Expression of caveolin-1 enhances cholesterol efflux in hepatic cells

HepG2 cells were stably transfected with human caveolin-1 (HepG2/cav cells). Transfection resulted in expression of caveolin-1 mRNA, a high abundance of caveolin-1 protein, and the formation of caveolae on the plasma membrane. Cholesterol efflux from HepG2/cav cells was 280 and 45% higher than that from parent HepG2 cells when human plasma and human apoA-I, respectively, were used as acceptors. The difference in efflux was eliminated by treatment of cells with progesterone. There was no difference in cholesterol efflux to cyclodextrin. Cholesterol efflux from plasma membrane vesicles was similar for the two cell types. Transfection led to a 40% increase in the amount of plasma membrane cholesterol in cholesterol-rich domains ( caveolae and/or rafts) and a 67% increase in the rate of cholesterol trafficking from intracellular compartments to these domains. Cholesterol biosynthesis in HepG2/cav cells was increased by 2-fold, and cholesterol esterification was reduced by 50% compared with parent HepG2 cells. The proliferation rate of transfected cells was significantly lower than that of non-transfected cells. Transfection did not affect expression of ABCA1 or the abundance of ABCA1 protein, but decreased secretion of apoA-I. We conclude that overexpression of caveolin-1 in hepatic cells stimulates cholesterol efflux by enhancing transfer of cholesterol to cholesterol-rich domains in the plasma membrane.

ROR alpha regulates the expression of genes involved in lipid homeostasis in skeletal muscle cells - Caveolin-3 and CPT-1 are direct targets of ROR

The staggerer mice carry a deletion in the RORalpha gene and have a prolonged humoral response, overproduce inflammatory cytokines, and are immunodeficient. Furthermore, the staggerer mice display lowered plasma apoA-I/-II, decreased plasma high density lipoprotein cholesterol and triglycerides, and develop hypo-alpha-lipoproteinemia and atherosclerosis. However, relatively little is known about RORalpha in the context of target tissues, target genes, and lipid homeostasis. For example, RORalpha is abundantly expressed in skeletal muscle, a major mass peripheral tissue that accounts for similar to40% of total body weight and 50% of energy expenditure. This lean tissue is a primary site of glucose disposal and fatty acid oxidation. Consequently, muscle has a significant role in insulin sensitivity, obesity, and the blood-lipid profile. In particular, the role of RORalpha in skeletal muscle metabolism has not been investigated, and the contribution of skeletal muscle to the ROR-/- phenotype has not been resolved. We utilize ectopic dominant negative RORalpha expression in skeletal muscle cells to understand the regulatory role of RORs in this major mass peripheral tissue. Exogenous dominant negative RORalpha expression in skeletal muscle cells represses the endogenous levels of RORalpha and -gamma mRNAs and ROR-dependent gene expression. Moreover, we observed attenuated expression of many genes involved in lipid homeostasis. Furthermore, we show that the muscle carnitine palmitoyltransferase-1 and caveolin-3 promoters are directly regulated by ROR and coactivated by p300 and PGC-1. This study implicates RORs in the control of lipid homeostasis in skeletal muscle. In conclusion, we speculate that ROR agonists would increase fatty acid catabolism in muscle and suggest selective activators of ROR may have therapeutic utility in the treatment of obesity and atherosclerosis.

The relative benefits of endurance and strength training on the metabolic factors and muscle function of people with type 2 diabetes mellitus

