phytosterols and Obesity

Cardiovascular diseases associated with obesity are alarmingly increasing in both developed and developing countries. Obesity is mainly ascribed to higher lipid accumulation in the body. There are several simple approaches to treat this condition like lifestyle modification, dietary intervention, physical activities, drug treatment etc. There are many drugs available in the market to treat hyperlipidemia condition, but those drugs have many fatal adverse effects on human health. In view of this, it is reasonable to suggest some preventive measures by functional food ingredients as human health has acclimatized to these since thousands of years. Phytosterols have been studied since decades for its hypocholesterolemic effect in human nutrition. Although the mycosterols from fungi are still under- exploited, ergosterol and derivatives from fungal source have promising health beneficial effects in obesity associated cardiovascular diseases. This review aims to summarise the investigations on mycosterol with respect to obesity in the last decade and also scope of future research on its application in functional food supplements.

Topics: Dietary Supplements; Humans; Hyperlipidemias; Obesity; Phytosterols

Consumption of phytosterols (PSs), the plant-based analogs of cholesterol, can reduce serum cholesterol levels. This review discusses the current state of the art into the research of the structural features and dietary sources of PSs and their derivatives. The effect of PSs on individual lipid metabolites is summarized in the present review. PS-related nonalcoholic fatty liver disease (NAFLD), obesity, and the alleviation of inflammatory bowel diseases are discussed. PSs reduce the risk of having NAFLD by improving the blood biochemical parameters related to lipid transport and metabolism. However, current research on the circulating PSs indicates its safety concern regarding fatty liver disease induction. In addition, PS oxidation products exhibit pro-atherogenic properties, cytotoxicity oxidative stress, apoptosis, and pro-inflammatory properties. Further research is needed to investigate the bioavailability and safety issues of PSs and their derivatives in animal models and clinical trials.

Topics: Animals; Anticholesteremic Agents; Cholesterol; Diet; Humans; Inflammatory Bowel Diseases; Lipid Metabolism; Non-alcoholic Fatty Liver Disease; Obesity; Oxidation-Reduction; Phytosterols

Non-cholesterol sterols are validated biomarkers for intestinal cholesterol absorption and endogenous cholesterol synthesis. However, their use in metabolic disturbances has not been systematically explored. Therefore, we conducted a systematic review to provide an overview of non-cholesterol sterols as markers for cholesterol metabolism in different metabolic disorders. Potentially relevant studies were retrieved by a systematic search of three databases in July 2018 and ninety-four human studies were included. Cholesterol-standardized levels of campesterol, sitosterol and cholestanol were collected to reflect cholesterol absorption and those of lathosterol and desmosterol to reflect cholesterol synthesis. Their use as biomarkers was examined in the following metabolic disorders: overweight/obesity (

Topics: Biomarkers; Cardiovascular Diseases; Cholesterol; Desmosterol; Diabetes Mellitus; Humans; Intestinal Absorption; Intestinal Diseases; Kidney Diseases; Liver Diseases; Metabolic Diseases; Obesity; Overweight; Phytosterols; Sitosterols; Sterols

Among the 10 leading causes of death in developed countries are chronic non-communicable diseases (NCDs). The effect of these multifactorial diseases on public health has stimulated considerable research aimed at investigating their primary risk factors (genetic factors, stress, food intake, and amount of physical exercise). Thus, healthful foods (e.g., fruits, vegetables, oils, grains, and seeds) are sources of bioactive compounds that promote good health and disease prevention. Among their components are non-caloric substances identified as non-nutrients (polyphenols, phytosterols, saponins, and phytates), which have been found to have a role in modulating metabolic pathways, maintaining health, and preventing NCDs. The aim of this study is to demonstrate and review the performance of some non-nutrients, such as their antioxidant and anti-inflammatory action, modulation of the antiatherogenic lipid profile (higher high-density lipoprotein cholesterol, lower oxidized low-density lipoprotein, and triacylglycerols), reduction of glucose and fat intestinal absorption, increase in insulin sensitivity, and stimulation of nitic oxide synthesis.

Topics: Cardiovascular Diseases; Diabetes Mellitus; Diet; Humans; Noncommunicable Diseases; Obesity; Phytic Acid; Phytosterols; Polyphenols; Saponins

Overweight and obesity have a major impact on global health; their prevalence has rapidly increased in all industrialized countries in the past few decades and diabetes and hypertension are their direct consequences. Pharmacotherapy provides reinforcement for obesity treatment, but should be an adjunctive support to diet, exercise, and lifestyle modification. At present, only orlistat and sibutramine have been approved by the US Food and Drug Administration for long-term use, but sibutramine was withdrawn for sale by the European Medicines Agency. The development of functional foods for the prevention and/or treatment of obesity suppose an opportunity for the food market and involve the knowledge of the mechanisms of appetite and energy expenditure as well as the metabolic sensation of satiety. Strategies for weight control management affect gut hormones as potential targets for the appetite metabolic regulation, stimulation of energy expenditure (thermogenesis), and modifications in the metabolic activity of the gut microbiota. Functional foods for obesity may also include bioactive fatty acids, phenolic compounds, soybean, plant sterols, dietary calcium, and dietary fiber. This review intends to offer an overview of the present situation of the anti-obesity agents currently used in dietary therapy as well as some functional food ingredients with potentially anti-obesity effects.

Topics: Anti-Obesity Agents; Calcium, Dietary; Cyclobutanes; Diet; Dietary Fiber; Energy Metabolism; Exercise; Fatty Acids, Unsaturated; Food Analysis; Food Handling; Glycine max; Humans; Lactones; Life Style; Obesity; Orlistat; Phytosterols; Polyphenols; United States; United States Food and Drug Administration; Weight Loss

Increased blood cholesterol is an independent risk factor for atherosclerotic cardiovascular disease. Cholesterol homeostasis in the body is controlled mainly by endogenous synthesis, intestinal absorption, and hepatic excretion. Niemann-Pick C1-Like 1 (NPC1L1) is a polytopic transmembrane protein localized at the apical membrane of enterocytes and the canalicular membrane of hepatocytes. It functions as a sterol transporter to mediate intestinal cholesterol absorption and counter-balances hepatobiliary cholesterol excretion. NPC1L1 is the molecular target of ezetimibe, a potent cholesterol absorption inhibitor that is widely used in treating hypercholesterolemia. Recent findings suggest that NPC1L1 deficiency or ezetimibe treatment also prevents diet-induced hepatic steatosis and obesity in addition to reducing blood cholesterol. Future studies should focus on molecular mechanisms underlying NPC1L1-dependent cholesterol transport and elucidation of how a cholesterol transporter modulates the pathogenesis of metabolic diseases.

Topics: Animals; Anticholesteremic Agents; Atherosclerosis; Azetidines; Biliary Tract; Biological Transport; Carrier Proteins; Cholesterol; Endocytosis; Ezetimibe; Fatty Liver; Humans; Intestinal Absorption; Intestinal Mucosa; Intestines; Liver; Membrane Proteins; Membrane Transport Proteins; Mice; Obesity; Phytosterols; Primates

1. Dyslipoproteinaemia is a cardinal feature of the metabolic syndrome that accelerates atherosclerosis. It is characterized by high plasma concentrations of triglyceride-rich and apolipoprotein (apo) B-containing lipoproteins, with depressed concentrations of high-density lipoprotein (HDL). Dysregulation of lipoprotein metabolism in these subjects may be due to a combination of overproduction of very-low density lipoprotein (VLDL) apoB-100, decreased catabolism of apoB-containing particles and increased catabolism of HDL apoA-I particles. 2. Nutritional interventions may favourably alter lipoprotein transport in the metabolic syndrome. We review our collaborative studies, using stable isotopes and compartmental modelling, of the kinetic effects of fish oils, plant sterols (phytosterols) and weight reduction on the dyslipoproteinaemia in this disorder. 3. Fish oil supplementation diminished hepatic secretion of VLDL-apoB and enhanced conversion of VLDL to low-density lipoprotein (LDL)-apoB, without altering catabolism. 4. Plant sterols (phytosterols) did not have a significant effect on plasma concentrations of lipids and lipoprotein or the kinetics of apoB and apoA-I. 5. Modest weight reduction optimally decreased plasma triglyceride and LDL-cholesterol via reduction in hepatic apoB secretion and reciprocal upregulation of LDL catabolism. 6. The scope and potential of future studies using stable isotope tracers is discussed.

Topics: Biological Transport; Diet, Fat-Restricted; Fish Oils; Humans; Lipoproteins; Metabolic Syndrome; Models, Biological; Nutritional Physiological Phenomena; Obesity; Phytosterols; Radionuclide Imaging; Weight Loss

Sorghum is a rich source of various phytochemicals including tannins, phenolic acids, anthocyanins, phytosterols and policosanols. These phytochemicals have potential to significantly impact human health. Sorghum fractions possess high antioxidant activity in vitro relative to other cereals or fruits. These fractions may offer similar health benefits commonly associated with fruits. Available epidemiological evidence suggests that sorghum consumption reduces the risk of certain types of cancer in humans compared to other cereals. The high concentration of phytochemicals in sorghum may be partly responsible. Sorghums containing tannins are widely reported to reduce caloric availability and hence weight gain in animals. This property is potentially useful in helping reduce obesity in humans. Sorghum phytochemicals also promote cardiovascular health in animals. Such properties have not been reported in humans and require investigation, since cardiovascular disease is currently the leading killer in the developed world. This paper reviews available information on sorghum phytochemicals, how the information relates to current phytonutrient research and how it has potential to combat common nutrition-related diseases including cancer, cardiovascular disease and obesity.

Topics: Animals; Anthocyanins; Antioxidants; Cardiovascular Diseases; Edible Grain; Fatty Alcohols; Flavonoids; Fruit; Humans; Molecular Structure; Neoplasms; Obesity; Phenols; Phytosterols; Proanthocyanidins; Sorghum; Tannins

National guidelines indicate patients with elevated low- density lipoprotein cholesterol should consume less than 7% of calories from saturated fat and less than 200 mg of cholesterol. Trans fatty acids should also be limited. Incorporation of functional foods, such as stanol-containing margarine, soy products, and soluble fiber-rich cereals and vegetables can provide further benefit. In addition to weight loss and physical activity, individuals with hypertriglyceridemia benefit from a diet moderate in fat and carbohydrate rather than a low-fat diet. Including monounsaturated or omega-3 fatty acids lowers serum triglycerides. Many of the dietary strategies to optimize serum lipids also contribute to glycemic control in patients with diabetes mellitus.

