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1.
PLoS One ; 15(9): e0232069, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32956351

RESUMO

Mouse models are frequently used to study mechanisms of human diseases. Recently, we observed a spontaneous bimodal variation in liver weight in C57BL/6JOlaHsd mice fed a semisynthetic diet. We now characterized the spontaneous variation in liver weight and its relationship with parameters of hepatic lipid and bile acid (BA) metabolism. In male C57BL/6JOlaHsd mice fed AIN-93G from birth to postnatal day (PN)70, we measured plasma BA, lipids, Very low-density lipoprotein (VLDL)-triglyceride (TG) secretion, and hepatic mRNA expression patterns. Mice were sacrificed at PN21, PN42, PN63 and PN70. Liver weight distribution was bimodal at PN70. Mice could be subdivided into two nonoverlapping groups based on liver weight: 0.6 SD 0.1 g (approximately one-third of mice, small liver; SL), and 1.0 SD 0.1 g (normal liver; NL; p<0.05). Liver histology showed a higher steatosis grade, inflammation score, more mitotic figures and more fibrosis in the SL versus the NL group. Plasma BA concentration was 14-fold higher in SL (p<0.001). VLDL-TG secretion rate was lower in SL mice, both absolutely (-66%, p<0.001) and upon correction for liver weight (-44%, p<0.001). Mice that would later have the SL-phenotype showed lower food efficiency ratios during PN21-28, suggesting the cause of the SL phenotype is present at weaning (PN21). Our data show that approximately one-third of C57BL/6JOlaHsd mice fed semisynthetic diet develop spontaneous liver disease with aberrant histology and parameters of hepatic lipid, bile acid and lipoprotein metabolism. Study designs involving this mouse strain on semisynthetic diets need to take the SL phenotype into account. Plasma lipids may serve as markers for the identification of the SL phenotype.


Assuntos
Ração Animal/efeitos adversos , Fígado Gorduroso/metabolismo , Fígado/patologia , Animais , Ácidos e Sais Biliares/sangue , Ácidos e Sais Biliares/metabolismo , Modelos Animais de Doenças , Ácidos Graxos/sangue , Ácidos Graxos/metabolismo , Fígado Gorduroso/sangue , Fígado Gorduroso/etiologia , Fígado Gorduroso/patologia , Feminino , Humanos , Metabolismo dos Lipídeos , Lipoproteínas VLDL/sangue , Lipoproteínas VLDL/metabolismo , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fatores Sexuais , Triglicerídeos/sangue , Triglicerídeos/metabolismo
2.
PLoS One ; 15(8): e0237840, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32822420

RESUMO

BACKGROUND AND OBJECTIVES: The hydroxylation to 25-hydroxy vitamin D (25(OH)D) occurs in the liver and the impact of liver disease on vitamin D is unclear. This study evaluated the relationship between vitamin D concentrations and hepatic histopathology, seasonality and patient characteristics in well-characterized patients having undergone a liver biopsy. METHOD: 25(OH)D was measured post-hoc in pre-treatment serum from 331 North European patients with chronic HCV genotype 2 or 3 infection (NORDynamIC study). Liver biopsies were scored for fibrosis and inflammation according to the Ishak protocol, and graded for steatosis. Non-invasive markers of hepatic fibrosis as well as baseline viral and host characteristics, including genetic polymorphisms rs2228570, rs7975232, and rs10877012 were also evaluated. RESULTS: Mean 25(OH)D concentration was 59 ±23 nmol/L, with 41% having values <50 nmol/L and 6% were <30 nmol/L. 25(OH)D correlated with fibrosis (r = -0.10, p ≤0.05) in univariate but not in multivariate analyses. No association was observed between 25(OH)D and hepatic inflammation, but with steatosis in HCV genotype 2 infected patients. None of the genetic polymorphisms impacted on 25(OH)D levels or fibrosis. 25(OH)D levels were significantly inversely correlated to BMI (r = -0.19, p = 0.001), and was also associated with season and non-Caucasian ethnicity. CONCLUSION: Fibrosis was not independently associated with 25(OH)D concentration and no association was seen with hepatic inflammation, but HCV genotype 2 infected patients with moderate-to-severe steatosis had lower 25(OH)D levels compared to those without steatosis. A high percentage had potential risk of 25(OH)D deficiency, and BMI, seasonality and ethnicity were independently associated with 25(OH)D as previously reported.


