JOSE TADEU STEFANO
Projetos de Pesquisa
Unidades Organizacionais
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina
10 resultados
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conferenceObject THE COMBINATION OF PROBIOTICS AND PREBIOTICS SUPPLEMENTATION IMPROVES LIPID METABOLISM, NAFLD AND OBESITY IN OB/OB MICE(2015) STEFANO, J. T.; TORRES, M. M.; PEREIRA, I. V. A.; JIMENEZ, D.; MUNTANELLI, B.; MALTA, F. M.; COGLIATI, B.; PINHO, J. R. R.; CARRILHO, F. J.; OLIVEIRA, C. P.- Association of a variant in the regulatory region of NADPH oxidase 4 gene and metabolic syndrome in patients with chronic hepatitis C(2015) SIQUEIRA, Erika Rabelo Forte de; PEREIRA, Luciano Beltrao; STEFANO, Jose Tadeu; PATENTE, Thiago; CAVALEIRO, Ana Mercedes; VASCONCELOS, Luydson Richardson Silva; CARMO, Rodrigo Feliciano; PEREIRA, Leila Maria Moreira Beltrao; CARRILHO, Flair Jose; CORREA-GIANNELLA, Maria Lucia; OLIVEIRA, Claudia P.Background: Given the important contribution of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system to the generation of reactive oxygen species induced by hepatitis C virus (HCV), we investigated two single nucleotide polymorphisms (SNPs) in the putative regulatory region of the genes encoding NADPH oxidase 4 catalytic subunit (NOX4) and its regulatory subunit p22phox (CYBA) and their relation with metabolic and histological variables in patients with HCV. Methods: One hundred seventy eight naive HCV patients (49.3% male; 65% HCV genotype 1) with positive HCV RNA were genotyped using specific primers and fluorescent-labeled probes for SNPs rs3017887 in NOX4 and -675 T -> A in CYBA. Results: No association was found between the genotype frequencies of NOX4 and CYBA SNPs and inflammation scores or fibrosis stages in the overall population. The presence of the CA + AA genotypes of the NOX4 SNP was nominally associated with a lower alanine aminotransferase (ALT) concentration in the male population (CA + AA = 72.23 +/- 6.34 U/L versus CC = 100.22 +/- 9.85; mean +/- SEM; P = 0.05). The TT genotype of the CYBA SNP was also nominally associated with a lower ALT concentration in the male population (TT = 84.01 +/- 6.77 U/L versus TA + AA = 109.67 +/- 18.37 U/L; mean +/- SEM; P = 0.047). The minor A-allele of the NOX4 SNP was inversely associated with the frequency of metabolic syndrome (MS) in the male population (odds ratio (OR): 0.15; 95% confidence interval (CI): 0.03 to 0.79; P = 0.025). Conclusions: The results suggest that the evaluated NOX4 and CYBA SNPs are not direct genetic determinants of fibrosis in HCV patients, but nevertheless NOX4 rs3017887 SNP could indirectly influence fibrosis susceptibility due to its inverse association with MS in male patients.
- Sorafenib prevents liver fibrosis in a non-alcoholic steatohepatitis (NASH) rodent model(2015) STEFANO, J. T.; PEREIRA, I. V. A.; TORRES, M. M.; BIDA, P. M.; COELHO, A. M. M.; XERFAN, M. P.; COGLIATI, B.; BARBEIRO, D. F.; MAZO, D. F. C.; KUBRUSLY, M. S.; D'ALBUQUERQUE, L. A. C.; SOUZA, H. P.; CARRILHO, F. J.; OLIVEIRA, C. P.Liver fibrosis occurring as an outcome of non-alcoholic steatohepatitis (NASH) can precede the development of cirrhosis. We investigated the effects of sorafenib in preventing liver fibrosis in a rodent model of NASH. Adult Sprague-Dawley rats were fed a choline-deficient high-fat diet and exposed to diethylnitrosamine for 6 weeks. The NASH group (n=10) received vehicle and the sorafenib group (n=10) received 2.5 mg.kg(-1).day(-1) by gavage. A control group (n=4) received only standard diet and vehicle. Following treatment, animals were sacrificed and liver tissue was collected for histologic examination, mRNA isolation, and analysis of mitochondrial function. Genes related to fibrosis (MMP9, TIMP1, TIMP2), oxidative stress (HSP60, HSP90, GST), and mitochondrial biogenesis (PGC1 alpha) were evaluated by real-time quantitative polymerase chain reaction (RT-qPCR). Liver mitochondrial oxidation activity was measured by a polarographic method, and cytokines by enzyme-linked immunosorbent assay (ELISA). Sorafenib treatment restored mitochondrial function and reduced collagen deposition by nearly 63% compared to the NASH group. Sorafenib upregulated PGC1 alpha and MMP9 and reduced TIMP1 and TIMP2 mRNA and IL-6 and IL-10 protein expression. There were no differences in HSP60, HSP90 and GST expression. Sorafenib modulated PGC1 alpha expression, improved mitochondrial respiration and prevented collagen deposition. It may, therefore, be useful in the treatment of liver fibrosis in NASH.
