Influência da atividade das mataloproteinases 2 e 9 na diminuiçao o colágeno tipo I miocárdico em ratos obesos

Pós-graduação em Fisiopatologia em Clínica Médica - FMB

Cryotolerance and global gene-expression patterns of Bos taurus indicus and Bos taurus taurus in vitro- and in vivo-produced blastocysts

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Aggravation of nonalcoholic steatohepatitis by moderate alcohol consumption is associated with decreased SIRT1 activity in rats

Chronic alcohol intake decreases adiponectin and sirtuin 1 (SIRT1) expressions, both of which have been implicated in various biological processes including inflammation, apoptosis and metabolism. We have previously shown that moderate consumption of alcohol aggravates liver inflammation and apoptosis in rats with pre-existing nonalcoholic steatohepatitis (NASH). This study investigated whether moderate alcohol intake alters SIRT1 activity, adiponectin/Adiponectin receptor (AdipoR)-related signaling and lipid metabolism in a pre-existing NASH status. Sprague-Dawley rats were fed with a high-fat diet (71% energy from fat) for 6 weeks to induce NASH then subsequently divided into 2 sub-groups: fed either a modified high-fat diet (HFD, 55% energy from fat) or a modified high-fat alcoholic diet (HFA, 55% energy from fat and 16% energy from ethanol) for an additional 4 weeks. We observed in comparison to HFD group, HFA increased hepatic nuclear SIRT1 protein but decreased its deacetylase activity. SREBP-1c protein expression and FAS mRNA levels were significantly upregulated, while DGAT1/2 and CPT-I mRNA levels were downregulated in the livers of HFA compared to HFD. Although hepatic AdipoR1 decreased, HFA did not alter AdipoR2 and their downstream signaling. There were no significant changes in plasma adiponectin and free fatty acids (FFA), as well as adiponectin expression in adipose tissue between the two groups. The present study indicates that suppression in SIRT1 deacetylase activity contributes to alcohol-exacerbated hepatic inflammation and apoptosis in rats with pre-existing NASH. In addition, moderate alcohol intake did not modulate adiponectin/AdipoR signaling axis in this model.

The relationship between inflammation, dyslipidemia and physical exercise: from the epidemiological to molecular approach

Dyslipidemia and inflammation are frequently found in some diseases, such as obesity, type 2 diabetes mellitus, and cancer cachexia. Recent literature has identified that lipids have a pivotal role in the activation of inflammatory pathways, increasing the production of inflammatory cytokines, mainly tumor necrosis factor alpha, interleukin 6 and 1β. On the other hand, cytokines can promote disruption of lipid metabolism, in special cholesterol reverse transport, which is linked to development of atherosclerosis. With this in mind, acute and chronic exercise trainings have been pointed as important tools to counteract both dyslipidemia symptoms and systemic inflammation. Moreover, physical activity has been recommended in the prevention/treatment of the above mentioned outcomes by important health organizations around the world, mainly because it costs less and generates fewer side effects than isolated medicine. Despite the well-documented capacity of acute and chronic exercise training to counteract sustained disease-related immunometabolism, we have chosen to take a look from a current perspective in molecular pathways and in the field of epidemiology. The aim of the present review was therefore to discuss the results of dyslipidemia and inflammatory conditions with acute and chronic exercise training, which underlies the field of molecular pathways and epidemiology. The mechanisms underlying the response to the treatment are considered.