Assuntos
Fígado Gorduroso/sangue , Hepatite C Crônica/sangue , Cirrose Hepática/sangue , Fígado/patologia , Vitamina D/análogos & derivados , Adulto , Biópsia , Índice de Massa Corporal , Dinamarca , Grupos Étnicos , Europa (Continente)/epidemiologia , Fígado Gorduroso/genética , Fígado Gorduroso/patologia , Fígado Gorduroso/virologia , Feminino , Finlândia , Genótipo , Hepacivirus/genética , Hepacivirus/metabolismo , Hepatite C Crônica/genética , Hepatite C Crônica/patologia , Humanos , Fígado/citologia , Cirrose Hepática/genética , Cirrose Hepática/patologia , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Noruega , Polimorfismo Genético , Análise de Regressão , Estações do Ano , Suécia , Vitamina D/sangue
3.
BMJ Case Rep ; 13(8)2020 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-32784239

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has presented many diagnostic challenges and uncertainties. Little is known about common pathologies complicating pregnancy and how their behaviour is modified by the presence of SARS-CoV-2. Pregnancy itself can alter the body's response to viral infection, which can cause more severe symptoms. We report the first case of a patient affected with sudden-onset severe pre-eclampsia complicated by acute fatty liver disease of pregnancy, HELLP (haemolysis, elevated liver enzymes and low platelet) syndrome and acute kidney injury following SARS-CoV-2 infection. Although an initial diagnostic dilemma, a multidisciplinary team approach was required to ensure a favourable outcome for both the mother and the baby. Our case report highlights the need for health professionals caring for pregnant women to be aware of the complex interplay between SARS-CoV-2 infection and hypertensive disorders of pregnancy.


Assuntos
Lesão Renal Aguda/complicações , Betacoronavirus , Infecções por Coronavirus/complicações , Fígado Gorduroso/complicações , Síndrome HELLP/diagnóstico , Pneumonia Viral/complicações , Pré-Eclâmpsia/diagnóstico , Complicações Infecciosas na Gravidez/diagnóstico , Lesão Renal Aguda/sangue , Lesão Renal Aguda/diagnóstico , Adulto , Infecções por Coronavirus/sangue , Fígado Gorduroso/sangue , Fígado Gorduroso/diagnóstico , Feminino , Síndrome HELLP/sangue , Humanos , Testes de Função Renal , Pandemias , Pneumonia Viral/sangue , Pré-Eclâmpsia/sangue , Gravidez , Complicações na Gravidez/sangue , Complicações na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/sangue
4.
PLoS Genet ; 16(4): e1008629, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32282858

RESUMO

Analyzing 12,361 all-cause cirrhosis cases and 790,095 controls from eight cohorts, we identify a common missense variant in the Mitochondrial Amidoxime Reducing Component 1 gene (MARC1 p.A165T) that associates with protection from all-cause cirrhosis (OR 0.91, p = 2.3*10-11). This same variant also associates with lower levels of hepatic fat on computed tomographic imaging and lower odds of physician-diagnosed fatty liver as well as lower blood levels of alanine transaminase (-0.025 SD, 3.7*10-43), alkaline phosphatase (-0.025 SD, 1.2*10-37), total cholesterol (-0.030 SD, p = 1.9*10-36) and LDL cholesterol (-0.027 SD, p = 5.1*10-30) levels. We identified a series of additional MARC1 alleles (low-frequency missense p.M187K and rare protein-truncating p.R200Ter) that also associated with lower cholesterol levels, liver enzyme levels and reduced risk of cirrhosis (0 cirrhosis cases for 238 R200Ter carriers versus 17,046 cases of cirrhosis among 759,027 non-carriers, p = 0.04) suggesting that deficiency of the MARC1 enzyme may lower blood cholesterol levels and protect against cirrhosis.