Topics: Cholesterol, Dietary; Cholesterol, HDL; Cholesterol, LDL; Dietary Fats; Dietary Fiber; Energy Intake; Fatty Acids; Fatty Acids, Omega-3; Female; Humans; Hyperlipidemias; Male; Metabolic Syndrome; Obesity; Phytosterols; Soybean Proteins; Triglycerides

Cross-sectional studies have shown that obesity is associated with lower intestinal cholesterol absorption and higher endogenous cholesterol synthesis. These metabolic characteristics have also been observed in patients with type 2 diabetes, metabolic syndrome, steatosis or cholestasis. The number of intervention studies evaluating the effect of weight loss on these metabolic characteristics is, however, limited, while the role of the different fat compartments has not been studied into detail. In a randomized trial, abdominally obese men (N = 54) followed a 6-week very low caloric (VLCD) diet, followed by a 2 week weight-maintenance period. Non-cholesterol sterols were measured at baseline and after 8 weeks, and compared to levels in lean participants (N = 25). After weight loss, total cholesterol (TC)-standardized cholestanol levels increased by 0.18 µmol/mmol (p < 0.001), while those of campesterol and lathosterol decreased by 0.25 µmol/mmol (p < 0.05) and 0.39 µmol/mmol (p < 0.001), respectively. Moreover, after weight loss, TC-standardized lathosterol and cholestanol levels were comparable to those of lean men. Increases in TC-standardized cholestanol after weight loss were significantly associated with changes in waist circumference (p < 0.01), weight (p < 0.001), BMI (p < 0.001) and visceral fat (p < 0.01), but not with subcutaneous and intrahepatic lipids. In addition, cross-sectional analysis showed that visceral fat fully mediated the association between BMI and TC-standardized cholestanol levels. Intrahepatic lipid content was a partial mediator for the association between BMI and TC-standardized lathosterol levels. In conclusion, diet-induced weight loss decreased cholesterol synthesis and increased cholesterol absorption. The increase in TC-standardized cholestanol levels was not only related to weight loss, but also to a decrease in visceral fat volume. Whether these metabolic changes ameliorate other metabolic risk factors needs further study.

Topics: Biomarkers; Cholestanol; Cholesterol; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diet, Reducing; Humans; Male; Obesity; Phytosterols; Weight Loss

Increased physical activity is inversely related to the risk to develop cardiovascular disease (CVD). In a recent systematic review, it was reported that CVD patients had an increased cholesterol absorption and a decreased synthesis as compared with control participants. As increased physical activity levels reduce CVD risk, we hypothesized that exercise training will reduce cholesterol absorption and increase endogenous cholesterol synthesis in older overweight and obese men.. A randomized, controlled, crossover trial was performed. Seventeen apparently healthy older overweight and obese men were randomized to start with an aerobic exercise or no-exercise control period for 8 weeks, separated by 12 weeks washout. Fasting serum total cholesterol (TC) and non-cholesterol sterol concentrations were measured at baseline, and after 4 and 8 weeks.. The aerobic exercise program did not affect serum TC concentrations. In addition, exercise did not affect TC-standardized serum concentrations of sitosterol and cholestanol that are markers for cholesterol absorption. However, a trend for reduced TC-standardized campesterol concentrations, which is another validated marker for cholesterol absorption, was observed as compared with control. Lathosterol concentrations, reflecting cholesterol synthesis, did not differ between both periods.. Aerobic exercise training for 8 weeks did not lower serum TC concentrations in older overweight and obese men, but a trend towards a decrease in the cholesterol absorption marker campesterol was found. The cholesterol synthesis marker lathosterol did not change.. posted on www.clinicaltrials.gov as NCT03272061 on 7 September 2017.

Topics: Aged; Biomarkers; Body Mass Index; Cardiovascular Diseases; Cholesterol; Cross-Over Studies; Exercise; Exercise Therapy; Humans; Life Style; Male; Middle Aged; Obesity; Overweight; Phytosterols; Sterols; Surveys and Questionnaires

People who frequently consume whole grains show a lower incidence of arteriosclerotic disease than people who consume primarily refined grains. We examined whether or not rice bran extract containing the acylated steryl glucosides (ASG) fraction decreases blood LDL cholesterol levels in obese Japanese men with high blood levels of LDL cholesterol. The study utilized a randomized, double-blind design. A total of 51 subjects were randomly allocated to either a rice bran extract containing ASG fraction (RB-ASG) group or a placebo group. Subjects in the RB-ASG group received 30-50 mg/day of RB-ASG, and the placebo group took 9 capsules/day for 12 weeks. Before and after intake, height, weight, body fat percentage, systolic and diastolic blood pressure were measured, blood was collected, and visceral fat area, subcutaneous fat area, and abdominal circumference were determined based on umbilical computed tomography. Percentage decreases in blood LDL cholesterol, non-HDL cholesterol, LDL/HDL ratio, abdominal circumference and subcutaneous fat area were significantly better in the RB-ASG group than in the placebo group. These findings suggest that RB-ASG fraction may reduce blood LDL cholesterol levels and the risk of arteriosclerosis in obese Japanese men with high LDL cholesterol levels.

Topics: Asian People; Cholesterol, LDL; Double-Blind Method; Humans; Japan; Male; Middle Aged; Obesity; Oryza; Phytosterols

This study investigated the dietary effect of including pigmented rice bran with or without plant sterols on lipid profiles during energy restriction-induced weight loss in overweight and obese adults not taking cholesterol-lowering medication. In addition, the study examined the effect of intervention on biomarkers of oxidative stress and inflammation.. A group of 24 overweight and obese adults (age: 43 ± 6 years, body mass index 32 ± 1 kg/m(2), 18 females) were randomized to a 25% calorie-restricted diet containing either pigmented rice bran (RB) or the RB with addition of plant sterols (RB+PS) snack bars for 8 weeks. The individualized nutrient-balanced diet contained ∼70% of daily energy needs assessed from indirect calorimetry measured resting energy expenditure (EE) and physical activity-related EE assessed using accelerometry. Anthropometrics, blood pressure, blood lipids, glucose, urinary F2-isoprostanes, C-reactive protein, insulin, and leptin were measured at baseline and after 8 weeks of intervention.. Participants lost approximately 4.7 ± 2.2 kg (p < 0.001). Weight loss was not significant between the RB+PS and RB group (p = 0.056). Changes in body fat corresponded to changes in body weight. Average decrease in total cholesterol was significantly higher in the RB+PS group than in the RB group (difference 36 ± 25 g/dL vs 7 ± 16 g/dL; p = 0.044). A similar pattern was observed for the decrease in low-density lipoprotein (LDL) cholesterol (difference 22.3 ± 25.2 g/dL vs 4.4 ± 18.9 g/dL; p = 0.062). Changes in systolic blood pressure, serum levels of leptin, and F2-isoprostanes were significant between baseline values and after 8 weeks on the diet in both groups (p < 0.05) but did not differ between the 2 groups.. A nutrient-balanced and energy-restricted diet supplemented with rice bran and plant sterols resulted in a significant decrease in total and LDL cholesterol in overweight and obese adults.

Topics: Adult; Basal Metabolism; Blood Pressure; Body Composition; Body Mass Index; C-Reactive Protein; Caloric Restriction; Cholesterol, HDL; Cholesterol, LDL; Diet, Reducing; Dietary Fiber; Double-Blind Method; F2-Isoprostanes; Female; Humans; Insulin; Leptin; Male; Middle Aged; Motor Activity; Obesity; Overweight; Patient Compliance; Phytosterols; Triglycerides; Weight Loss; Young Adult

We examined serum cholesterol synthesis and absorption markers and their association with neonatal birth weight in obese pregnancies affected by gestational diabetes mellitus (GDM). Pregnant women at risk for GDM (BMI >30 kg/m²) were enrolled from maternity clinics in Finland. GDM was determined from the results of an oral glucose tolerance test. Serum samples were collected at six time-points, one in each trimester of pregnancy, and at 6 weeks, 6 months, and 12 months postpartum. Analysis of serum squalene and noncholesterol sterols by gas-liquid chromatography revealed that in subjects with GDM (n = 22), the serum Δ8-cholestenol concentration and lathosterol/sitosterol ratio were higher (P < 0.05) than in the controls (n = 30) in the first trimester, reflecting increased cholesterol synthesis. Also, subjects with GDM had an increased ratio of squalene to cholesterol (100 × μmol/mmol of cholesterol) in the second (11.5 ± 0.5 vs. 9.1 ± 0.5, P < 0.01) and third (12.1 ± 0.8 vs. 10.0 ± 0.7, P < 0.05) trimester. In GDM, the second trimester maternal serum squalene concentration correlated with neonatal birth weight (r = 0.70, P < 0.001). In conclusion, in obesity, GDM associated with elevated serum markers of cholesterol synthesis. Correlation of maternal serum squalene with neonatal birth weight suggests a potential contribution of maternal cholesterol synthesis to newborn weight in GDM.

Topics: Adult; Biomarkers; Birth Weight; Body Mass Index; Cholesterol; Diabetes, Gestational; Female; Fetal Macrosomia; Finland; Follow-Up Studies; Humans; Infant, Newborn; Male; Maternal Nutritional Physiological Phenomena; Obesity; Phytosterols; Postpartum Period; Pregnancy; Risk; Sitosterols; Squalene

Long-term dietary weight loss results in complex metabolic changes. However, its effect on cholesterol metabolism in obese subjects is still unclear.. We assessed the effects of 2 y of weight loss achieved with various diet regimens on phytosterols (markers of intestinal cholesterol absorption), lanosterol (marker of de novo cholesterol synthesis), and changes in apolipoprotein concentrations.. We conducted the 2-y Dietary Intervention Randomized Controlled Trial (DIRECT-a study of low-fat, Mediterranean, and low-carbohydrate diets). We assessed circulating phytosterol and lanosterol concentrations and their ratios to cholesterol and apolipoproteins A-I and B-100 in 90 DIRECT participants at 0, 6, and 24 mo.. We observed a significant upregulation of the markers of cholesterol absorption (campesterol: +16.8%, P < 0.001) and a downregulation of the markers of cholesterol synthesis (lanosterol: -16.5%, P = 0.008) during the active weight-loss phase (first 6 mo, weight loss of 5%, 6%, and 10% in the 3 diet groups, respectively), followed by a rebound (campesterol: -6.2%, P = 0.045; lanosterol: +43.7%, P < 0.001) during the next 18 mo (weight gain of 1%, 1%, and 2% in the 3 diet groups, respectively). HDL cholesterol continuously increased during the study (17.0%, P < 0.001), whereas LDL cholesterol remained constant. At the end of the 24-mo follow-up period, campesterol (P < 0.001) and lanosterol (P = 0.016) amounts were significantly higher than baseline values. The concentration of apolipoprotein B-100 correlated with cholesterol metabolism (ρ = 0.299 and P = 0.020 for lanosterol; ρ = -0.105 and NS for campesterol), and the homeostasis model assessment of insulin resistance correlated with lanosterol (ρ = 0.09, P = 0.001).. Long-term weight loss is related to a characteristic response suggestive of altered cholesterol and apolipoprotein metabolism. Various diets have a similar effect on these effects. DIRECT is registered at clinicaltrials.gov as NCT00160108.

