Estrogen receptor 1 gene polymorphisms in premenopausal women: interaction between genotype and smoking on lipid levels

Estrogen has multiple effects on lipid and lipoprotein metabolism. We investigated the association between the four common single nucleotide polymorphisms in the estrogen receptor 1 (ESR1) gene locus, -1989T>G, +261G>C, IVS1-397T>C and IVS1-351A>G, and lipid and lipoprotein levels in southern Brazilians. The sample consisted in 150 men and 187 premenopausal women. The women were considered premenopausal if they had regular menstrual bleeding within the previous 3 months and were 18-50 years of age. Exclusion criteria were pregnancy, secondary hyperlipidemia due to renal, hepatic or thyroid disease, and diabetes. Smoking status was self-reported; subjects were classified as never smoked and current smokers. DNA was amplified by PCR and was subsequently digested with the appropriate restriction enzymes. Statistical analysis was carried out for men and women separately. In the study population, major allele frequencies were _1989*T (0.83), +261*G (0.96), IVS1-397*T (0.58), and IVS1-351*A (0.65). Multiple linear regression analyses indicated that an interaction between +261G>C polymorphism and smoking was a significant factor affecting high-density lipoprotein cholesterol (HDL-C) levels (P = 0.028) in women. Nonsmoking women with genotype G/C of +261G>C polymorphism had mean HDL-C levels higher than those with G/G genotype (1.40 ± 0.33 vs 1.22 ± 0.26 mmol/L; P = 0.033). No significant associations with lipid and lipoprotein levels in women and men were detected for other polymorphisms. In conclusion, the +261G>C polymorphism might influence lipoprotein and lipid levels in premenopausal women, but these effects seem to be modulated by smoking, whereas in men ESR1 polymorphisms were not associated with high lipoprotein levels.

Effect of a cholesterol-rich diet on the metabolism of the free and esterified cholesterol components of a nanoemulsion that resembles LDL in rabbits

We have shown that the free cholesterol (FC) and the cholesteryl ester (CE) moieties of a nanoemulsion with lipidic structure resembling low-density lipoproteins show distinct metabolic fate in subjects and that this may be related to the presence of dyslipidemia and atherosclerosis. The question was raised whether induction of hyperlipidemia and atherosclerosis in rabbits would affect the metabolic behavior of the two cholesterol forms. Male New Zealand rabbits aged 4-5 months were allocated to a control group (N = 17) fed regular chow and to a 1% cholesterol-fed group (N = 13) during a 2-month period. Subsequently, the nanoemulsion labeled with ³H-FC and 14C-CE was injected intravenously for the determination of plasma kinetics and tissue uptake of the radioactive labels. In controls, FC and CE had similar plasma kinetics (fractional clearance rate, FCR = 0.234 ± 0.056 and 0.170 ± 0.038 h-1, respectively; P = 0.065). In cholesterol-fed rabbits, the clearance of both labels was delayed and, as a remarkable feature, FC-FCR (0.089 ± 0.033 h-1) was considerably greater than CE-FCR (0.046 ± 0.010 h-1; P = 0.026). In the liver, the major nanoemulsion uptake site, uptake of the labels was similar in control animals (FC = 0.2256 ± 0.1475 and CE = 0.2135 ± 0.1580%/g) but in cholesterol-fed animals FC uptake (0.0890 ± 0.0319%/g) was greater than CE uptake (0.0595 ± 0.0207%/g; P < 0.05). Therefore, whereas in controls, FC and CE have similar metabolism, the induction of dyslipidemia and atherosclerosis resulted in dissociation of the two forms of cholesterol.

Normal flow-mediated vasodilatation of the brachial artery and carotid artery intima-media thickness in subclinical hypothyroidism