Decaffeinated green tea extract rich in epigallocatechin-3-gallate improves insulin resistance and metabolic profiles in normolipidic diet--but not high-fat diet-fed mice

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

A genomewide association mapping study using ultrasound-scanned information identifies potential genomic regions and candidate genes affecting carcass traits in Nellore cattle

The aim of this study was to identify candidate genes and genomic regions associated with ultrasound-derived measurements of the rib-eye area (REA), backfat thickness (BFT) and rumpfat thickness (RFT) in Nellore cattle. Data from 640 Nellore steers and young bulls with genotypes for 290 863 single nucleotide polymorphisms (SNPs) were used for genomewide association mapping. Significant SNP associations were explored to find possible candidate genes related to physiological processes. Several of the significant markers detected were mapped onto functional candidate genes including ARFGAP3, CLSTN2 and DPYD for REA; OSBPL3 and SUDS3 for BFT; and RARRES1 and VEPH1 for RFT. The physiological pathway related to lipid metabolism (CLSTN2, OSBPL3, RARRES1 and VEPH1) was identified. The significant markers within previously reported QTLs reinforce the importance of the genomic regions, and the other loci offer candidate genes that have not been related to carcass traits in previous investigations.

Erva mate minimiza as alterações do perfil lipídico promovidas por elevado consumo de sacarose

The yerba mate (Ilex paraguariensis) is composed of bioactive that interfere with lipid metabolism. The objective was to evaluate if daily consumption of mate tea (MT) change the lipid deposits and dyslipidemia caused by excessive consumption of sucrose. Thirty male Wistar rats (40 days old) were divided into four groups: Group C - free access to commercial chow and deionized water; S - free access to commercial food, water and sucrose solution 30% (w/v) in water; MTS and deionized - free access to commercial feed solution, water, 30% sucrose (w/v) and treated with daily infusion of MT (soluble mate Leão Júnior®) via orogastric tube at a dose of 100 mg/kg/mc for 8 weeks. After the trial period the lipid profile was evaluated by the following parameters: a) direct weighing of the retroperitoneal (RP) and epididymal (EPI) adipose tissues; b) determination of plasma total cholesterol, triglycerides and HDL cholesterol concentration. The MT promoted the reduction of 1.4 times in both tissues RP and EPI in MTS group compared to group S. Treatment with MT decreased 2.7 times triglyceride in the MTS group compared with the group S. The sucrose consumption did not alter the plasma cholesterol concentration, however the consumption of MT significantly reduced total cholesterol circulating. The HDL cholesterol concentration, in the MTS group, showed higher concentration than in group S (1.3 times). MT prevents in young male rats the increase of lipid deposits and dyslipidemia caused by excessive consumption of sucrose.

Legumin from chickpea: hypolipidemic effect in the liver of hypercholesterolemic rats

Purpose – This paper aims to determine the effects of 11S globulin isolated from Chickpea (Cicer arietinum L.) on lipid metabolism in animals subjected to a hypercholesterolemic and hyperlipidemic diet and compared to the drug simvastatin. Design/methodology/approach – Thirty-six male Wistar rats, kept in individual cages and under appropriate conditions, were separated into groups that were fed a normal diet (STD) containing casein as protein source and according to AIN-93G; a high-cholesterol diet (HC), normal diet plus 1 per cent cholesterol and 0.5 per cent cholic acid and 20 per cent coconut oil; HC diet plus the isolated 11S globulin (300 mg/kg/day); and HC diet plus the simvastatin (50 mg/kg/day), both dissolved in saline and administered by gavage for 28 days. After this time, the animals were killed. Findings – The results indicated that the addition of 1 per cent cholesterol and 0.5 per cent cholic acid induced hypercholesterolemia in the animals without interfering with their weight gain. Analyses of total cholesterol (TC), HDL-cholesterol (HDL-C) and triglycerides (TG) in the plasma, and TC and TG in the liver were made. The results show that the protein isolated from chickpea, and given as a single daily dose, did not affect the levels of plasma TC and its fractions, although decreasing the TG levels. Unlike the simvastatin, the chickpea protein significantly reduced TC and TG in the liver relative to HC group. Originality/value – A single daily dose of 11S globulin from chickpea contributed as only as additional 2.8 per cent of dietary protein intake. These findings demonstrate that 11S chickpea protein acts as a functional agent in the lipid metabolism in addition to its nutritional properties.