Topics: Adult; Apolipoprotein A-I; Apolipoprotein B-100; Body Weight; Cholesterol; Diet, Reducing; Humans; Lanosterol; Male; Middle Aged; Obesity; Phytosterols; Statistics, Nonparametric; Weight Loss

The rise in LDL with egg feeding in lean insulin-sensitive (LIS) participants is 2- and 3-fold greater than in lean insulin-resistant (LIR) and obese insulin-resistant (OIR) participants, respectively.. We determined whether differences in cholesterol absorption, synthesis, or both could be responsible for these differences by measuring plasma sterols as indexes of cholesterol absorption and endogenous synthesis.. Plasma sterols were measured by gas chromatography-mass spectrometry in a random subset of 34 LIS, 37 LIR, and 37 OIR participants defined by the insulin sensitivity index (S(I)) and by BMI criteria selected from a parent group of 197 participants. Cholestanol and plant sterols provide a measure of cholesterol absorption, and lathosterol provides a measure of cholesterol synthesis.. The mean (±SD) ratio of plasma total absorption biomarker sterols to cholesterol was 4.48 ± 1.74 in LIS, 3.25 ± 1.06 in LIR, and 2.82 ± 1.08 in OIR participants. After adjustment for age and sex, the relations of the absorption sterol-cholesterol ratios were as follows: LIS > OIR (P < 0.001), LIS > LIR (P < 0.001), and LIR > OIR (P = 0.11). Lathosterol-cholesterol ratios were 0.71 ± 0.32 in the LIS participants, 0.95 ± 0.47 in the LIR participants, and 1.29 ± 0.55 in the OIR participants. After adjustment for age and sex, the relations of lathosterol-cholesterol ratios were as follows: LIS < OIR (P < 0.001), LIS < LIR (P = 0.03), and LIR < OIR (P = 0.002). Total sterol concentrations were positively associated with S(I) and negatively associated with obesity, whereas lathosterol correlations were the opposite.. Cholesterol absorption was highest in the LIS participants, whereas cholesterol synthesis was highest in the LIR and OIR participants. Therapeutic diets for hyperlipidemia should emphasize low-cholesterol diets in LIS persons and weight loss to improve S(I) and to decrease cholesterol overproduction in LIR and OIR persons.

Topics: Absorption; Cholesterol; Cross-Sectional Studies; Diet; Double-Blind Method; Eggs; Female; Gas Chromatography-Mass Spectrometry; Humans; Insulin Resistance; Linear Models; Male; Middle Aged; Obesity; Phytosterols; Sterols

To determine the effect on blood pressure of dietary advice to consume a combination of plant-based cholesterol-lowering foods (dietary portfolio).. For 1 year, 66 hyperlipidemic subjects were prescribed diets high in plant sterols (1.0 g/1000 kcal), soy protein (22.5 g/1000 kcal), viscous fibers (10 g/1000 kcal) and almonds (22.5 g/1000 kcal). There was no control group. Seven-day diet record, blood pressure and body weight were monitored initially monthly and later at 2-monthly intervals throughout the study.. Fifty subjects completed the 1-year study. When the last observation was carried forward for non-completers (n=9) or those who changed their blood pressure medications (n=7), a small mean reduction was seen in body weight 0.7+/-0.3 kg (P=0.036). The corresponding reductions from baseline in systolic and diastolic blood pressure at 1 year (n=66 subjects) were -4.2+/-1.3 mm Hg (P=0.002) and -2.3+/-0.7 mm Hg (P=0.001), respectively. Blood pressure reductions occurred within the first 2 weeks, with stable blood pressures 6 weeks before and 4 weeks after starting the diet. Diastolic blood pressure reduction was significantly related to weight change (r=0.30, n=50, P=0.036). Only compliance with almond intake advice related to blood pressure reduction (systolic: r=-0.34, n=50, P=0.017; diastolic: r=-0.29, n=50, P=0.041).. A dietary portfolio of plant-based cholesterol-lowering foods reduced blood pressure significantly, related to almond intake. The dietary portfolio approach of combining a range of cholesterol-lowering plant foods may benefit cardiovascular disease risk both by reducing serum lipids and also blood pressure.

Topics: Blood Pressure; Body Weight; Cholesterol; Cholesterol, Dietary; Diet Records; Dietary Fiber; Female; Humans; Hyperlipidemias; Hypertension; Male; Middle Aged; Obesity; Phytosterols; Prunus; Soybean Proteins; Weight Loss

Medium chain triacylglycerols (MCT) have been suggested as efficacious in weight management because they possess greater thermogenic qualities relative to long chain triacylglycerols; however, MCT may also increase circulating lipid concentrations, possibly increasing risk of cardiovascular disease (CVD). The present objective was to examine the effect of a diet supplemented with a functional oil (FctO) composed of energy expenditure-enhancing MCT (50% of fat), cholesterol-lowering phytosterols (22 mg/kg body weight), and triacylglycerol-suppressing n-3 fatty acids (5% of fat), versus a beef tallow-based diet (BT), on plasma lipid and aminothiol concentrations. In a randomized, single-blind, crossover design, partially-inpatient trial, 17 overweight women consumed each oil as part of a controlled, supervised, targeted energy balance diet for 27 days, with 4 or 8 weeks of washout between phases. Mean plasma total cholesterol concentration was lower (P <.0001), by 9.1%, on FctO (4.37 +/- 0.20 mmol/L) versus BT (4.80 +/- 0.20 mmol/L). Mean plasma low-density lipoprotein (LDL) cholesterol was also lower (P <.0001) following FctO (2.39 +/- 0.15 mmol/L) versus BT (2.86 +/- 0.16 mmol/L), representing a 16.0% difference between diets. High-density lipoprotein (HDL) cholesterol and circulating triacylglycerol concentrations remained unaffected by treatment. Ratios of HDL:LDL and HDL:total cholesterol were higher (P <.01) by 22.0% and 11.0%, respectively, on FctO versus BT. Plasma total homocysteine remained unchanged with FctO, but decreased (P <.05) with control, hence higher (P <.05) end points were observed with FctO (6.95 +/- 0.33 micromol/L) versus BT (6.27 +/- 0.28 micromol/L). Plasma glutathione increased (P <.05) by 0.44 micromol/L with FctO supplementation. In conclusion, despite equivocal effects on homocysteine levels, consumption of a functional oil composed of MCT, phytosterols, and n-3 fatty acids for 27 days improves the overall cardiovascular risk profile of overweight women.

Topics: Adult; Cardiovascular Diseases; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cross-Over Studies; Dietary Supplements; Drug Combinations; Energy Metabolism; Fatty Acids, Omega-3; Female; Homocysteine; Humans; Middle Aged; Obesity; Oils; Phytosterols; Single-Blind Method; Triglycerides

Topics: Aged; Arteriosclerosis; Autopsy; Body Weight; Cholecystectomy; Cholelithiasis; Cholesterol; Cholesterol, Dietary; Diet; Diet Therapy; Dietary Fats; Fats, Unsaturated; Fatty Acids, Unsaturated; Humans; Male; Middle Aged; Obesity; Phytosterols; Time Factors

Obstructive sleep apnea (OSA) is closely linked to obesity and related adverse metabolic changes, including dyslipidemia. However, it is not clear whether OSA is an independent contributing factor to dyslipidemia, or the observed association is a reflection of a concomitant presence of obesity. Additionally, dyslipidemia is usually evaluated through measurement of parameters of routine lipid status, while more precise evaluation of lipid homeostasis is rarely performed in OSA. In this study, we analyzed markers of cholesterol synthesis and absorption in patients with OSA with respect to the presence of obesity and the disease severity.. Our results suggest that the presence of obesity and severe forms of OSA is characterized by elevated endogenous cholesterol synthesis. AHI was singled out as an independent determinant of the serum level of cholesterol synthesis marker lathosterol.

Topics: Chromatography, Liquid; Humans; Hypercholesterolemia; Obesity; Phytosterols; Severity of Illness Index; Sleep Apnea, Obstructive; Tandem Mass Spectrometry

Plant sterols (PSs) cannot be synthesized in mammals and are exclusively diet-derived. PSs cross the blood-brain barrier and may have anti-neuroinflammatory effects. Obesity is linked to lower intestinal uptake and blood levels of PSs, but its effects in terms of neuroinflammation-if any-remain unknown. We investigated the effect of high-fat diet-induced obesity on PSs in the brain and the effects of the PSs campesterol and β-sitosterol on in vitro microglia activation. Sterols (cholesterol, precursors, PSs) and polyunsaturated fatty acid-derived lipid mediators were measured in the food, blood, liver and brain of C57BL/6J mice. Under a PSs-poor high-fat diet, PSs levels decreased in the blood, liver and brain (>50%). This effect was reversible after 2 weeks upon changing back to a chow diet. Inflammatory thromboxane B2 and prostaglandin D2 were inversely correlated to campesterol and β-sitosterol levels in all brain regions. PSs content was determined post mortem in human cortex samples as well. In vitro, PSs accumulate in lipid rafts isolated from SIM-A9 microglia cell membranes. In summary, PSs levels in the blood, liver and brain were associated directly with PSs food content and inversely with BMI. PSs dampen pro-inflammatory lipid mediators in the brain. The identification of PSs in the human cortex in comparable concentration ranges implies the relevance of our findings for humans.