Subclinical hypothyroidism (SHT) is a disease for which exact therapeutic approaches have not yet been established. Previous studies have suggested an association between SHT and coronary heart disease. Whether this association is related to SHT-induced changes in serum lipid levels or to endothelial dysfunction is unclear. The aim of this study was to determine endothelial function measured by the flow-mediated vasodilatation of the brachial artery and the carotid artery intima-media thickness (IMT) in a group of women with SHT compared with euthyroid subjects. Triglycerides, total cholesterol, HDL-C, LDL-C, apoprotein A (apo A), apo B, and lipoprotein(a) were also determined. Twenty-one patients with SHT (mean age: 42.4 ± 10.8 years and mean thyroid-stimulating hormone (TSH) levels: 8.2 ± 2.7 µIU/mL) and 21 euthyroid controls matched for body mass index, age and atherosclerotic risk factors (mean age: 44.2 ± 8.5 years and mean TSH levels: 1.4 ± 0.6 µIU/mL) participated in the study. Lipid parameters (except HDL-C and apo A, which were lower) and IMT values were higher in the common carotid and carotid bifurcation of SHT patients with positive serum thyroid peroxidase antibodies (TPO-Ab) (0.62 ± 0.2 and 0.62 ± 0.16 mm for the common carotid and carotid bifurcation, respectively) when compared with the negative TPO-Ab group (0.55 ± 0.24 and 0.58 ± 0.13 mm, for common carotid and carotid bifurcation, respectively). The difference was not statistically significant. We conclude that minimal thyroid dysfunction had no adverse effects on endothelial function in the population studied. Further investigation is warranted to assess whether subclinical hypothyroidism, with and without TPO-Ab-positive serology, has any effect on endothelial function.

Prevalence of metabolic syndrome and its association with educational inequalities among Brazilian adults: a population-based study

The present study estimated the prevalence of metabolic syndrome (MS) according to the criteria established by the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII) and the International Diabetes Federation (IDF) and analyzed the contribution of social factors in an adult urban population in the Southeastern region of Brazil. The sample plan was based on multistage probability sampling according to family head income and educational level. A random sample of 1116 subjects aged 30 to 79 years was studied. Participants answered a questionnaire about socio-demographic variables and medical history. Fasting capillary glucose (FCG), total cholesterol, high-density lipoprotein cholesterol (HDL-C), and triglycerides were determined and all non-diabetic subjects were submitted to the 75-g oral glucose tolerance test. Body mass index (BMI, kg/m²), waist circumference and blood pressure (BP) were determined. Age- and gender-adjusted prevalence of MS was 35.9 and 43.2% according to NCEP-ATPIII and IDF criteria, respectively. Substantial agreement was found between NCEP-ATPIII and IDF definitions. Low HDL-C levels and high BP were the most prevalent MS components according to NCEP-ATPIII criteria (76.3 and 59.2%, respectively). Considering the diagnostic criteria adopted, 13.5% of the subjects had diabetes and 9.7% had FCG ≥100 mg/dL. MS prevalence was significantly associated with age, skin color, BMI, and educational level. This cross-sectional population-based study in the Southeastern region of Brazil indicates that MS is highly prevalent and associated with an important social indicator, i.e., educational level. This result suggests that in developing countries health policy planning to reduce the risk of MS, in particular, should consider improvement in education.

Differences in synthesis and absorption of cholesterol of two effective lipid-lowering therapies

Effective statin therapy is associated with a marked reduction of cardiovascular events. However, the explanation for full benefits obtained for LDL cholesterol targets by combined lipid-lowering therapy is controversial. Our study compared the effects of two equally effective lipid-lowering strategies on markers of cholesterol synthesis and absorption. A prospective, open label, randomized, parallel design study, with blinded endpoints, included 116 subjects. We compared the effects of a 12-week treatment with 40 mg rosuvastatin or the combination of 40 mg simvastatin/10 mg ezetimibe on markers of cholesterol absorption (campesterol and β-sitosterol), synthesis (desmosterol), and their ratios to cholesterol. Both therapies similarly decreased total and LDL cholesterol, triglycerides and apolipoprotein B, and increased apolipoprotein A1 (P < 0.05 vs baseline for all). Simvastatin/ezetimibe increased plasma desmosterol (P = 0.012 vs baseline), and decreased campesterol and β-sitosterol (P < 0.0001 vs baseline for both), with higher desmosterol (P = 0.007) and lower campesterol and β-sitosterol compared to rosuvastatin, (P < 0.0001, for both). In addition, rosuvastatin increased the ratios of these markers to cholesterol (P < 0.002 vs baseline for all), whereas simvastatin/ezetimibe significantly decreased the campesterol/cholesterol ratio (P = 0.008 vs baseline) and tripled the desmosterol/cholesterol ratio (P < 0.0001 vs baseline). The campesterol/cholesterol and β-sitosterol/cholesterol ratios were lower, whereas the desmosterol/cholesterol ratio was higher in patients receiving simvastatin/ezetimibe (P < 0.0001 vs rosuvastatin, for all). Pronounced differences in markers of cholesterol absorption and synthesis were observed between two equally effective lipid-lowering strategies.