Objective: To compare the effects of a 4-month strength training (ST) versus aerobic endurance training (ET) program on metabolic control, muscle strength, and cardiovascular endurance in subjects with type 2 diabetes mellitus (T2D). Design: Randomized controlled trial. Setting: Large public tertiary hospital. Participants: Twenty-two T21) participants (I I men, I I women; mean age +/- standard error, 56.2 +/- 1.1 y; diabetes duration, 8.8 +/- 3.5y) were randomized into a 4-month ST program and 17 T2D participants (9 men, 8 women; mean age, 57.9 +/- 1.4y; diabetes duration, 9.2 +/- 1.7y) into a 4-month ET program. Interventions: ST (up to 6 sets per muscle group per week) and ET (with an intensity of maximal oxygen consumption of 60% and a volume beginning at 15min and advancing to a maximum of 30min 3X/wk) for 4 months. Main Outcome Measures: Laboratory tests included determinations of blood glucose, glycosylated hemoglobin (Hb A(1c)), insulin, and lipid assays. Results: A significant decline in Hb A, was only observed in the ST group (8.3% +/- 1.7% to 7.1% +/- 0.2%, P=.001). Blood glucose (204 +/- 16mg/dL to 147 +/- 8mg/dL, P <.001) and insulin resistance (9.11 +/- 1.51 to 7.15 +/- 1.15, P=.04) improved significantly in the ST group, whereas no significant changes were observed in the ET group. Baseline levels of total cholesterol (207 +/- 8mg/dL to 184 +/- 7mg/dL, P <.001), low-density lipoprotein cholesterol (120 +/- 8mg/dL to 106 +/- 8mg/dL, P=.001), and triglyceride levels (229 +/- 25mg/dL to 150 +/- 15mg/dL, P=.001) were significantly reduced and high-density lipoprotein cholesterol (43 +/- 3mg/dL to 48 +/- 2mg/dL, P=.004) was significantly increased in the ST group; in contrast, no such changes were seen in the ET group. Conclusions: ST was more effective than ET in improving glycemic control. With the added advantage of an improved lipid profile, we conclude that ST may play an important role in the treatment of T2D.

Berberine - a novel approach to cholesterol lowering

Although low-density lipoprotein (LDL)-cholesterol lowering with the statins reduces the mortality and morbidity associated with coronary artery disease, considerable mortality and morbidity remains. Berberine upregulates the LDL receptor (LDLR) by a mechanism distinct from that of the statins, which involves stabilising the LDLR mRNA. In hamsters fed a high-fat and high-cholesterol diet for 2 weeks, the oral administration of berberine 100 mg/kg for 10 days reduced total serum cholesterol from &SIM; 4.8 to 2.7 mmol/l, and LDL-cholesterol from &SIM; 2.5 to 1.4 mmol/l. In subjects with hypercholesterolaemia, berberine hydrochloride (0.5 g b.i.d. for 3 months) reduced LDL-cholesterol (from 3.2 to 2.4 mmol/l) without any effect on high-density lipoprotein-cholesterol. Berberine also caused a reduction in triglyceride levels from 2.3 to 1.5 mmol/l. As berberine and statins both upregulate LDLR, their lipid-lowering profiles are similar. Thus, this mechanism is unlikely to make berberine an attractive alternative to statins for lipid lowering in most circumstances. However, the other effects of berberine (anti hypertensive, inotropic and class III antiarrhythmic properties) may make it a useful agent in the treatment of cardiovascular disease.

White blood cell count predicts reduction in coronary heart disease mortality with pravastatin

Background-Elevated serum inflammatory marker levels are associated with a greater long-term risk of cardiovascular events. Because 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitors (statins) may have an antiinflammatory action, it has been suggested that patients with elevated inflammatory marker levels may have a greater reduction in cardiovascular risk with statin treatment. Methods and Results-We evaluated the association between the white blood cell count (WBC) and coronary heart disease mortality during a mean follow-up of 6.0 years in the Long-Term Intervention With Pravastatin in Ischemic Disease (LIPID) Study, a clinical trial comparing pravastatin (40 mg/d) with a placebo in 9014 stable patients with previous myocardial infarction or unstable angina. An increase in baseline WBC was associated with greater coronary heart disease mortality in patients randomized to placebo (hazard ratio for 1 X 10(9)/L increase in WBC, 1.18; 95% CI, 1.12 to 1.25; P<0.001) but not pravastatin (hazard ratio, 1.02; 95% CI, 0.96 to 1.09; P=0.56; P for interaction=0.004). The numbers of coronary heart disease deaths prevented per 1000 patients treated with pravastatin were 0, 9, 30, and 38 for baseline WBC quartiles of <5.9, 6.0 to 6.9, 7.0 to 8.1, and >8.2X10(9)/L, respectively. WBC was a stronger predictor of this treatment benefit than the ratio of total to high-density lipoprotein cholesterol and a global measure of cardiac risk. There was also a greater reduction (P=0.052) in the combined incidence of cardiovascular mortality, nonfatal myocardial infarction, and stroke with pravastatin as baseline WBC increased ( by quartile: 3, 41, 61, and 60 events prevented per 1000 patients treated, respectively). Conclusions-These data support the hypothesis that individuals with evidence of inflammation may obtain a greater benefit from statin therapy.