Topics: Animal Feed; Animals; Cells, Cultured; Cholesterol; Chromatography, Liquid; Diet, High-Fat; Disease Models, Animal; Fatty Acids, Unsaturated; Humans; Lipidomics; Liver; Male; Mice; Mice, Inbred C57BL; Microglia; Neuroinflammatory Diseases; Obesity; Phytosterols; Sitosterols; Tandem Mass Spectrometry

The aim of this study is to investigate the mechanism of anti-obesity effects of Aloe vera gel extract (AVGE) containing Aloe sterols. Previously, we reported that oral intake of Aloe vera components has an anti-diabetic and anti-obesity effect. This study was designed to assess the role of brown adipose tissue (BAT) in the anti-obesity effect of AVGE. Six-week-old male mice were divided into three groups; STD (standard diet), HFD (60% high fat diet) and AVGE (60% high fat diet with AVGE treatment). During 11 wk of AVGE administration, body weight has been monitored. Tissue samples were obtained to be measured the weight and evaluated the gene expressions. Mice treated with AVGE had suppressed body weight, and liver and fat weight gain. To investigate BAT activation, we measured the expression of mRNA related to BAT thermogenesis. Mice in the AVGE group had higher expression of Ucp1, Adrb3, and Cidea in BAT compared to HFD. Next, to investigate the possibility that AVGE induced hepatic FGF21, which is an important factor for nutrient and energy homeostasis including BAT regulation, in vitro study was conducted. HepG2 cell stimulated by AVGE were highly expressed FGF21. These results suggested that BAT activation partially contributes to mechanism of anti-obesity effect of Aloe sterols in diet-induced obesity (DIO) models. However, further study is needed to determine the predominant mechanism.

Topics: Adipose Tissue, Brown; Administration, Oral; Aloe; Animals; Anti-Obesity Agents; Diet, High-Fat; Dietary Fats; Energy Metabolism; Fibroblast Growth Factors; Hep G2 Cells; Humans; Liver; Male; Mice, Inbred C57BL; Obesity; Phytosterols; Phytotherapy; Plant Extracts; Plant Preparations; Thermogenesis; Weight Gain

Changes in cholesterol absorption and cholesterol synthesis may promote dyslipidemia and cardiovascular disease in individuals with type 2 diabetes mellitus (T2DM).. To assess cholesterol synthesis and absorption in lean individuals, obese individuals, and individuals with T2DM.. We measured lathosterol and lanosterol (markers of cholesterol synthesis) as well as campesterol and β-sitosterol (markers of cholesterol absorption) in the serum of 15 to 26 years old individuals with T2DM (n = 95), as well as their lean (n = 98) and obese (n = 92) controls.. Individuals with T2DM showed a 51% increase in lathosterol and a 65% increase in lanosterol compared to lean controls. Similarly, obese individuals showed a 31% increase in lathosterol compared to lean controls. Lathosterol and lanosterol were positively correlated with body mass index, fasting insulin and glucose, serum triglycerides, and C-reactive protein, and negatively correlated with HDL-cholesterol. In contrast, campesterol and β-sitosterol were not altered in individuals with T2DM. Moreover, campesterol and β-sitosterol were negatively correlated with body mass index, fasting insulin, and C-reactive protein and were positively correlated with HDL-cholesterol.. Adolescents and young adults with T2DM show evidence of increased cholesterol synthesis compared to non-diabetic lean controls. These findings suggest that T2DM may promote cardiovascular disease by increasing cholesterol synthesis, and provide additional rationale for the use of cholesterol synthesis inhibitors in this group.

Topics: Adolescent; Adult; Biomarkers; Body Mass Index; Case-Control Studies; Cholesterol; Diabetes Mellitus, Type 2; Humans; Obesity; Phytosterols; Sitosterols; Young Adult

(1) Background: Modern dietary patterns with a high intake of fat and fructose, as well as refined carbohydrates, closely relate to lipid/glucose metabolic disorders. The main objective of this study is to provide new thoughts in designing functional food with some lipid/glucose metabolism regulating effects for obese people. (2) Methods: The alleviating abilities of γ-oryzanol, phytosterol or ferulic acid-enriched wheat flour on lipid/glucose metabolic dysfunction were evaluated in male SD rats induced by a high-fat-fructose diet. The underlying mechanisms were clarified using western blot. (3) Results: In an in vitro cell model, γ-oryzanol, phytosterol and ferulic acid regulate lipid/glucose metabolism by increasing the phosphorylation of AMPK and Akt, and PI3K expression, as well as decreasing expressions of DGAT1 and SCD. The in vivo study shows that ferulic acid and γ-oryzanol-enriched flours are beneficial for managing body weight, improving glucose metabolism, hyperlipidemia and hepatic lipid accumulation. Phytosterol-enriched flour exerted remarkable effects in regulating hyperinsulinemia, insulin resistance and hyperuricemia. Western blot analysis of proteins from liver samples reveals that these enriched flours alleviated hepatic lipid accumulation and insulin resistance through their elevation in the phosphorylation of AMPK and Akt. (4) Conclusions: Our study indicates that these enriched flours can serve as a health-promoting functional food to regulate obesity-related lipid/glucose metabolic dysfunction in rats.

Topics: Animal Feed; Animals; Biomarkers; Blood Glucose; Coumaric Acids; Dietary Sugars; Disease Models, Animal; Flour; Food, Fortified; Fructose; Hep G2 Cells; Humans; Lipids; Male; Metabolic Diseases; Obesity; Phenylpropionates; Phytosterols; Rats, Sprague-Dawley; Signal Transduction; Triticum

It has been established in RCTs that high dose of phytosterols can significantly reduce blood cholesterol. However, it was uncertain whether low dose of phytosterols from daily diets was effective. In this study, we evaluated the associations between dietary phytosterols and body mass index (BMI), waist circumference (WC), blood glucose, serum lipid profiles and prevalence of overweight/obesity and abdominal obesity in healthy subjects.. Four hundred nine men and 503 women aged 18-60 years were included in this study. Dietary intakes of phytosterols were estimated using a validated food frequency questionnaire. Height, body weight, WC and blood pressure were measured, an oral glucose tolerance test was performed. Moreover, fasting serum triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDLc) and low density lipoprotein cholesterol (LDLc) were further determined.. When comparing extreme quartiles of dietary phytosterols, significant differences of BMI, WC, systolic blood pressure (SBP), diastolic blood pressure (DBP), serum TC and LDLc were found. Dietary phytosterols presented a negative association with BMI, WC, SBP, DBP, serum TC and LDLc (with and without adjustment for energy). After adjustment for confounders, we found higher dietary phytosterols were linked with lower prevalence of overweight/obesity (OR highest vs. lowest quartile = 0.487; 95% CI 0.234, 0.918 for men; OR highest vs. lowest quartile = 0.277; 95% CI 0.124, 0.619 for women) and abdominal obesity (OR highest vs. lowest quartile = 0.344; 95% CI 0.144, 0.819 for men; OR highest vs. lowest quartile = 0.321; 95% CI 0.140, 0.571 for women).. Higher dietary phytosterols were associated with lower BMI, WC, blood pressure, serum TC and LDLc and lower prevalence of overweight/obesity and abdominal obesity in Chinese adults.

Topics: Adolescent; Adult; Blood Glucose; Blood Pressure; Body Mass Index; China; Cholesterol, LDL; Cross-Sectional Studies; Female; Humans; Lipids; Male; Middle Aged; Obesity; Overweight; Phytosterols; Surveys and Questionnaires; Triglycerides; Waist Circumference; Young Adult

Impaired glucose metabolism during pregnancy may associate with changes in fetal cholesterol metabolism. We investigated if gestational diabetes mellitus (GDM) affects newborn cholesterol metabolism as determined by cord blood squalene and non-cholesterol sterols. Furthermore, we examined potential correlations between cord blood and maternal serum non-cholesterol sterols.. Pregnant women at risk for GDM (BMI>30 kg/m. The ratios of squalene and non-cholesterol sterols to cholesterol (100 × μmol/mmol of cholesterol) in cord blood did not differ between the infants born to mothers with GDM (n = 15) or mothers with normal glucose tolerance (n = 13). The ratios of sitosterol and campesterol to cholesterol in the cord blood correlated with the corresponding maternal serum ratios (r = 0.70, p < 0.0001) in both groups.. In obese women under good glycaemic control, GDM did not affect newborn cholesterol metabolism. Cord blood sitosterol and campesterol ratios to cholesterol correlated with the corresponding maternal serum ratios thus potentially reflecting maternal-fetal cholesterol transport.

Topics: Adult; Biomarkers; Blood Glucose; Case-Control Studies; Cholestanol; Cholesterol; Diabetes, Gestational; Female; Fetal Blood; Finland; Humans; Infant, Newborn; Maternal-Fetal Exchange; Obesity; Phytosterols; Pregnancy; Sitosterols; Squalene

Pistachios contain beneficial substances such as unsaturated fatty acids, phytosterols, and polyphenols. In the present study, we investigated if pistachio consumption is able to prevent or to revert hyperglycemia, dyslipidemia, hepatic steatosis, and adipose tissue morphological alterations caused by high fat diet (HFD) in the mouse. Moreover, the impact of pistachio intake on the mRNA expression of peroxisome proliferator-activated receptor γ (

Topics: Adipose Tissue; Animals; Cholesterol; Diet; Diet, High-Fat; Dyslipidemias; Fatty Acid Synthases; Fatty Liver; Hypertriglyceridemia; Lipid Metabolism; Liver; Male; Mice, Inbred C57BL; Mice, Obese; Nuts; Obesity; Phytosterols; Pistacia; Plant Extracts; Polyphenols; PPAR gamma; RNA, Messenger; Stearoyl-CoA Desaturase; Sterol Regulatory Element Binding Protein 1

To investigate the cholesterol-lowering effectiveness of a phytosterol/α-lipoic acid (PS/αLA) therapy, thirty-two male Zucker rats were randomly assigned to 1 of 4 diets for 30 days: (i) high fat diet (HF, 40% energy from fat); (ii) HF diet supplemented with 3% phytosterols; (iii) HF diet supplemented with 0.25% αLA; or (iv) HF diet supplemented with PS (3%) and αLA (0.25%, PS/αLA). Compared with the HF diet, combination PS/αLA proved more effective in reducing non-HDL cholesterol (-55%) than either the PS (-24%) or the αLA (-25%) therapies alone. PS supplementation did not affect LDL particle number, however, αLA supplementation reduced LDL particle number when supplemented alone (-47%) or in combination with PS (-54%). Compared with the HF-fed animals, evidence of increased HDL-particle number was evident in all treatment groups to a similar extent (21-22%). PS-mediated interruption of intestinal cholesterol absorption was evident by increased fecal cholesterol loss (+52%) and compensatory increase in HMG-CoA reductase mRNA (1.6 fold of HF), however, αLA supplementation did not affect fecal cholesterol loss. Hepatic mRNA and protein expression patterns suggested that αLA modulated multiple aspects of cholesterol homeostasis including reduced synthesis (HMG-CoA reductase mRNA, 0.7 fold of HF), reduced bile acid synthesis (CYP7a1 expression, 0.17 of HF), and increased cholesterol clearance (reduced PCSK9 mRNA, 0.5 fold of HF; increased LDLr protein, 2 fold of HF). Taken together, this data suggests that PS and αLA work through unique and complementary mechanisms to provide a superior and more comprehensive cholesterol lowering response than either therapy alone.