Effects of rosiglitazone on serum paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus

Human serum paraoxonase contributes to the anti-atherogenic effect of high-density lipoprotein cholesterol (HDL-C) and has been shown to protect both low-density lipoprotein cholesterol (LDL-C) and HDL-C against lipid peroxidation. We investigated the effects of rosiglitazone on paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus [50 patients (30 males, 20 females); mean±SD age: 58.7±9.2 years, body mass index: 28.2±4.1'kg/m2], in whom glucose control could not be achieved despite treatment with metformin, sulphonylurea, and/or insulin. The patients were given 4'mg/day rosiglitazone for 3 months in addition to their usual treatment. Serum paraoxonase activity, malondialdehyde, homocysteine, and lipid profile were measured at the time of initiation and at the end of therapy with rosiglitazone. After rosiglitazone therapy, serum levels of HDL-C, apolipoprotein A-1, and paraoxonase activity increased significantly (P<0.05) and malondialdehyde, homocysteine, lipoprotein(a), and glucose levels decreased significantly (P<0.05), but no significant changes in levels of total cholesterol and apolipoprotein B were observed. Triglyceride levels also increased significantly (P<0.05). Rosiglitazone treatment led to an improvement in glycemic control and to an increase in paraoxonase activity and HDL-C levels. Although rosiglitazone showed favorable effects on oxidant/antioxidant balance and lipid profile, further studies are needed to determine the effect of rosiglitazone on cardiovascular risk factors and cardiovascular morbidity and mortality.

Association of adult weight gain and nonalcoholic fatty liver in a cross-sectional study in Wan Song Community, China

Our objective was to examine associations of adult weight gain and nonalcoholic fatty liver disease (NAFLD). Cross-sectional interview data from 844 residents in Wan Song Community from October 2009 to April 2010 were analyzed in multivariate logistic regression models to examine odds ratios (OR) and 95% confidence intervals (CI) between NAFLD and weight change from age 20. Questionnaires, physical examinations, laboratory examinations, and ultrasonographic examination of the liver were carried out. Maximum rate of weight gain, body mass index, waist circumference, waist-to-hip ratio, systolic blood pressure, diastolic blood pressure, fasting blood glucose, cholesterol, triglycerides, uric acid, and alanine transaminase were higher in the NAFLD group than in the control group. HDL-C in the NAFLD group was lower than in the control group. As weight gain increased (measured as the difference between current weight and weight at age 20 years), the OR of NAFLD increased in multivariate models. NAFLD OR rose with increasing weight gain as follows: OR (95%CI) for NAFLD associated with weight gain of 20+ kg compared to stable weight (change <5 kg) was 4.23 (2.49-7.09). Significantly increased NAFLD OR were observed even for weight gains of 5-9.9 kg. For the “age 20 to highest lifetime weight” metric, the OR of NAFLD also increased as weight gain increased. For the “age 20 to highest lifetime weight” metric and the “age 20 to current weight” metric, insulin resistance index (HOMA-IR) increased as weight gain increased (P<0.001). In a stepwise multivariate regression analysis, significant association was observed between adult weight gain and NAFLD (OR=1.027, 95%CI=1.002-1.055, P=0.025). We conclude that adult weight gain is strongly associated with NAFLD.

Cardiorespiratory fitness, pulmonary function and C-reactive protein levels in nonsmoking individuals with diabetes

The objective of this study was to evaluate cardiorespiratory fitness and pulmonary function and the relationship with metabolic variables and C-reactive protein (CRP) plasma levels in individuals with diabetes mellitus (DM). Nineteen men with diabetes and 19 age- and gender-matched control subjects were studied. All individuals were given incremental cardiopulmonary exercise and pulmonary function tests. In the exercise test, maximal workload (158.3±22.3vs 135.1±25.2, P=0.005), peak heart rate (HRpeak: 149±12 vs 139±10, P=0.009), peak oxygen uptake (VO2peak: 24.2±3.2 vs18.9±2.8, P<0.001), and anaerobic threshold (VO2VT: 14.1±3.4 vs 12.2±2.2, P=0.04) were significantly lower in individuals with diabetes than in control subjects. Pulmonary function test parameters, blood pressure, lipid profile (triglycerides, HDL, LDL, and total cholesterol), and CRP plasma levels were not different in control subjects and individuals with DM. No correlations were observed between hemoglobin A1C (HbA1c), CRP and pulmonary function test and cardiopulmonary exercise test performance. In conclusion, the results demonstrate that nonsmoking individuals with DM have decreased cardiorespiratory fitness that is not correlated with resting pulmonary function parameters, HbA1c, and CRP plasma levels.