One-hundred days of monitoring of patients undergoing hematopoietic stem cell transplantation: events of metabolic syndrome

Objective This study assessed early manifestations of metabolic syndrome determinants in patients submitted to hematopoietic stem cell transplantation. Methods Twenty-seven individuals participated in the study (20 with autologous and 7 with allogeneic hematopoietic stem cell transplantation). Anthropometric variables and biochemical indicators of lipid and glucose metabolism were determined before and 100 days after hematopoietic stem cell transplantation.Results The mean total cholesterol (p=0.086), very low density lipoprotein-cholesterol (p=0.069) and triglycerides (p=0.086) of all patients did not change significantly between the two study periods, but when the patients were separated by type of hematopoietic stem cell transplantation, triglycerides and very low density lipoprotein-cholesterol were close to the critical level of significance for individuals with allogeneic hematopoietic stem cell transplantation (p=0.060) and total cholesterol was significant in individuals with autologous hematopoietic stem cell transplantation (p=0.027). Anthropometric variables did not change significantly between before and 100 days after hematopoietic stem cell transplantation. Conclusion Metabolic syndrome risk factors may be associated with lipid metabolism in the early phase of allogeneic and autologous hematopoietic stem cell transplantation.

Drosophila melanogaster lipins are tissue-regulated and developmentally regulated and present specific subcellular distributions

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Adição de ácido linolênico e L-carnitina na maturação oocitária: efeitos sobre o metabolismo celular, potencial de desenvolvimento e criotolerância de embriões bovinos produzidos in vitro

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Fructose-Induced Hypothalamic AMPK Activation Stimulates Hepatic PEPCK and Gluconeogenesis due to Increased Corticosterone Levels

Fructose consumption causes insulin resistance and favors hepatic gluconeogenesis through mechanisms that are not completely understood. Recent studies demonstrated that the activation of hypothalamic 5'-AMP-activated protein kinase (AMPK) controls dynamic fluctuations in hepatic glucose production. Thus, the present study was designed to investigate whether hypothalamic AMPK activation by fructose would mediate increased gluconeogenesis. Both ip and intracerebroventricular (icv) fructose treatment stimulated hypothalamic AMPK and acetyl-CoA carboxylase phosphorylation, in parallel with increased hepatic phosphoenolpyruvate carboxy kinase (PEPCK) and gluconeogenesis. An increase in AMPK phosphorylation by icv fructose was observed in the lateral hypothalamus as well as in the paraventricular nucleus and the arcuate nucleus. These effects were mimicked by icv 5-amino-imidazole-4-carboxamide-1-beta-D-ribofuranoside treatment. Hypothalamic AMPK inhibition with icv injection of compound C or with injection of a small interfering RNA targeted to AMPK alpha 2 in the mediobasal hypothalamus (MBH) suppressed the hepatic effects of ip fructose. We also found that fructose increased corticosterone levels through a mechanism that is dependent on hypothalamic AMPK activation. Concomitantly, fructose-stimulated gluconeogenesis, hepatic PEPCK expression, and glucocorticoid receptor binding to the PEPCK gene were suppressed by pharmacological glucocorticoid receptor blockage. Altogether the data presented herein support the hypothesis that fructose-induced hypothalamic AMPK activation stimulates hepatic gluconeogenesis by increasing corticosterone levels. (Endocrinology 153: 3633-3645, 2012)

Intake, nutrient apparent digestibility and ruminal constituents of sheep fed diets with canola, sunflower or castor oils