Topics: Acyl Coenzyme A; Animals; Anticholesteremic Agents; Antioxidants; Bile Acids and Salts; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diet, High-Fat; Dietary Fats; Dietary Supplements; Drug Synergism; Hypercholesterolemia; Intestinal Absorption; Liver; Male; Obesity; Phytosterols; Proprotein Convertase 9; Rats, Zucker; RNA, Messenger; Serine Endopeptidases; Thioctic Acid

Obesity is a multifactorial disorder which is closely associated with hyperlipidemia. Avocados are edible fruits traditionally consumed for various health benefits including body weight reduction.. To determine the hypolipidemic and anti-obesity effect of hydro-alcoholic fruit extract of avocado (HFEA) in rats fed with high fat diet (HFD).. Male Sprague Dawley rats were divided into four groups. Groups 1 and 2 rats were fed with normal diet. Groups 3 and 4 rats were fed with HFD for 14 weeks. In addition, Groups 2 and 4 rats were co-administered with 100 mg/kg body weight of HFEA from 3rd week onwards.. The HFEA was subjected to HPLC to quantify the major phytonutrients. Body mass index (BMI), adiposity index (ADI), total fat pad mass (TFP), blood lipid levels were determined in all the groups of rats. The mRNA expression of fatty acid synthase (FASN), lipoprotein lipase (LPL), fibroblast growth factor 21 (FGF21) and leptin was also assessed.. HFEA was found to contain flavonoids: rutin-141.79, quercetin-5.25, luteolin-165, phenolic compounds: gallic acid-198.57, ellagic acid-238.22, vanillic acid-4.79 and phytosterols: betasitosterol-70, stigmasterol-12.5 (mg/100 g). HFEA reduced BMI, ADI, TFP, blood cholesterol, triglycerides, and LDL in rats fed with HFD. Serum leptin was found reduced in HFEA co-administered rats. The mRNA expression of FASN, LPL, and leptin in subcutaneous and visceral adipose tissue was found to be significantly reduced in HFEA co-administered rats. The gene expression of fibroblast growth factor-21 (FGF21) was found to be significantly increased in HFEA treated rats when compared to HFD control rats.. The hypolipidemic effect of HFEA may be partly due to its modulating effect on endogenous fat synthesis and adiponectin formation through the transcription factor FGF21. The results also show that avocado fruit extract has profound influence on leptin activity, which controls satiety and hunger to regulate the food intake.

Topics: Animals; Body Mass Index; Chemical Fractionation; Cholesterol; Diet, High-Fat; Fatty Acid Synthase, Type I; Fibroblast Growth Factors; Flavonoids; Fruit; Hyperlipidemias; Hypolipidemic Agents; Leptin; Lipoprotein Lipase; Male; Obesity; Persea; Phenols; Phytosterols; Plant Extracts; Rats; Rats, Sprague-Dawley; Triglycerides

Obesity is now a worldwide health problem. Glucose-dependent insulinotropic polypeptide (GIP) is a gut hormone that is secreted following the ingestion of food and modulates energy metabolism. Previous studies reported that lowering diet-induced GIP secretion improved energy homeostasis in animals and humans, and attenuated diet-induced obesity in mice. Therefore, food-derived GIP regulators may be used in the development of foods that prevent obesity. Rice bran oil and its components are known to have beneficial effects on health. Therefore, the aim of the present study was to clarify the effects of the oil-soluble components of rice bran on postprandial GIP secretion and obesity in mice. Triterpene alcohols [cycloartenol (CA) and 24-methylene cycloartanol (24Me)], β-sitosterol, and campesterol decreased the diet-induced secretion of GIP in C57BL/6J mice. Mice fed a high-fat diet supplemented with a triterpene alcohol and sterol preparation (TASP) from rice bran for 23 wk gained less weight than control mice. Indirect calorimetry revealed that fat utilization was higher in TASP-fed mice than in control mice. Fatty acid oxidation-related gene expression in the muscles of mice fed a TASP-supplemented diet was enhanced, whereas fatty acid synthesis-related gene expression in the liver was suppressed. The treatment of HepG2 cells with CA and 24Me decreased the gene expression of sterol regulatory element-binding protein (SREBP)-1c. In conclusion, we clarified for the first time that triterpene alcohols and sterols from rice bran prevented diet-induced obesity by increasing fatty acid oxidation in muscles and decreasing fatty acid synthesis in the liver through GIP-dependent and GIP-independent mechanisms.

Topics: Alcohols; Animals; Diet, High-Fat; Energy Metabolism; Fatty Acids; Gastric Inhibitory Polypeptide; Hep G2 Cells; Humans; Intra-Abdominal Fat; Liver; Male; Mice, Inbred C57BL; Obesity; Oryza; Phytosterols; Phytotherapy; Postprandial Period; Triterpenes; Weight Gain

Rice bran enzymatic extract (RBEE) has advantages compared to the original rice bran or its oils including water solubility, lack of rancidity and increased content in high nutritional proteins and nutraceutical compounds, particularly phytosterols, γ-oryzanol and tocols. Our aim was to determine the beneficial effects of RBEE in the pathogenesis of metabolic syndrome in obese Zucker rats.. Obese Zucker rats and their lean littermates were fed a 1 and 5 % RBEE-supplemented diet (O1, O5, L1 and L5). Simultaneously, obese and lean Zucker rats, fed a standard diet, were used as controls (OC and LC, respectively). Body weight, food and water intake, and systolic blood pressure were weekly evaluated. After treatment, biochemical assays of serum glucose, insulin, triglycerides (TG), total cholesterol (TC), non-esterified fatty acids (NEFA), adiponectin and nitrates (NO((x))) were determined.. RBEE treatment reduced circulating levels of TG and TC, whereas increased HDL-cholesterol without altering NEFA values in obese rats. The extract also induced a significant dose-dependent reduction of hypertension linked to obesity. RBEE of 5 % improved insulin resistance and subsequently reduced HOMA-IR index without altering serum glucose levels. Obese animals treated with RBEE showed partial restoration of adiponectin levels and a significant attenuation of pro-inflammatory values of NO((x)).. These findings evidence the nutraceutical properties of RBEE against the pathogenesis of metabolic syndrome by attenuating dyslipidemia, hypertension and insulin resistance as well as by restoring hypoadiponectinemia associated to obesity.

Topics: Adiponectin; Animals; Blood Glucose; Blood Pressure; Body Weight; Cholesterol; Diet; Dyslipidemias; Fatty Acids, Nonesterified; Hypertension; Insulin; Insulin Resistance; Metabolic Syndrome; Nitrates; Obesity; Oryza; Phenylpropionates; Phytosterols; Plant Extracts; Rats; Rats, Zucker; Triglycerides; Water

Obesity is associated with increased systemic and airway oxidative stress, which may result from a combination of adipokine imbalance and antioxidant defenses reduction. Obesity-mediated oxidative stress plays an important role in the pathogenesis of dyslipidemia, vascular disease, and nonalcoholic hepatic steatosis. The antidyslipidemic activity of pigeon pea were evaluated by high-fat diet (HFD) hamsters model, in which the level of high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), total cholesterol (TC), and total triglyceride (TG) were examined. We found that pigeon pea administration promoted cholesterol converting to bile acid in HFD-induced hamsters, thereby exerting hypolipidemic activity. In the statistical results, pigeon pea significantly increased hepatic carnitine palmitoyltransferase-1 (CPT-1), LDL receptor, and cholesterol 7α-hydroxylase (also known as cytochrome P450 7A1, CYP7A1) expression to attenuate dyslipidemia in HFD-fed hamsters; and markedly elevated antioxidant enzymes in the liver of HFD-induced hamsters, further alleviating lipid peroxidation. These effects may attribute to pigeon pea contained large of unsaturated fatty acids (UFA; C18:2) and phytosterol (β-sitosterol, campesterol, and stigmasterol). Moreover, the effects of pigeon pea on dyslipidemia were greater than β-sitosterol administration (4%), suggesting that phytosterone in pigeon pea could prevent metabolic syndrome.

Topics: Animals; Antioxidants; Cajanus; Carnitine O-Palmitoyltransferase; Cholesterol; Cholesterol 7-alpha-Hydroxylase; Cholesterol, HDL; Cholesterol, LDL; Chromatography, High Pressure Liquid; Cricetinae; Diet, High-Fat; Disease Models, Animal; Hypercholesterolemia; Lipid Peroxidation; Liver; Male; Obesity; Oxidative Stress; Phytosterols; Receptors, LDL; Sitosterols; Stigmasterol; Triglycerides

Topics: Adipose Tissue; Atherosclerosis; Blood Pressure; Capsaicin; Cardiovascular Diseases; Databases, Factual; Diabetes Mellitus, Type 2; Dietary Fats; Dietary Proteins; Endotoxemia; Feeding Behavior; Flavonoids; Fructose; Glycation End Products, Advanced; Humans; Hypertension; Hyperuricemia; Lipid Metabolism; Neuroimaging; Obesity; Phytosterols; Stroke; Thermogenesis

We investigated the effects of the oral administration of lophenol (Lo) and cycloartanol (Cy), two kinds of antidiabetic phytosterol isolated from Aloe vera , on glucose and lipid metabolism in Zucker diabetic fatty (ZDF) rats. We demonstrated that the administrations of Lo and Cy suppressed random and fasting glucose levels and reduced visceral fat weights significantly. It was also observed that treatments with Lo and Cy decreased serum and hepatic lipid concentrations (triglyceride, nonesterified fatty acid, and total cholesterol). Additionally, Lo and Cy treatments resulted in a tendency for reduction in serum monocyte chemotactic protein-1 (MCP-1) level and an elevation in serum adiponectin level. Furthermore, the expression levels of hepatic genes encoding gluconeogenic enzymes (G6 Pase, PEPCK), lipogenic enzymes (ACC, FAS), and SREBP-1 were decreased significantly by the administrations of aloe sterols. In contrast, Lo and Cy administration increased mRNA levels of glycolysis enzyme (GK) in the liver. It was also observed that the hepatic β-oxidation enzymes (ACO, CPT1) and PPARα expressions tended to increase in the livers of the Lo- and Cy-treated rats compared with those in ZDF-control rats. We therefore conclude that orally ingested aloe sterols altered the expressions of genes related to glucose and lipid metabolism, and ameliorated obesity-associated metabolic disorders in ZDF rats. These findings suggest that aloe sterols could be beneficial in preventing and improving metabolic disorders with obesity and diabetes in rats.