Beneficial effects of Ginkgo biloba extract on insulin signaling cascade, dyslipidemia, and body adiposity of diet-induced obese rats

Ginkgo biloba extract (GbE) has been indicated as an efficient medicine for the treatment of diabetes mellitus type 2. It remains unclear if its effects are due to an improvement of the insulin signaling cascade, especially in obese subjects. The aim of the present study was to evaluate the effect of GbE on insulin tolerance, food intake, body adiposity, lipid profile, fasting insulin, and muscle levels of insulin receptor substrate 1 (IRS-1), protein tyrosine phosphatase 1B (PTP-1B), and protein kinase B (Akt), as well as Akt phosphorylation, in diet-induced obese rats. Rats were fed with a high-fat diet (HFD) or a normal fat diet (NFD) for 8 weeks. After that, the HFD group was divided into two groups: rats gavaged with a saline vehicle (HFD+V), and rats gavaged with 500 mg/kg of GbE diluted in the saline vehicle (HFD+Gb). NFD rats were gavaged with the saline vehicle only. At the end of the treatment, the rats were anesthetized, insulin was injected into the portal vein, and after 90s, the gastrocnemius muscle was removed. The quantification of IRS-1, Akt, and Akt phosphorylation was performed using Western blotting. Serum levels of fasting insulin and glucose, triacylglycerols and total cholesterol, and LDL and HDL fractions were measured. An insulin tolerance test was also performed. Ingestion of a hyperlipidic diet promoted loss of insulin sensitivity and also resulted in a significant increase in body adiposity, plasma triacylglycerol, and glucose levels. In addition, GbE treatment significantly reduced food intake and body adiposity while it protected against hyperglycemia and dyslipidemia in diet-induced obesity rats. It also enhanced insulin sensitivity in comparison to HFD+V rats, while it restored insulin-induced Akt phosphorylation, increased IRS-1, and reduced PTP-1B levels in gastrocnemius muscle. The present findings suggest that G. biloba might be efficient in preventing and treating obesity-induced insulin signaling impairment.

Effect of gala apples (Malus domestica Borkh) on lipidemia of hyperlipidemic rats

A healthy life style and a balanced diet, associated with a high fruit and vegetable intake, are linked to good health and the prevention of diseases. Apples contain bioactive compounds that help in the prevention and control of hyperlipidemia. One of the Public Health concerns in Brazil is to reduce cardiovascular diseases. Therefore, the objective of this work was to analyze the chemical composition of Gala apples and to study the effect of their consumption on weight gain, food intake, serum levels of total cholesterol, HDL-C, LDL-C, triglycerides, hepatic cholesterol and fecal cholesterol in male albino Wistar rats fed a hypercholesterolemic diet. Six animals were utilized for each treatment (control, 5, 15 and 25% apple diet), during 30 and 60 days. This study showed that one apple (200 g) can provide 14.5% of recommended total fiber and 55% of recommended vitamin C, besides supplying considerable quantities of phenolic compounds (0.38 g.100 g-1) and tannins (0.16 g.100 g-1). All animals showed a non-significant reduction in their weight gain and food intake with an increase in the concentration of apple in the diets. At the end of 30 days, all of the diets provided a significant reduction in the levels of triglycerides compared to the control group. The 15 and 25% apple diets showed significant reductions in the serum levels of total cholesterol and LDL-C and an increase in the level of fecal cholesterol in relation to the control group. The 25% apple diet provided a significant reduction in the hepatic cholesterol levels compared to the control group. After 60 days, the serum levels of total cholesterol, LDL-C, HDL-C and triglycerides in rats fed with 5, 15 and 25% apple diets were similar to the control group. This probably happened due to a revertion of the process. These results show the importance of Gala apples in the control of hyperlipidemia in rats. A diet rich in vegetables and fruits, including apples, associated to a healthy life style, over time, could prevent or reduce the risk of heart disease.

