a 6-month (mo) exercise group and a control group. During the 6-mo intervention, the concentration of ox-HDL increased in the exercise group by 5% and decreased in the control group by 2% (p = .003). Also, the ratio of ox-HDL to HDL-cholesterol increased by 5% in the exercise group and decreased by 1.5% in the control group (p = .036). The concentrations of cholesteryl ester transfer protein (CETP) and adiponectin did not change during the intervention. The concentration of serum triglycerides trended to decrease by 6% in the intervention group (p = .051). We found that the concentration of ox-HDL increased during the 6-mo aerobic exercise intervention, but the increase was not related to changes in the levels of CETP or adiponectin. These results, together with earlier studies, suggest that HDL has an active role in the reverse transport of lipid peroxides.

Increased Oxidative Stress in the Proximal Stomach of Patients with Barrett's Esophagus and Adenocarcinoma of the Esophagus and Esophagogastric Junction.

OBJECTIVES: Oxidative stress (OS) is an essential element in the pathogenesis of Barrett's esophagus (BE) and its transformation to adenocarcinoma (EAC). The state of OS in the proximal stomach of patients with BE and EAC is unknown. Isoprostanes are a specific marker of OS not previously used to determine OS from BE/EAC tissue samples. PATIENTS AND METHODS: OS was measured in 42 patients with BE (n = 9), EAC (n = 9), or both (n = 24) and 15 control patients. A STAT-8-Isoprostane EIA Kit served to identify 8-Isoprostanes (8-IP), and a Glutathione Assay Kit was used to measure glutathione reduced form (GSH) and glutathione oxidized form. An OxiSelect Oxidative DNA Damage ELISA Kit (8-OHdG) served to measure 8-OH-deoxyguanosine. RESULTS: The 8-IP (P = .039) and 8-OHdG (P = .008) levels were higher, and the GSH level lower (P = .031), in the proximal stomach of the study group than in that of the controls. Helicobacter pylori infection was present in 8% of the study patients. CONCLUSIONS: In the proximal stomach of BE and EAC patients, OS was elevated and antioxidative capacity was reduced. This finding suggests that the gastroesophageal reflux causing BE also induces oxidative stress in the proximal stomach and may contribute to the development of cancer in the proximal stomach and gastric cardia.

Longitudinal study of circulating oxidized LDL and HDL and fatty liver: the Cardiovascular Risk in Young Finns Study.

Oxidative reactions are thought to play a role in the inflammatory condition called fatty liver. It is unclear whether oxidized lipoprotein lipids or proteins are associated with future fatty liver. In the Cardiovascular Risk in Young Finns Study, we determined the circulating levels of LDL and HDL oxidized lipids and studied their associations with fatty liver assessed by ultrasonography. There were 1286 middle-aged subjects with normal liver and 288 subjects with fatty liver. Analysis of oxidized lipids consisted of conjugated dienes in isolated HDL (oxHDLlipids) and LDL (oxLDLlipids). Oxidized LDL was also measured with a method based on antibodies against oxidized apolipoprotein B (oxLDLprot). After adjustment for age, sex, leisure-time physical activity, body mass index, alcohol intake, smoking, serum LDL and HDL cholesterol as well as particle concentrations, participants with elevated oxLDLlipids (odds ratio for 1-SD change in oxLDLlipids = 1.27, p =0.011) had an increased risk for fatty liver. Similarly, a high oxidation score (oxLDLlipids + oxLDLprot) was directly associated with fatty liver (odds ratio=1.34, p = 0.012). The strongest direct association was seen with a high oxLDLlipids/oxHDLlipids ratio (odds ratio=1.49, p = 0.001). These data suggest that oxidized lipoprotein lipids are linked with the risk of fatty liver in middle-aged adults.

Effect of pravastatin on low-density lipoprotein oxidation and myocardial perfusion in young adults with type 1 diabetes.

OBJECTIVE: Diabetes has been associated with increased oxidative stress and impaired vascular function. Statins have been shown to reduce low-density lipoprotein (LDL) oxidizability and improve myocardial perfusion in hypercholesterolemic nondiabetic subjects. We studied whether pravastatin decreases LDL oxidation and improves myocardial perfusion in normocholesterolemic subjects with type 1 diabetes. METHODS AND RESULTS: In this randomized, double-blind study, myocardial perfusion was measured at rest and during dipyridamole stimulation with positron emission tomography and [15O]H2O during hyperinsulinemic euglycemia in 42 patients (age 30+/-6 years; LDL cholesterol 2.48+/-0.57 mmol/L) before and after 4-month treatment with pravastatin 40 mg/d or placebo. In addition, 12 healthy nondiabetic subjects were studied. LDL oxidation was measured by determining the level of baseline diene conjugation in lipids extracted from LDL. The level of LDL oxidation was similar in the pravastatin and placebo groups before treatment (23.9+/-4.6 versus 25.6+/-9.5 micromol/L, respectively) and decreased significantly during pravastatin treatment to 19.5+/-5.0 micromol/L (P<0.005). Myocardial perfusion reserve was significantly lower in diabetic patients compared with controls (4.15+/-1.29 versus 5.31+/-1.86, P<0.05) and did not change after treatment. Glycemic control and insulin sensitivity remained unchanged during treatment. CONCLUSIONS: Pravastatin treatment, resulting in decreased LDL oxidation, did not improve myocardial perfusion reserve in subjects with type 1 diabetes.