Topics: Acetyl-CoA Carboxylase; Acyl-CoA Oxidase; Administration, Oral; Aloe; Animals; Gene Expression; Gene Expression Profiling; Humans; Liver; Male; Metabolic Diseases; Obesity; Phosphoenolpyruvate Carboxykinase (GTP); Phytosterols; Plant Extracts; Rats; Rats, Zucker

Previous research indicates that animals fed a high fat (HF) diet supplemented with disodium ascorbyl phytostanyl phosphate (DAPP) exhibit reduced mass accumulation when compared to HF control. This compound is a water-soluble phytostanol ester and consists of a hydrophobic plant stanol covalently bonded to ascorbic acid (Vitamin C). To provide insight into the mechanism of this response, we examined the in vivo effects of a high fat diet supplemented with ascorbic acid (AA) in the presence and absence of unesterified phytosterols (PS), and set out to establish whether the supplements have a synergistic effect in a diet-induced obesity mouse model. Our data indicate that HF diet supplementation with a combination of 1% w/w phytosterol and 1% w/w ascorbic acid results in reduced mass accumulation, with mean differences in absolute mass between PSAA and HF control of 10.05%; and differences in mass accumulation of 21.6% (i.e. the PSAA group gained on average 21% less mass each week from weeks 7-12 than the HF control group). In our previous study, the absolute mass difference between the 2% DAPP and HF control was 41%, while the mean difference in mass accumulation between the two groups for weeks 7-12 was 67.9%. Mass loss was not observed in animals supplemented with PS or AA alone. These data suggest that the supplements are synergistic with respect to mass accumulation, and the esterification of the compounds further potentiates the response. Our data also indicate that chronic administration of PS, both in the presence and absence of AA, results in changes to fecal output and food transit time, providing insight into the possibility of long-term changes in intestinal function related to PS supplementation.

Topics: Adiposity; Animals; Ascorbic Acid; Calorimetry; Dietary Fats; Dietary Supplements; Drug Evaluation, Preclinical; Eating; Feces; Gastrointestinal Transit; Male; Mice; Mice, Inbred C57BL; Obesity; Oxygen Consumption; Phytosterols; Weight Gain

The differences in cholesterol metabolism after the 2 most common forms of obesity surgery, Roux-en-Y gastric bypass (RYGB) and gastric banding (GB), have not been well characterized. In this study, effects of RYGB and GB on cholesterol absorption and synthesis were investigated. To this aim, 1-year follow-up of cholesterol metabolism in 2 nonrandomized cohorts undergoing either RYGB (n = 29; age, 45.2 +/- 7.7 years; body mass index [BMI], 46.0 +/- 6.1 kg/m(2)) or GB (n = 26; age, 45.9 +/- 8.6 years; BMI, 50.1 +/- 7.7 kg/m(2)) was performed in a university hospital center specializing in the treatment of morbid obesity. Serum markers of cholesterol synthesis (cholestenol, desmosterol, and lathosterol) and cholesterol absorption (campesterol, sitosterol, avenasterol, and cholestanol) were measured preoperatively and at follow-up and expressed as ratios to cholesterol. As expected based on observed weight loss (25% after RYGB and 17% after GB, P < .001 between groups), both operations decreased serum levels of cholesterol synthesis markers by 12% to 28% (all Ps < .001). A decrease in cholesterol absorption markers was only observed after RYGB (-26% for sitosterol) and not after GB (+16%, P = 2 x 10(-6) for difference between the groups). The difference in sitosterol ratio between the groups remained significant after adjustment for age, BMI, fasting insulin levels, and nutritional status (P = 2 x 10(-4)), indicating a specific effect related to RYGB. We conclude that decrease in cholesterol absorption is a novel beneficial effect of RYGB. Together with an improved control of blood glucose, this may contribute to a better cardiovascular risk profile after RYGB.

Topics: Adult; Anastomosis, Roux-en-Y; Bariatric Surgery; Blood Glucose; Body Height; Body Mass Index; Body Weight; Cholesterol; Cholesterol, Dietary; Cholesterol, LDL; Female; Gastric Bypass; Humans; Intestinal Absorption; Liver; Male; Middle Aged; Obesity; Phytosterols; Sterols

Cholesterol synthesis is upregulated and absorption downregulated in insulin resistance and in type 2 diabetes. We investigated whether alterations in cholesterol metabolism are observed across the glucose tolerance status, from normoglycemia through impaired glucose tolerance to type 2 diabetes, in 781 randomly selected men 45 to 70 years of age from a population-based Metabolic Syndrome in Men Study. Cholesterol metabolism was assayed using surrogate serum markers, squalene, and noncholesterol sterols. The study population was classified into subgroups according to glucose tolerance as follows: normoglycemia, impaired fasting glucose, impaired glucose tolerance, and type 2 diabetes. LDL cholesterol did not differ between the groups. Cholesterol synthesis markers were lowest and absorption markers highest in normoglycemia. Sitosterol was lower in subjects with impaired fasting glucose compared with normoglycemic subjects (113 +/- 7 vs. 136 +/- 3 10(2) mumol/mmol of cholesterol, P < 0.05). LDL cholesterol was not associated with lathosterol/sitosterol ratio, a marker of cholesterol metabolism. Peripheral insulin sensitivity evaluated by the Matsuda index was associated with the lathosterol/sitosterol ratio in the entire population (r = -0.457, P < 0.001) and with that of lathosterol/cholestanol independently of obesity. In conclusion, cholesterol metabolism was altered already from subjects with impaired fasting glucose. Upregulated cholesterol synthesis was associated with peripheral insulin resistance independent of obesity.

Topics: Absorption; Aged; Biomarkers; Cholestanol; Cholesterol; Diabetes Mellitus, Type 2; Glucose; Humans; Insulin; Linear Models; Male; Metabolic Syndrome; Middle Aged; Obesity; Phytosterols; Squalene

We investigated the associations between indices of cholesterol metabolism and features of the metabolic syndrome (MS) in the presence and absence of type-2 diabetes (T2DM).. Men with the MS (N=140) and 10 age- and sex-matched controls were recruited. Plasma lathosterol and campesterol were measured by gas chromatography-mass spectrometry, and their ratios to total cholesterol were used to estimate cholesterol metabolism.. Compared with healthy controls, MS subjects had significantly higher lathosterol:cholesterol and lower campesterol:cholesterol ratios (p<0.05). In the MS subjects without T2DM (N=82), campesterol:cholesterol ratio was positively associated with age and negatively associated with plasma triglyceride and insulin concentrations, while in MS subjects with T2DM (N=58), the ratio was positively associated with age and adiponectin concentration, and negatively associated with BMI and insulin. Age and fasting insulin were independent predictors of campesterol:cholesterol ratio in MS subjects with T2DM. There was a significant negative association between plasma lathosterol:cholesterol with campesterol:cholesterol ratio (r=-0.436, p=0.014) in MS subjects without T2DM but not in MS subjects with T2DM.. Cholesterol absorption efficiency was lower and cholesterol synthesis higher in MS subjects with or without T2DM compared with healthy individuals. Moreover, the reciprocal relationship between cholesterol synthesis and cholesterol absorption is lost in the presence of diabetes.

Topics: Adiponectin; Apolipoprotein A-I; Apolipoproteins; Biomarkers; Blood Glucose; Blood Pressure; Cholesterol; Diabetes Mellitus, Type 2; Female; Gas Chromatography-Mass Spectrometry; Homeostasis; Humans; Male; Metabolic Syndrome; Middle Aged; Obesity; Phytosterols; Reference Values; Triglycerides

Most studies have focused on the cholesterol-lowering activity of phytosterols; however, other biological actions have also been attributed to these plant compounds. In this study, we investigated whether phytosterols could delay (progression phase) and/or reverse (regression phase) insulin resistance or type 2 diabetes mellitus in an experimental mouse model of diet-induced obesity, insulin resistance, and diabetes. Body mass, plasma lipid levels, insulin resistance, and hyperglycemia were determined. Phytosterol intake did not improve these metabolic parameters. Therefore, we were unable to substantiate any protective effect of phytosterol intake on diabetes development or regression in the mouse model used.

Topics: Animals; Cholesterol; Diabetes Mellitus, Type 2; Dietary Fats; Disease Susceptibility; Insulin Resistance; Male; Mice; Mice, Inbred C57BL; Obesity; Phytosterols

Disodium ascorbyl phytostanol phosphate (FM-VP4) is a cholesterol absorption inhibitor, a new class in cholesterol-lowering drug. Previous research on the lipid-lowering and anti-atherosclerotic effects of this drug has reported that administration of FM-VP4 results in a decrease in body mass. This study examined the FM-VP4 dose-dependent mass loss in mice and investigated some potential mechanisms by which decreased mass accumulation may have occurred. The effect of FM-VP4 administration on pre-obese mice was also tested.. We conducted a dose-dependent study on mouse growth, food and water intake, organ mass, femur length, resting metabolic rate (RMR), maximal oxygen consumption under various conditions (VO(2swim) and VO(2heliox)), and fecal fat and plasma assessment for cholesterol and non-esterified fatty acids (NEFA) in mice fed a low fat (LF) or high fat (HF) diet, with or without FM-VP4. The ratio of lean to fat body mass of each animal was also assessed using magnetic resonance spectroscopy. To establish the effect of FM-VP4 on pre-existing obesity, mice were fed a high fat diet for 57 days, followed by administration of a diet containing 2% (w/w) FM-VP4 for 93 days.. Animals exhibit a dose-dependent decline in body mass without a concomitant decrease in food intake, water intake, spleen, heart, or kidney mass, femur length or lean body mass. A dose-dependent trend toward a reduction in fat mass was observed in both high fat and low fat diet groups, becoming significant at a 1 and 2% FM-VP4 dosage (w/w). No FM-VP4 induced change in food or water intake, or resting metabolic rate was observed; however, an increase in VO(2swim) was observed in the 2% FM-VP4 group over HF control. These findings were also observed in the pre-obese group treated with 2% FM-VP4.. We found a dose dependent reduction in mass accumulation in mice treated with FM-VP4. This loss of mass is not due to an increase in resting metabolic rate or decreased food or water intake. The only tissues exhibiting a decrease in mass with FM-VP4 treatment are liver and body fat. Fecal fat content increased significantly with FM-VP4 treatment in a dose-dependent manner, suggesting that the treatment reduces mass accumulation through decreased absorption or increased excretion of lipids.