Rev-erb beta regulates the expression of genes involved in lipid absorption in skeletal muscle cells - Evidence for cross-talk between orphan nuclear receptors and myokines

Rev-erbbeta is an orphan nuclear receptor that selectively blocks trans-activation mediated by the retinoic acid-related orphan receptor-alpha (RORalpha). RORalpha has been implicated in the regulation of high density lipoprotein cholesterol, lipid homeostasis, and inflammation. Rev-erbbeta and RORalpha are expressed in similar tissues, including skeletal muscle; however, the pathophysiological function of Rev-erbbeta has remained obscure. We hypothesize from the similar expression patterns, target genes, and overlapping cognate sequences of these nuclear receptors that Rev-erbbeta regulates lipid metabolism in skeletal muscle. This lean tissue accounts for > 30% of total body weight and 50% of energy expenditure. Moreover, this metabolically demanding tissue is a primary site of glucose disposal, fatty acid oxidation, and cholesterol efflux. Consequently, muscle has a significant role in insulin sensitivity, obesity, and the blood-lipid profile. We utilize ectopic expression in skeletal muscle cells to understand the regulatory role of Rev-erbbeta in this major mass peripheral tissue. Exogenous expression of a dominant negative version of mouse Rev-erbbeta decreases the expression of many genes involved in fatty acid/lipid absorption (including Cd36, and Fabp-3 and -4). Interestingly, we observed a robust induction (> 15-fold) in mRNA expression of interleukin-6, an exercise-induced myokine that regulates energy expenditure and inflammation. Furthermore, we observed the dramatic repression (> 20- fold) of myostatin mRNA, another myokine that is a negative regulator of muscle hypertrophy and hyperplasia that impacts on body fat accumulation. This study implicates Rev-erbbeta in the control of lipid and energy homoeostasis in skeletal muscle. In conclusion, we speculate that selective modulators of Rev-erbbeta may have therapeutic utility in the treatment of dyslipidemia and regulation of muscle growth.

Obesity Indicators by Race/Ethnicity for Diagnosis of Cardiometabolic Diseases for a US Representative Sample of Adults

Background: Obesity, a growing epidemic, is a preventable risk factor for cardiometabolic diseases. Obesity and cardiometabolic diseases affect Hispanics and African Americans more than non-Hispanic Caucasians. This study examined the relationship among race/ethnicity, obesity diagnostic measures (body mass index, waist circumference, subscapular and triceps skinfold thickness), and cardiometabolic risk factors (hyperglycemia, high, non-high-density lipoprotein cholesterol, low, high-density lipoprotein cholesterol, and hypertension) for adults across the United States. Methods: Using data from two-cycles of the National Health and Examination Survey (NHANES) 2007-2010, and accounting for the complex sample design, logistic regression models were conducted comparing obesity indicators in Mexican Americans, other Hispanics, and Black non-Hispanics, with White non-Hispanics and their associations with the presence of cardiometabolic diseases. Results: Differences by race/ethnicity were found for subscapular skinfold thickness and hyperglycemia. Waist circumference and subscapular skinfold were positively associated with the presence of hyperglycemia; dyslipidemia, and hypertension across race/ ethnicity, adjusting for age, gender, smoking, physical activity, education, income to poverty index, and health insurance. Race/ ethnicity did not influence the association of any obesity indicators with the tested cardiometabolic diseases. All obesity measures except triceps skinfold were associated with hyperglycemia. Conclusions: We suggest that subscapular skinfold thickness be considered as an inexpensive non-intrusive screening tool for cardiometabolic risk factors in an adult US population