conferenceObject Molecular Characterization of the Fecal Microbiome in Brazilian Obese NASH patients compared to lean healthy controls.(2015) OLIVEIRA, Claudia P.; STEFANO, Jose Tadeu; RIBEIRO, Roberto M.; DUARTE, Sebastiao M.; RODRIGUES, Livia; CAMPOS, Priscila B.; COSTA, Fernando G.; MAZO, Daniel F.; CARRILHO, Flair J.; SABINO, Ester C.article 13 Citação(ões) na Scopus Physical training improves body weight and energy balance but does not protect against hepatic steatosis in obese mice(2015) EVANGELISTA, Fabiana S.; MULLER, Cynthia R.; STEFANO, Jose T.; TORRES, Mariana M.; MUNTANELLI, Bruna R.; SIMON, Daniel; ALVARES-DA-SILVA, Mario R.; PEREIRA, Isabel V.; COGLIATI, Bruno; CARRILHO, Flair J.; OLIVEIRA, Claudia P.This study sought to determine the role of physical training (PT) on body weight (BW), energy balance, histological markers of nonalcoholic fatty liver disease (NAFLD) and metabolic gene expression in the liver of ob/ob mice. Adult male ob/ob mice were assigned into groups sedentary (S; n = 8) and trained (T; n = 9). PT consisted in running sessions of 60 min at 60% of maximal speed conducted five days per week for eight weeks. BW of S group was higher from the 4th to 8th week of PT compared to their own BW at the beginning of the experiment. PT decreased daily food intake and increased resting oxygen consumption and energy expenditure in T group. No difference was observed in respiratory exchange ratio, but the rates of carbohydrate and lipids oxidation, and maximal running capacity were greater in T than S group. Both groups showed liver steatosis but not inflammation. PT increased CPT1a and SREBP1c mRNA expression in T group, but did not change MTP, PPAR-alpha, PPAR-gamma, and NFKB mRNA expression. In conclusion, PT prevented body weight gain in ob/ob mice by inducing negative energy balance and increased physical exercise tolerance. However, PT did not change inflammatory gene expression and failed to prevent liver steatosis possible due to an upregulation in the expression of SREBP1c transcription factor. These findings reveal that PT has positive effect on body weight control but not in the liver steatosis in a leptin deficiency condition.- Genetic ancestry analysis in non-alcoholic fatty liver disease patients from Brazil and Portugal(2015) CAVALCANTE, Lourianne Nascimento; STEFANO, Jose Tadeu; V, Mariana Machado; MAZO, Daniel F.; RABELO, Fabiola; SANDES, Kiyoko Abe; CARRILHO, Flair Jose; CORTEZ-PINTO, Helena; LYRA, Andre Castro; OLIVEIRA, Claudia P. deAIM: To study the association between genetic ancestry, non-alcoholic fatty liver disease (NAFLD) metabolic characteristics in two cohorts of patients, from Brazil and Portugal. METHODS: We included 131 subjects from Brazil [(n = 45 with simple steatosis (S. Steatosis) and n = 86 with nonalcoholic steatohepatitis (NASH)] and 90 patients from Portugal (n = 66, S. Steatosis; n = 24, NASH). All patients had biopsy-proven NAFLD. In histologic evaluation NAFLD activity score was used to assess histology and more than 5 points defined NASH in this study. Patients were divided into two groups according to histology diagnosis: simple steatosis or non-alcoholic statohepatitis. Genetic ancestry was assessed using real-time polymerase chain reaction. Seven ancestry informative markers (AT3-I/D, LPL, Sb19.3, APO, FY-Null, PV92, and CKMM) with the greatest ethnicgeographical differential frequencies (>= 48%) were used to define genetic ancestry. Data were analyzed using R PROJECTS software. Ancestry allele frequencies between groups were analyzed by GENEPOP online and the estimation of genetic ancestry contribution was evaluated by ADMIX-95 software. The 5% alpha-error was considered as significant (P < 0.05). RESULTS: In the Brazilian sample, NASH was significantly more frequent among the elderly patients with diabetes (NASH 56 +/- 1.1 years old vs S. Steatosis 51 +/- 1.5 years old, P = 3.7 x 10(-9)), dyslipidemia (NASH 63% vs S. Steatosis 37%, P = 