Topics: Adipose Tissue; Animals; Anticholesteremic Agents; Body Composition; Body Weight; Dose-Response Relationship, Drug; Feces; Lipids; Male; Mice; Mice, Inbred C57BL; Obesity; Oxygen Consumption; Phytosterols

The objective of this study was to determine the effects of disodium ascorbyl phytostanyl phosphate (DAPP), a novel hydrophilic phytostanol analogue, on energy homeostasis, including body weight and intestinal energy absorption, and plasma triglyceride concentrations, in hamsters.. Male Golden Syrian hamsters (n = 50) were fed for 5 weeks with experimental diets varying in cholesterol and phytostanol content. Diets included (i) non-cholesterol (semipurified diet without added cholesterol), (ii) cholesterol-control (semipurified diet with 0.25% cholesterol), (iii) stanol (cholesterol-control with 1% free phytostanols), (iv) DAPP 0.7% (cholesterol-control with 0.71% DAPP) or (v) DAPP 1.4% (cholesterol-control with 1.43% DAPP). Fecal samples were collected continuously for 3 days on week 3, and fecal energy output was measured by bomb calorimetry.. Hamsters fed 1.4% DAPP gained less (P<0.05) weight than hamsters fed non-cholesterol and stanol diets. Diets had no effect on total food consumption or gross energy intake after 5 weeks, but lower (P<0.05) weekly food consumptions in hamsters fed 1.4% DAPP were observed at weeks 1 and 2 of the experiment in comparison to animals fed the non-cholesterol diet. In comparison to non-cholesterol and cholesterol-control diets, DAPP 1.4% increased (P<0.01) fecal energy output by 47 and 46%, respectively. In hamsters supplemented with 1.4% DAPP, plasma triglyceride concentrations were 45% lower (P<0.05) than in cholesterol-control fed hamsters. Furthermore, plasma triglyceride levels in the DAPP 1.4% group was 49% lower (P<0.01) than in the stanol group, despite the fact that both diets contained equivalent amounts of phytostanols. The lower concentration of DAPP (0.7%) also reduced plasma triglycerides (P<0.05) compared with the stanol diet.. Stanol-ascorbate decreases body weight gain in hamsters, likely due to lower energy absorption at the intestinal level. In addition to its previously observed powerful cholesterol-lowering effect, DAPP has a hypotriglyceridemic function in hamsters.

Topics: Animals; Calorimetry; Cholesterol, Dietary; Cricetinae; Diet, Reducing; Eating; Energy Metabolism; Feces; Hypolipidemic Agents; Intestinal Mucosa; Male; Mesocricetus; Obesity; Phytosterols; Random Allocation; Sitosterols; Triglycerides

The purpose of this study was to determine if Disodium Ascorbyl Phytostanol Phosphates (FM-VP4) alters animal body weight and plasma lipid levels in a dietary-induced obese mouse model.. Twenty-four C57BL6 mice (28 days old) were housed individually and fed a standard mouse diet for 2 weeks upon arrival. After 2 weeks the animals were weighed and divided in 4 groups of similar average weight, and the groups received a low fat (10% kcal from fat) and high fat (45% kcal from fat) diet with or without FM-VP4 (2% w/w) for 12 continuous weeks. Food, water and caloric intake and body weight were recorded on a daily basis throughout the duration of the study. Following the 12th week of the study all animals were humanely sacrificed and blood and abdominal fat pads were harvested for further analysis. Plasma cholesterol, triglyceride, AST/ALT and creatinine levels were measured using enzymatic kits.. There is a significant difference in weight gain between the low-fat diet and the low-fat diet + 2% w/w FM-VP4 treatment groups (P<0.05), as well as between the high-fat diet and the high-fat diet + 2% w/w FM-VP4 treatment groups (P<0.05). However, the reduction of weight gain of the high-fat diet + 2% FM-VP4 treatment group compared to the high-fat group was 51%, while the reduction in weight gain between the low-fat diet + 2% w/w FM-VP4 treatment group and the low-fat diet group was 17% over the duration of the study. No significant differences in food and water intakes, serum creatinine and AST/ALT levels were observed between the four groups. No significant differences in caloric intake between the low-fat diet and the low-fat diet + 2% w/w FM-VP4. However, a significant difference in caloric intake between high-fat diet and the high-fat diet + 2% w/w FM-VP4 treatment groups was observed. In addition, significant reductions in plasma cholesterol levels and abdominal fat pad weight between diet alone and diet + FM-VP4 treatment groups were observed.. These findings suggest that FM-VP4 may have potential weight-loss and cholesterol lowering activity in both High Fat and Low Fat Diets treated groups.

Topics: Abdominal Fat; Animals; Anti-Obesity Agents; Body Weight; Cholesterol; Diet, Fat-Restricted; Dietary Fats; Disease Models, Animal; Male; Mice; Mice, Inbred C57BL; Obesity; Phytosterols

The purpose of this investigation was to determine the effects of Phytostanol Phosphoryl Ascorbate (FM-VP4) on insulin resistance, hyperglycemia, plasma lipid levels, body weight, and gastrointestinal absorption of exogenous cholesterol in Zucker (fa/fa) fatty and lean rats. A group of 12 age-matched male obese (n = 6) and lean (n = 6) Zucker rats were administered 250 mg/kg twice a day (as 2% FM-VP4 in drinking water) for 30 consecutive days. Fasted blood samples prior to and following treatment were taken from all rats for glucose, lipid, insulin, and leptin determination. An oral glucose tolerance test was also carried out at the end of the treatment protocol. In addition, male obese (n = 7) and lean (n = 8) Zucker rats were coadministered a single oral gavage of [(3)H]cholesterol plus cold cholesterol with or without FM-VP4 (20 mg/kg) dissolved in Intralipid and the plasma concentration of the radiolabel was determined 10 h following the dose. FM-VP4 30-day treatment did not alter body weight, morning glucose, insulin, lipids, and leptin concentrations. There was no alteration in glucose tolerance in the nondiabetic, normoglycemic lean group; however, there was a highly significant improvement in glucose tolerance in the fatty group following FM-VP4 treatment. In addition, the insulin response to oral glucose showed no significant change in nondiabetic lean rats, whereas there was a change in the insulin secretory profile in the fatty group following FM-VP4 treatment. Furthermore, following a single oral gavage of FM-VP4 resulted in a significant decrease in the percentage of radiolabeled cholesterol absorbed. These findings suggest that FM-VP4 treatment to fatty Zucker rats could result in increased glucose responsiveness of the insulin secreting pancreatic beta cells. Furthermore, our findings suggest that FM-VP4 may only be effective presystemically. Systemic administration of FM-VP4 is warranted to determine the therapeutic potential of this effect.

Topics: Animals; Blood Glucose; Body Weight; Cholesterol; Cholesterol, Dietary; Glucose Tolerance Test; Hyperglycemia; Hypoglycemic Agents; Insulin Resistance; Intestinal Absorption; Leptin; Lipids; Male; Obesity; Phytosterols; Rats; Rats, Zucker

Because dietary fat appears to be an effective vehicle for dispensing plant sterols into the diet, a special plant-sterol-containing ingredient has recently been developed. This ingredient is a plant sterol suspension in oil in which the sterols are in microcrystalline form. The objective of the present study was to analyse the cholesterol-lowering effects and safety of two different plant sterol preparations, an orally administered microcrystalline plant sterol suspension (MPS) in rapeseed oil and a powdered plant sterol supplement, in obese Zucker rats. Dietary plant sterol supplements (0.5%, w/w) were given concurrently with a high cholesterol diet (HCD, 1% cholesterol and 18% fat, w/w). No significant changes in serum triglyceride, blood glucose, serum glutamate oxaloacetic transaminase and glutamic pyruvic transaminase values or body and liver weights were observed. The powdered plant sterol supplement lowered the serum cholesterol by 25% (P < 0.05) and the MPS diet by 35% (P < 0.001) compared with HCD by the end of the 12-week experiment. Interestingly, the plant sterol supplements also produced a marked reduction in serum ubiquinone levels, suggesting a possible effect on isoprene synthesis. Unlike the powdered plant sterol, both MPS and plain rapeseed oil decreased the serum baseline diene conjugation values, suggesting that they protect against oxidative stress-induced lipid peroxidation in rats. This lipid peroxidation diminishing effect is probably due to some antioxidative components in rapeseed oil. These findings indicate that an unesterified plant sterol, such as the microcrystalline suspension in oil, effectively prevents cholesterol absorption in obese Zucker rats.

Topics: Administration, Oral; Animals; Chemistry, Pharmaceutical; Cholesterol, Dietary; Fatty Acids, Monounsaturated; Female; Hypercholesterolemia; Hypolipidemic Agents; Intestinal Absorption; Lipid Peroxidation; Obesity; Phytosterols; Plant Oils; Powders; Rapeseed Oil; Rats; Rats, Zucker; Sitosterols

Weight reduction in obese type 2 diabetes increases the absorption efficiency of cholesterol and serum plant sterol levels from baseline. However, there is no information on the effects of acute restriction of calories and lack of dietary cholesterol and plant sterols on serum cholesterol precursor and plant sterols and on cholesterol metabolism. Thus, 10 obese (BMI>30 kg/m(2)) type 2 diabetes subjects consumed very low energy diet virtually free of cholesterol, cholestanol and plant sterols for 3 months.. Serum sterols were measured with gas-liquid chromatography.. Body weight was reduced by 15.5+/-1.7 kg (p<0.001), serum cholesterol by 21+/-3%, triglycerides 45+/-5%, glucose 23+/-3%, insulin 59+/-5% and HbAIc by 8+/-2%, whereas serum sex hormone binding globulin increased by 108+/-25% (p<0.05-0.001 for all). Serum desmosterol and lathosterol to cholesterol ratios (indicators of cholesterol synthesis) were significantly decreased by 20% suggesting that cholesterol synthesis was suppressed. Serum squalene ratio was unchanged. Despite lack of dietary plant sterols and cholestanol, serum campesterol and sitosterol ratios (indicators of cholesterol absorption efficiency) only tended to decrease, whereas serum cholestanol ratio, also an absorption indicator, was increased by 33+/-3% (p<0.001), and its ratios to campesterol and sitosterol were increased by 60% and 31%, suggesting that sterol absorption efficiency might have been increased and their turnover reduced.. In obese type 2 diabetes, restriction of calories and dietary sterols improved markedly control of diabetes, decreased serum cholesterol precursor sterols suggesting that cholesterol synthesis was decreased, but only tended to decrease serum values of plant sterols probably due to their release from the adipose tissues associated with their impaired turnover.