Weight reduction with very-low-caloric diet and endothelial function in overweight adults: role of plasma glucose.

OBJECTIVE: Obesity is associated with endothelial dysfunction that may contribute to the development of atherosclerosis. We studied whether weight reduction improves endothelial function in overweight individuals. METHODS AND RESULTS: Flow-mediated endothelium-dependent vasodilation of the brachial artery was measured in 67 adults (age: 46+/-7 years, body mass index: 35.2+/-5.4 kg/m2) before and after a 6-week weight reduction program induced by very-low-calorie diet (daily energy: 580 kcal/2.3 MJ). Caloric restriction reduced body weight from 101+/-18 to 90+/-17 kg. Flow-mediated vasodilation increased from 5.5%+/-3.7 to 8.8%+/-3.7% (P<0.0001). Nitrate-mediated vasodilation was not significantly affected. The improvement in flow-mediated dilation was associated with the reduction in plasma glucose concentration (P=0.0003). This relationship was independent of changes in weight, serum lipids, oxidized LDL, C-reactive protein, adiponectin, blood pressure, and insulin. CONCLUSIONS: Weight reduction with very-low-calorie diet improves flow-mediated vasodilation in obese individuals. This improvement is related to the reduction in plasma glucose concentration. These observations suggest that changes in glucose metabolism may determine endothelial vasodilatory function in obesity.

Triacylglycerol oxidation in pig lipoproteins after a diet rich in oxidized sunflower seed oil.

The effects of two sunflower seed oil diets differing in oxidation levels (PV in oils 1 and 190 mequiv O2/kg) on lipoprotein TAG and total lipid oxidation were investigated in growing pigs. For 2 wk, two groups of 10 pigs were fed either of the diets, after which blood samples were collected. A method based on RP-HPLC and electrospray ionization-MS was used for the analysis of oxidized TAG molecules in chylomicrons and VLDL. The baseline diene conjugation method was used for the estimation of in vivo levels of lipoprotein lipid oxidation. TAG molecules with a hydroxy, an epoxy, or a keto group attached to a FA, as well as TAG core aldehydes were detected in the samples. Typically, lipoprotein TAG and total lipids were more oxidized in the pigs fed on the oxidized oil compared with those fed on nonoxidized oil. Oxidation of dietary fat was thus reflected in the lipoprotein oxidation, which confirmed our earlier findings.

Triacylglycerol hydroperoxides not detected in pig small intestinal epithelial cells after a diet rich in oxidized triacylglycerols.

The presence of TAG hydroperoxides in the epithelial cells of the small intestines in growing pigs was studied after they had consumed a diet rich in either nonoxidized or oxidized sunflower seed oil (PV in oils, 1 and 190 mequiv O2/kg, respectively). To obtain molecular-level information on the oxidized TAG structures, a new approach based on TLC and HPLC-electrospray ionization-MS was used in the analysis of the samples. TAG hydroperoxides were not detected in the small intestinal mucosa or adipose tissue of either group, whereas TAG hydroxides, ketones, and epoxides were detected in all samples. The results suggest that dietary TAG hydroperoxides do not lead to the appearance of these molecules in the tissues.

Co-existence of insulin resistance and high concentrations of circulating oxidized LDL lipids.

INTRODUCTION: Insulin metabolism has been previously linked to oxidized low-density lipoproteins (ox-LDL), but corroborating intervention studies are lacking. We investigated whether changes in ox-LDL levels are accompanied by changes in insulin sensitivity in a 32-month life-style intervention study. MATERIALS AND METHODS: A 2-month weight reduction was followed by 6-month diet and exercise counselling and a 2-year follow-up period. Men of 35-50 years of age, BMI ≥ 30 kg/m(2), and waist circumference > 100 cm were recruited via newspapers in the city of Tampere, Finland. Of the 90 men meeting the inclusion criteria, 67 (76%) completed the study. Ox-LDL was estimated as the presence of oxidized lipids in LDL. Homeostasis model assessment of insulin resistance (HOMA-IR), ox-LDL, and ratio of ox-LDL and high-density lipoprotein cholesterol (ox-LDL/HDL-c) were used as the main outcome measures. RESULTS: The detected changes in HOMA-IR were strikingly similar to those in ox-LDL and ox-LDL/HDL-c. Compared to the first HOMA-IR quartile, the fourth quartile had 23%-51% higher concentrations in ox-LDL and ox-LDL/HDL-c at all time points (P < 0.05 for all). CONCLUSION: This weight reduction intervention study adds evidence to support the connection between insulin metabolism and oxidized LDL, possibly contributing to the higher incidence of atherosclerotic cardiovascular diseases among diabetic patients.