Prevalence of the metabolic syndrome and its components in Brazilian women with polycystic ovary syndrome

SOARES, Elvira Maria Mafaldo et al. Prevalence of the metabolic syndrome and its components in Brazilian women with polycystic ovary syndrome. Fertility and Sterility, v.89, n.3, p.649-655, mar. 2008

Prevalence of the metabolic syndrome and its components in Brazilian women with polycystic ovary syndrome

SOARES, Elvira Maria Mafaldo et al. Prevalence of the metabolic syndrome and its components in Brazilian women with polycystic ovary syndrome. Fertility and Sterility, v.89, n.3, p.649-655, mar. 2008

Efeito sacietogênico de um novo inibidor de tripsina da paçoca do amendoim com aumento plasmático de colecistocinina (cck)

Obesity is increasing, reaching epidemic levels in many regions of the world. Studies have shown that consumption of peanuts influences on weight control and this influence may be due to the action of trypsin inhibitors sacietogênica that condition increased plasma colescistocinina (CCK). Moreover, the peanut has other health benefits, and these assignments are guaranteed to increase their production and consumption of several of its products, including the paçoca peanut. The aim of this study was to identify the presence of a trypsin inhibitor in paçoca peanut and evaluate its effect on food intake, weight gain and histomorphological changes in swiss mice (n = 8) and Wistar rats (n = 6). Experimental diets were prepared based on the AIN-93G and supplemented with tack or peanut trypsin inhibitor partially purified paçoca peanut (AHTI). After each treatment, the animals were anesthetized and euthanized, their bloods were collected by cardiac puncture for the determination of CCK and other biochemical parameters (glucose, triglycerides, total cholesterol, high density lipoprotein, low density lipoprotein, glutamic-pyruvic transaminase, glutamic oxaloacetic transaminase and albumin) and their pancreas removed for histologic and morphometric analysis. The supplementation with paçoca peanut and the AHTI showed a decrease of body weight gain and food intake in both mice and rats, due to the satiety, since the animals showed no evidence of impairment of nutritional status conditioned by consumption the AHTI. There were also observed biochemical or morphological important when compared with controls. However, AHTI led to increased secretion of CCK, a peptide sacietogênico. Thus, these results indicate that AHTI present in paçoca peanut, is able to enhance the secretion of plasma CCK and thereby reduce the weight gain associated with lower food intake of experimenta animals

Ação Sacietogênica de um inibidor de tripsina da semente de tamarindo (Tamarindus indica L.)

The seeds are excellent sources of proteinase inhibitors and have been highlighted owing to various applications. Among these applications are those in effect on food intake and weight gain that stand out because of the increasing number of obese individuals. This study evaluated the effects of trypsin inhibitor present in the seed of tamarind (Tamarindus indica L.) reduction in weight gain, biochemical and morphological alterations in Wistar rats. For this, we partially purified a trypsin inhibitor tamarind seed. This inhibitor, ITT2 at a concentration of 25 mg / kg body weight, over a period of 14 days was able to reduce food intake in rats (n = 6) by approximately 47%, causing a reduction in weight gain approximately 70% when compared with the control group. With the evaluation of the in vivo digestibility was demonstrated that the animals lost weight due to satiety, presented by the reduction of food intake, since there were significant differences between true digestibility for the control group (90.7%) and the group treated with inhibitor (89.88%). Additionally, we checked the deeds of ITT2 on biochemical parameters (glucose, triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein, glutamic-pyruvic transaminase, glutamic oxaloacetic transaminase, gamma glutamyl transferase albumin, globulin, total protein and C-reactive protein) and these, when assessed in the study groups showed no statistically significant variations. We also evaluate the histology of some organs, liver, stomach, intestine, and pancreas, and showed no changes. And to evaluate the effect of trypsin inhibitor on food intake due to the satiety is regulated by cholecystokinin (CCK) were measured plasma levels, and it was observed that the levels of CCK in animals receiving ITT2 were significantly higher ( 20 + 1.22) than in animals receiving only solution with casein (10.14 + 2.9) or water (5.92 + 1.15). Thus, the results indicate that the effect caused ITT2 satiety, reducing food intake, which in turn caused a reduction in weight gain in animals without causing morphological and biochemical changes, this effect caused by the elevation of plasma levels CCK