Topics: Cholesterol; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet, Reducing; Female; Humans; Male; Middle Aged; Obesity; Phytosterols; Squalene; Sterols; Weight Loss

In most hypertensive rat models, serum total cholesterol is typically low and the cholesterol is primarily in the HDL rather than the LDL fraction. This difference from humans usually makes these animals unsuitable for experimental atherosclerosis studies. In the present study, we induced severe hypercholesterolemia including a 10-fold increase in serum LDL cholesterol, endothelial dysfunction and hypertension as well as vascular and renal damage in obese Zucker rats by feeding a human-type high fat, high cholesterol and high salt diet (butter 18, cholesterol 1 and NaCl 6 g/100 g dry weight). Supplementation of this atherogenic diet with plant sterols (1 g/100 g) and replacing the NaCl partially by calcium, magnesium and potassium effectively prevented the diet-induced increases in total and LDL cholesterols and 24-h systolic and mean blood pressures, and markedly improved endothelial function. Plant sterols and the minerals also protected against vascular and renal damage and extended the life span of the obese Zucker rats by 60% compared with the rats fed the atherogenic diet. Our findings suggest that human-type cardiovascular disorders can be induced in obese Zucker rats by feeding a human-type atherogenic diet. This seems to be a suitable animal model for experimental studies on atherosclerosis and hypertension as well as for evaluating new dietary approaches to reducing cardiovascular risk.

Topics: Animals; Arteriosclerosis; Blood Pressure; Calcium, Dietary; Cholesterol; Diet, Atherogenic; Dietary Supplements; Disease Models, Animal; Female; Hypertension; Magnesium; Minerals; Obesity; Phytosterols; Potassium, Dietary; Rats; Rats, Zucker; Risk Factors

Cholesterol metabolism was studied in 64 subjects with type 2 diabetes who had body weight ranging from normal to obese, to find out whether weight interferes with cholesterol metabolism in diabetes.. Cholesterol absorption was measured with peroral isotopes and by assaying serum plant sterol and cholestanol to cholesterol ratios, cholesterol synthesis with sterol balance, and measuring serum cholesterol precursor ratios.. The study population was divided into normal-weight (body mass index, 24.1 +/- 0.4 kg/m2; mean +/- SEM; n = 20) and obese (31.0 +/- 0.5 kg/m2; n = 44) groups. Despite similar serum cholesterol and blood glucose values, fecal neutral sterol excretion, cholesterol and bile acid synthesis, cholesterol turnover (1649 +/- 78 vs. 1077 +/- 52 mg/d; p < 0.001), and serum cholesterol precursors were higher, and cholesterol absorption % (32 +/- 1 vs. 40 +/- 2%; p < 0.05), serum cholestanol, and plant sterols were lower in the obese vs. the non-obese groups. Serum sex hormone-binding globulin was positively associated with variables of cholesterol absorption, whereas blood glucose, serum insulin, and body mass index were associated with variables of cholesterol synthesis. In multiple stepwise regression analysis, cholesterol absorption percentage (R2 = 24%) and body mass index (R2 = 15%) were the only variables explaining the variability of cholesterol synthesis.. Body weight, through its entire range, regulates cholesterol metabolism in type 2 diabetes such that with increasing insulin resistance, cholesterol absorption is lowered and cholesterol synthesis increased.

Topics: Absorption; Bile Acids and Salts; Blood Glucose; Body Mass Index; Body Weight; Cholestanol; Cholesterol; Diabetes Mellitus; Diabetes Mellitus, Type 2; Feces; Female; Humans; Insulin; Lipids; Lipoproteins; Male; Middle Aged; Obesity; Phytosterols; Regression Analysis; Sex Hormone-Binding Globulin; Sterols

Ca may interfere with fat and cholesterol metabolism through formation of insoluble soaps with fatty and bile acids in the intestine. In the present study, we examined the effects of different dietary Ca levels on the serum lipid profile and cholesterol metabolism in obese Zucker rats fed a low-fat diet. We also tested whether dietary Ca interfered with the lipid-lowering effects of a pine oil-derived plant sterol mixture. Increase in dietary Ca intake from 0.2 to 0.8%, and further to 2.1% (w/w) dose-dependently decreased serum total cholesterol (r -0.565, P=0.002, n 27), LDL-cholesterol (r -0.538, P=0.006, n 25), and triacylglycerol (r -0.484, P=0.014, n 25) concentrations, and increased HDL-cholesterol (r -0.478, P=0.016, n 25) and HDL: LDL cholesterol (r 0.672, P<0.001, n 25) in rats fed a 1% cholesterol diet. Analysis of serum campesterol: cholesterol and sitosterol: cholesterol suggested that Ca dose-dependently increased intestinal cholesterol absorption (r 0.913, P<0.001, n 18), whereas serum desmosterol: cholesterol and lathosterol: cholesterol indicated that Ca dose-dependently increased endogenous cholesterol synthesis (r 0.691, P=0.003, n 18). Therefore, the decrease of serum LDL-cholesterol appeared to be due to Ca-induced increase in the conversion of cholesterol to bile acids. The increase in Ca intake did not interfere with the beneficial effects of plant sterols on serum total cholesterol, LDL-cholesterol and HDL-cholesterol concentrations. The high-Ca diet with plant sterol supplementation further increased the HDL-cholesterol concentration and HDL: LDL cholesterol. The present findings indicate that the beneficial effects of dietary Ca on the serum lipid profile during a low-fat diet are dose-dependent, and resemble those of bile acid sequestrants. Increased dietary Ca did not impede the lipid-lowering effects of natural plant sterols.

Topics: Animals; Calcium, Dietary; Cholesterol, Dietary; Dietary Fats; Dose-Response Relationship, Drug; Female; Intestinal Absorption; Lipids; Obesity; Phytosterols; Rats; Rats, Zucker

Recent clinical studies have demonstrated that plant sterols moderately lower serum cholesterol levels in patients with mild hypercholesterolemia. Furthermore, there is evidence suggesting that mineral nutrients, such as calcium and magnesium, may also decrease serum cholesterol concentrations. In this study, we tested the hypothesis that supplementation with mineral nutrients may enhance the cholesterol-lowering effect of plant sterols in obese Zucker rats. Furthermore, we compared the lipid-lowering effects of monovalent sodium and potassium cations with those of divalent calcium and magnesium cations.. A Western-type high-fat/high-cholesterol diet increased serum cholesterol by 175% and liver cholesterol by 65% in comparison with a low-fat/low-cholesterol control diet. On the contrary, the high-fat/high-cholesterol diet decreased intestinal cholesterol absorption, as assessed by means of serum campesterol-, sitosterol-, and sitostanol-to-cholesterol ratios, thus indicating that it was under negative feedback regulation. Supplementation of the high-fat/high-cholesterol diet with plant sterols or mineral nutrients partially prevented the diet-induced increased in serum cholesterol and, when given concurrently, their cholesterol-lowering effect was enhanced. Their combination also effectively prevented the diet-induced increase in liver cholesterol concentration, and had beneficial effects on liver and myocardial hypertrophy, and the development of obesity. These beneficial effects were at least partially mediated by an enhanced blockade of intestinal cholesterol absorption. Interestingly, only divalent cations enhanced the cholesterol-lowering effect of plant sterols, thus supporting the idea that the lipid-lowering effect of divalent cations is related to the formation of insoluble and inabsorbable calcium and magnesium chelates with fatty acids.. Our findings indicate that the cholesterol-lowering effect of plant sterols is enhanced by the co-administration of divalent calcium and magnesium cations but not by monovalent sodium and potassium cations.

Topics: Analysis of Variance; Animals; Calcium, Dietary; Cholesterol; Electrolytes; Female; Lipid Metabolism; Magnesium; Obesity; Phytosterols; Potassium, Dietary; Rats; Rats, Zucker; Sodium, Dietary

Role of enterohepatic cholesterol metabolism in obesity-induced increase of cholesterol synthesis was studied in healthy lean (BMI <24) and overweight (BMI >31) subjects by measuring serum lipids (including plant sterols, cholestanol and cholesterol precursors), cholesterol absorption % (double-label method), sterol balance and biliary lipids. New aspects of sterol metabolism in obesity were as follows: low efficiency of cholesterol absorption, reduced ratios to cholesterol of serum and biliary plant sterols and cholestanol (5alpha-derivative of cholesterol), and a marked increase of serum and biliary cholesterol precursor sterols. Percent of cholesterol absorption was positively related to serum cholestanol and plant sterols, and negatively to cholesterol synthesis, measured by the sterol balance technique or cholesterol precursor sterols in serum or bile. Total and endogenous cholesterol fluxes into the intestine were increased, but owing to low absorption percent, mass of cholesterol absorption was within control limits in the obese subjects. Thus, per gram of their large liver tissue the entry of intestinal cholesterol may even be subnormal. Percent of cholesterol absorption was insignificantly negatively (r=-0.256) related to intestinal cholesterol pool, but significantly to biliary concentrations of cholesterol (r=-0.581), bile acids (r=-0.513) and phospholipids (r=-0.469). Thus, dilution of labeled dietary cholesterol by expanded intestinal cholesterol pool could have contributed to subnormal efficiency of cholesterol absorption, or transfer of labeled dietary cholesterol from intestinal oil phase to micellar phase may be competitively inhibited by expanded biliary secretion, resulting in reduced absorption of dietary cholesterol. These mechanisms could have contributed to changes in metabolism of non-cholesterol sterols, especially of cholestanol and plant sterols.

Topics: Bile; Cholesterol; Feces; Humans; Intestinal Absorption; Intestinal Mucosa; Lipid Metabolism; Lipids; Male; Middle Aged; Obesity; Phytosterols; Reference Values; Sterols

Topics: Arteriosclerosis; Bile; Bile Acids and Salts; Cholelithiasis; Cholesterol; Cholesterol, Dietary; Diet; Diet Therapy; Dietary Fats; Fasting; Fats, Unsaturated; Fatty Acids, Unsaturated; Humans; Male; Obesity; Phytosterols