The objective in this experiment was to determine the effects of feeding diets with canola, sunflower or castor oils on intake, nutrient apparent digestibility and ruminal constituents of crossbred Dorper x Santa Ines sheep. Four rumen-cannulated animals of 90.2 +/- 11.4 kg average body weight were assigned to a 4 x 4 latin square. Animals remained individually in cages for the metabolism assay and were fed diets containing roughage at 500 g/kg and concentrate based on ground corn and soybean meal also at 500 g/kg. No oil was added to the control diet, whereas the others had canola, sunflower or castor oils at 30 g/kg (DM basis). There was no difference for the intake of DM and nutrients, except for ether extract, which was greater when animals received oil. The digestibility coefficients of dry matter, organic matter, crude protein, non-fiber carbohydrates and neutral detergent fiber were not changed; however, the addition of oil increased the ether extract digestibility. The values of total digestible nutrients (TDN, g/kg of DM), digestible energy (DE, Mcal/kg of DM), TDN intake and DE intake also did not change with the addition of lipids. Concerning the ruminal constituents, the addition of vegetable oils reduced the concentrations of acetate, butyrate and total short-chain fatty acids. Adding canola, sunflower or castor oils at 30 g/kg in diets with 500 g roughage/kg and 500 g concentrate/kg does not impair the intake or digestibility of nutrients in sheep, although it reduces the concentration of short-chain fatty acids in the rumen.

Dyslipidemia: a prospective controlled randomized trial of intensive glycemic control in sepsis

Metabolic disturbances are quite common in critically ill patients. Glycemic control appears to be an important adjuvant therapy in such patients. In addition, disorders of lipid metabolism are associated with worse prognoses. The purpose of this study was to investigate the effects that two different glycemic control protocols have on lipid profile and metabolism. We evaluated 63 patients hospitalized for severe sepsis or septic shock, over the first 72 h of intensive care. Patients were randomly allocated to receive conservative glycemic control (target range 140-180 mg/dl) or intensive glycemic control (target range 80-110 mg/dl). Serum levels of low-density lipoprotein, high-density lipoprotein, triglycerides, total cholesterol, free fatty acids, and oxidized low-density lipoprotein were determined. In both groups, serum levels of low-density lipoprotein, high-density lipoprotein, and total cholesterol were below normal, whereas those of free fatty acids, triglycerides, and oxidized low-density lipoprotein were above normal. At 4 h after admission, free fatty acid levels were higher in the conservative group than in the intensive group, progressively decreasing in both groups until hour 48 and continuing to decrease until hour 72 only in the intensive group. Oxidized low-density lipoprotein levels were elevated in both groups throughout the study period. Free fatty acids respond to intensive glycemic control and, because of their high toxicity, can be a therapeutic target in patients with sepsis.

The I405V and Taq1B polymorphisms of the CETP gene differentially affect sub-clinical carotid atherosclerosis

Background: Cholesteryl ester transfer protein (CETP) plays a major role in lipid metabolism, but studies on the association of CETP polymorphisms with risks of cardiovascular disease are inconsistent. This study investigated whether the CETP gene I405V and Taq1B polymorphisms modified subclinical atherosclerosis in an asymptomatic Brazilian population sample. Methods: The polymorphisms were analyzed using polymerase chain reaction in 207 adult volunteers. Serum lipid profiles, oxLDL Ab titers, C-reactive protein and tumor necrosis factor-a concentrations and CETP and phospholipid transfer protein (PLTP) activities were determined, and common carotid artery intima-media thickness (cIMT) was measured using ultrasonography. Results: No differences in cIMT were observed between the presence or absence of the minor B2 and V alleles in either polymorphism. However, inverse correlations between mean cIMT and CETP activity in the presence of these polymorphisms were observed, and positive correlations of these polymorphisms with PLTP activity and oxLDL Ab titers were identified. Moreover, logistic multivariate analysis revealed that the presence of the B2 allele was associated with a 5.1-fold (CI 95%, OR: 1.26 - 21.06) increased risk for cIMT, which was equal and above the 66th percentile and positively interacted with age. However, no associations with the V allele or CETP and PLTP activities were observed. Conclusions: None of the studied parameters, including CETP activity, explained the different relationships between these polymorphisms and cIMT, suggesting that other non-determined factors were affected by the genotypes and related to carotid atherosclerotic disease.