Hematobiochemical changes of lead Poisoning and amelioration with Coconut ( Cocos nucifera L.) Water in wistar albino rats

To determine the ameliorative effect of coconut water on haematobiochemical changes due to lead poisoning in wistar albino rats for six weeks, sixty rats were assigned to four groups. 0.10g/l of lead and 75ml coconut ( cocus nucifera l.) water were given orally for six weeks. The mean values of red blood cells, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, red blood cell distribution width and platelets (8.10±0.63(×106μl), 52.7±0.87(μm3), 17.9±0.56(pg), 34.73±0.65(g/dl), 17.90±0.67(%) and 670.00±42.22(×103μl) respectively) reduced in lead treated rats when compared with control mean values (8.41 ± 0.90(×106μl), 56.60 ± 1.55(μm3), 19.33 ± 0.82(pg), 34.93 ± 0.90(g/dl), 18.27 ± 0.73(%) and 818.33± 123.68(×103μl) respectively ) and these values increased in75ml coconut water only group and the group of 0.10g/l lead + 75ml coconut water except mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, and red blood cell distribution width of the 75ml coconut water only. The mean values of white blood cells, lymphocytes, total cholesterol, triglyceride, high density lipoprotein-cholesterol, low density lipoprotein-cholesterol, low density lipoprotein-cholesterol/high density lipoproteincholesterol and total cholesterol/high density lipoprotein-cholesterol increased (12.23±0.57(×103μl), 79.83±3.87(%), 64.66±6.01(mg/dl), 89.00±7.94(mg/dl), 22.67±6.93(mg/dl), 21.00±4.58(mg/dl), 1.29±0.62 and 3.36±0.83 respectively ) in the lead group when compared with mean values of control group (5.83±0.74(×103μl), 69.07±10.57(%), 54.00±4.04(mg/dl), 97.33±11.34(mg/dl), 20.00±3.06(mg/dl), 17.00±6.51(mg/dl), 0.97±0.41 and 2.87±0.55 respectively) but the mean values decreased when compared with the mean values of group of 75ml coconut water only and group of 0.10g/l lead + 75ml coconut water, except the mean values of high density lipoprotein-cholesterol. These results indicate that coconut water could ameliorate effects of lead toxicity

Prevalencia del síndrome metabólico en el adulto mayor en las parroquias urbanas del cantón Cuenca, 2015

Introducción: En la actualidad existe un incremento de la población adulta mayor en el Ecuador, donde las tres principales causas de muerte son: diabetes, enfermedades hipertensivas, enfermedades cerebrovasculares. Las mismas que se relacionan etiopatológicamente con el síndrome metabólico. Objetivo: Determinar la prevalencia del síndrome metabólico (SM) en adultos mayores en el cantón Cuenca, 2015. Método y materiales: Se trata de un estudio descriptivo, que se realizó en 387 adultos de ambos sexos mayores de 65 años, en las parroquias urbanas del cantón Cuenca. Se excluyó a los adultos mayores con deficiencia mental, alteraciones del estado de conciencia, impedimento físico o con evidencia de diabetes. Para el levantamiento de los datos se utilizó una encuesta y se realizó pruebas de glicemia en ayunas, colesterol, triglicéridos, lípidos de alta densidad (HDL, high density lipids) y medidas antropométricas, los datos obtenidos fueron analizados estadísticamente mediante EpiInfo, Microsoft Excel 2010 y el software SPSS, y se presentó mediante tablas y gráficos de estadística descriptiva de porcentajes y frecuencias. Resultados: La media de edad fue de 73 años, el 63.57% fueron mujeres y el 36.43% hombres y la mayoría 35.4% tenía un nivel de instrucción de primaria completa. La prevalencia del síndrome metabólico fue del 54.01%, en las mujeres 61.38% y en los hombres 41.13%, la mayoría entre 65 y 74 años con un 53.2% y un 58.14% con estudios incompletos. Según el IMC la mayoría de adultos mayores con SM tenían sobrepeso 49.72% y obesidad. El criterio ATP III más encontrado fue la obesidad abdominal 78.81%, seguido por la disminución sérica de colesterol HDL, 74.42% y presión arterial elevada, 48.32%.