Effects of grilling on cholesterol oxide formation and fatty acids alterations in fish

Due to the adverse effects of the cholesterol oxidation products for the human health, the search of the occurrence and the quantification of these compounds in foods are considered of great importance. In this paper the effect of grilling in hake and sardine on cholesterol oxides formation and fatty acids alterations was investigated. The main fatty acids determined in both fishes were docosahexaenoic (DHA), oleic, eicosapentaenoic (EPA) and palmitoleic. The total lipids, fatty acids and cholesterol contents were decreased significantly (p < 0.02) after thermal treatment, with simultaneous increase of the cholesterol oxides contents. The cholesterol oxides determined in both species in the present study were: 19-hydroxycholesterol, 24(S)-hydroxycholesterol, 22(S) hydroxycholesterol, 25-hydroxycholesterol, 25(R)-hydroxycholesterol and 7-ketocolesterol. Besides the presence of the cholesterol oxides in raw fishes, there were a greater number of products resulting from the oxidation of cholesterol side chain, a fact rarely observed in foods.

Fatty acids, cholesterol, oxidative rancidity, and color of irradiated shrimp

The effect of gamma irradiation (0, 2, 4, and 6 kGy doses) applied to frozen and packed headed shrimp on the fatty acid profile, cholesterol content, and lipid and color stability was evaluated. Myristic acid was higher in shrimp irradiated with 4 and 6 kGy and palmitic acid was higher in samples irradiated with 2 and 6 kGy compared to non-irradiated samples. Stearic and behenic acids were lower in shrimp irradiated with 6 kGy compared to non-irradiated shrimp. With regard to non-irradiated shrimp, palmitoleic, oleic, and linoleic acids and total monounsaturated fatty acids were higher in shrimp irradiated with 6 kGy. Saturated fatty acid and cholesterol contents in irradiated samples were not different from those in non-irradiated shrimp. Lipid oxidation was higher in samples irradiated with 2, 4, and 6 kGy. Redness and yellowness of cooked shrimp were higher in samples irradiated with 6 kGy than in those in non-irradiated samples. The application of irradiation in doses up to 6 kGy on frozen and packed headed shrimp does not affect negatively the fatty acid profile, cholesterol content, and lipid and color stability.

Effects of defatted amaranth (Amaranthus caudatus L.) snacks on lipid metabolism of patients with moderate hypercholesterolemia

We evaluated the effects of defatted amaranth (Amaranthus caudatus L.) snacks on plasma lipids in moderate hypercholesterolemic patients. Twenty-two subjects [30-65 years old), 11 males, with total cholesterol (TC) > 240 mg.dL-1, low-density cholesterol (LDL-c) 160-190 mg.dL-1 and plasma triglycerides (TG) < 400 mg.dL-1] were randomized in a double blind clinical trial to receive an amaranth snack (50 g/day) or equivalent corn snack (placebo) for 2 months. There were no differences between amaranth and placebo on TC and LDL-c, and TG respectively: -8.4 and -5.7% (p = 0.17); -12.3 and -9.7% (p = 0.41) and -0.6 and -7.3% (p = 0.47). However, amaranth snacks significantly reduced high-density cholesterol (HDL-c): -15.2 vs. -4% (p = 0.03). In conclusion, the intake of 50 g of extruded amaranth daily during 60 days did not significantly reduce LDL-c in moderate hypercholesterolemic subjects; furthermore there was a significant reduction in HDL-c. Studies with greater number of subjects and greater quantity of this food are necessary to test the effects of amaranth on lipid metabolism in humans.

Influence of food components on lipid metabolism: scenarios and perspective on the control and prevention of dyslipidemias

Cardiovascular diseases (CVD) are the main causes of death in the Western world. Among the risk factors that are modifiable by diet, for reducing cardiovascular disease risks, the total plasma concentrations of cholesterol, triglycerides, LDL-C, and HDL-C are the most important. Dietary measures can balance these components of the lipid profile thus reducing the risk of cardiovascular diseases. The main food components that affect the lipid profile and can be modified by diet are the saturated and trans fats, unsaturated fats, cholesterol, phytosterols, plant protein, and soluble fiber. A wealth of evidence suggests that saturated and trans fats and cholesterol in the diet raise the total plasma cholesterol and LDL-C. Trans fats also reduce HDL-C, an important lipoprotein for mediating the reverse cholesterol transport. On the other hand, phytosterols, plant proteins, isoflavones, and soluble fiber are protective diet factors against cardiovascular diseases by modulating plasma lipoprotein levels. These food components at certain concentrations are able to reduce the total cholesterol, TG, and LDL-C and raise the plasma levels of HDL-C. Therefore, diet is an important tool for the prevention and control of cardiovascular diseases, and should be taken into account as a whole, i.e., not only the food components that modulate plasma concentrations of lipoproteins, but also the diet content of macro nutrients and micronutrients should be considered.