0.009), higher fasting glucose levels (NASH 124 +/- 5.2 vs S. Steatosis 106 +/- 5.3, P = 0.001) and Homeostatic Model of Assessment index > 2.5 [NASH 5.3 (70.8%) vs S. Steatosis 4.6 (29.2%) P = 0.04]. In the Portuguese study population, dyslipidemia was present in all patients with NASH (P = 0.03) and hypertension was present in a larger percentage of subjects in the S. Steatosis group (P = 0.003, respectively). The genetic ancestry contribution among Brazilian and Portuguese individuals with NASH was similar to those with S. Steatosis from each cohort (Brazilian cohort: P = 0.75; Portuguese cohort: P = 0.97). Nonetheless, the genetic ancestry contribution of the Brazilian and Portuguese population were different, and a greater European and Amerindian ancestry contribution was detected in the Portuguese population while a higher African genetic ancestry contribution was observed in Brazilian population of both NASH and S. Steatosis groups. CONCLUSION: There was no difference between the genetic ancestry contribution among Brazilian and Portuguese individuals with NASH and S. Steatosis from each cohort.
- Genetic polymorphisms and oxidative stress in non-alcoholic steatohepatitis (NASH): A mini review(2015) OLIVEIRA, Claudia P.; STEFANO, Jose TadeuNon-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease, thus becoming an epidemic in the Western world with a major impact on public health. NAFLD encompasses a large spectrum of disease ranging from simple steatosis to non-alcoholic steatohepatitis (NASH) and may progress to fibrosis, cirrhosis and hepatocellular carcinoma (HCC). The role of genetic polymorphisms is not clear. Evidence supports the hypothesis that genetic factors are involved in the predisposition to NAFLD, and thus should emphasize the polygenic nature of the disease as a limiting factor in these studies. However, the polymorphic allele associated with increased hepatic steatosis appears to be associated with various different combinations of phenotypes, including increase or decrease of the biochemical and clinical parameters. It is possible that SNPs in genes involved in excessive fatty acid oxidation would predispose to NASH. On the other hand, the SNPs could determine the inadequate mitochondrial overload during times of excessive FFA supply. However due to the multiple hits involving some pathways, a brief review of genetic variants on mediators of oxidative stress, inflammation and lipid metabolism pathways is presented. It is clear that the discovery of genetic and environmental associations, robust enough to direct the treatment and to trace specific prevention strategies would only be possible with studies examining the susceptibility of NAFLD in a number of individuals considerably higher than assessed so far. These studies need a large number of well phenotyped cases and controls and certainly require national and international collaboration.
conferenceObject Omega-3 fatty acids improve proteomic and lipidomic markers of endoplasmic reticulum (ER) stress and mitochondrial dysfunction in a randomized controlled trial in subjects with Nonalcoholic Steatohepatitis(2015) RODRIGUES, Livia; OLIVEIRA, Claudia P.; STEFANO, Jose Tadeu; NOGUEIRA, Monize A.; SILVA, Ismael D.; TURCO, Edson G. Lo; ALVES, Venancio Avancini F.; CARRILHO, Flair J.; PURI, Puneet; WAITZBERG, DanconferenceObject IMPAIRED AEROBIC CAPACITY AND CARDIAC AUTONOMIC CONTROL IN SEDENTARY POSTMENOPAUSAL WOMEN WITH NONALCOHOLIC FATTY LIVER DISEASE (NAFLD)(2015) DUARTE, S. M.; REZENDE, R. E.; STEFANO, J. T.; PERANDINI, L. A.; DASSOUKI, T.; SA-PINTO, A. L.; ROSCHEL, H.; GUALANO, B.; CARRILHO, F. J.; OLIVEIRA, C. P.conferenceObject IMPACT OF AEROBIC EXERCISE IN POSTMENOPAUSAL WOMEN WITH NONALCOHOLIC FATTY LIVER DISEASE: A 24 WEEKS RANDOMIZED CLINICAL TRIAL(2015) REZENDE, R. E.; DUARTE, S. M.; STEFANO, J. T.; PERANDINI, L. A.; DASSOUKI, T.; SA-PINTO, A. L.; ROSCHEL, H.; GUALANO, B.; VEZOZZO, D. C.; CARRILHO, F. J.; OLIVEIRA, C. P.