Prevalencia del síndrome metabólico en el adulto mayor en las parroquias urbanas del cantón Cuenca, 2015

Introducción: En la actualidad existe un incremento de la población adulta mayor en el Ecuador, donde las tres principales causas de muerte son: diabetes, enfermedades hipertensivas, enfermedades cerebrovasculares. Las mismas que se relacionan etiopatológicamente con el síndrome metabólico. Objetivo: Determinar la prevalencia del síndrome metabólico (SM) en adultos mayores en el cantón Cuenca, 2015. Método y materiales: Se trata de un estudio descriptivo, que se realizó en 387 adultos de ambos sexos mayores de 65 años, en las parroquias urbanas del cantón Cuenca. Se excluyó a los adultos mayores con deficiencia mental, alteraciones del estado de conciencia, impedimento físico o con evidencia de diabetes. Para el levantamiento de los datos se utilizó una encuesta y se realizó pruebas de glicemia en ayunas, colesterol, triglicéridos, lípidos de alta densidad (HDL, high density lipids) y medidas antropométricas, los datos obtenidos fueron analizados estadísticamente mediante EpiInfo, Microsoft Excel 2010 y el software SPSS, y se presentó mediante tablas y gráficos de estadística descriptiva de porcentajes y frecuencias. Resultados: La media de edad fue de 73 años, el 63.57% fueron mujeres y el 36.43% hombres y la mayoría 35.4% tenía un nivel de instrucción de primaria completa. La prevalencia del síndrome metabólico fue del 54.01%, en las mujeres 61.38% y en los hombres 41.13%, la mayoría entre 65 y 74 años con un 53.2% y un 58.14% con estudios incompletos. Según el IMC la mayoría de adultos mayores con SM tenían sobrepeso 49.72% y obesidad. El criterio ATP III más encontrado fue la obesidad abdominal 78.81%, seguido por la disminución sérica de colesterol HDL, 74.42% y presión arterial elevada, 48.32%.

Metabolic syndrome and associated factors in a population-based sample of schoolchildren in Colombia: The FUPRECOL Study

In contrast to the definition of metabolic syndrome (MetS) in adults, there is no standard definition of MetS in pediatric populations. We aimed to assess the differences in the prevalence of MetS in children and adolescents aged 9–17 years in the city of Bogota (Colombia) using four different operational definitions for these age groups and to examine the associated variables. A total of 673 children and 1,247 adolescents attending public schools in Bogota (54.4% girls; age range 9–17.9 years) were included. The prevalence of MetS was determined by the definitions provided by the International Diabetes Federation (IDF) and three published studies by Cook et al., de Ferranti et al., and Ford et al. The prevalence of MetS was 0.3%, 6.3%, 7.8%, and 11.0% according to the IDF, Cook et al., Ford et al., and de Ferranti et al. definitions, respectively. The most prevalent components were low high-density lipoprotein cholesterol and high triglyceride levels, whereas the least prevalent components were abdominal obesity and hyperglycemia. Overall, the prevalence of MetS was higher in obese than in non-obese schoolchildren. In conclusion, MetS diagnoses in schoolchildren strongly depend on the definition chosen. These findings may be relevant to health promotion efforts for Colombian youth to develop prospective studies and to define which cut-offs are the best indicators of future morbidity.