Assuntos
Fígado Gorduroso/genética , Fígado Gorduroso/prevenção & controle , Predisposição Genética para Doença , Cirrose Hepática/genética , Cirrose Hepática/prevenção & controle , Proteínas Mitocondriais/genética , Mutação de Sentido Incorreto/genética , Oxirredutases/genética , Alelos , LDL-Colesterol/sangue , Doença da Artéria Coronariana/genética , Conjuntos de Dados como Assunto , Fígado Gorduroso/sangue , Fígado Gorduroso/enzimologia , Feminino , Homozigoto , Humanos , Fígado/enzimologia , Cirrose Hepática/sangue , Cirrose Hepática/enzimologia , Cirrose Hepática Alcoólica/sangue , Cirrose Hepática Alcoólica/enzimologia , Cirrose Hepática Alcoólica/genética , Cirrose Hepática Alcoólica/prevenção & controle , Mutação com Perda de Função/genética , Masculino , Pessoa de Meia-Idade
5.
Horm Metab Res ; 52(4): 236-245, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32110817

RESUMO

Apolipoprotein C3 is a lipid-binding protein with a pivotal role in triglyceride metabolism and inflammation. This 11-year follow-up study aimed to evaluate apolipoprotein C3 levels and other parameters as markers of hepatic steatosis, in a random, population-based cohort in southern Germany. In 2013, we selected and re-examined 406 study participants (193 women, 213 men; average age 58.1±11.3 years) from the original "Echinococcus multilocularis and other internal diseases in Leutkirch I" (EMIL I) cohort studied in 2002. All participants received upper abdominal sonography to grade potential hepatic steatosis, and blood tests to determine apolipoprotein C3 levels and other laboratory parameters. Body mass index, waist-to-hip ratio, and anthropometric measures were documented. The follow-up study conducted in 2013 included a partial correlation analysis. We found an association between hepatic steatosis and elevated apolipoprotein C3 levels (p<0.0001). Study participants with a novel diagnosis of hepatic steatosis had the highest apolipoprotein C3 serum levels (p=0.0002). Hepatic steatosis was associated with low levels of high density lipoprotein cholesterol (p=0.0374), high levels of total cholesterol (p=0.0117), increased homeostasis model assessment of insulin resistance (p=0.0002), elevated alanine transaminase (p<0.0001), elevated aspartate transaminase (p=0.0003), and elevated C-reactive protein (p=0.0446). Apolipoprotein C3 serum levels were associated with the presence, disease grade, and new development of hepatic steatosis likewise to biomarkers of the metabolic syndrome.


Assuntos
Apolipoproteína C-III/sangue , Fígado Gorduroso/sangue , Fígado Gorduroso/patologia , Abdome/diagnóstico por imagem , Adulto , Idoso , Biomarcadores/sangue , Estudos de Coortes , Estudos Transversais , Progressão da Doença , Fígado Gorduroso/diagnóstico por imagem , Fígado Gorduroso/epidemiologia , Feminino , Seguimentos , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Ultrassonografia
6.
Nutrients ; 12(2)2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32069846

RESUMO

Nutrient excess enhances glucose-dependent insulinotropic polypeptide (GIP) secretion, which may in turn contribute to the development of liver steatosis. We hypothesized that elevated GIP levels in obesity may affect markers of liver injury through microRNAs. The study involved 128 subjects (body mass index (BMI) 25-40). Fasting and postprandial GIP, glucose, insulin, and lipids, as well as fasting alanine aminotransferase (ALT), γ-glutamyltransferase (GGT), cytokeratin-18, fibroblast growth factor (FGF)-19, and FGF-21 were determined. TaqMan low density array was used for quantitative analysis of blood microRNAs. Fasting GIP was associated with ALT [ß = 0.16 (confidence interval (CI): 0.01-0.32)], triglycerides [ß = 0.21 (95% CI: 0.06-0.36], and FGF-21 [ß = 0.20 (95%CI: 0.03-0.37)]; and postprandial GIP with GGT [ß = 0.17 (95%CI: 0.03-0.32)]. The odds ratio for elevated fatty liver index (>73%) was 2.42 (95%CI: 1.02-5.72) for high GIP versus low GIP patients. The miRNAs profile related to a high GIP plasma level included upregulated miR-136-5p, miR-320a, miR-483-5p, miR-520d-5p, miR-520b, miR-30e-3p, and miR-571. Analysis of the interactions of these microRNAs with gene expression pathways suggests their potential contribution to the regulation of the activity of genes associated with insulin resistance, fatty acids metabolism, and adipocytokines signaling. Exaggerated fasting and postprandial secretion of GIP in obesity are associated with elevated liver damage markers as well as FGF-21 plasma levels. Differentially expressed microRNAs suggest additional, epigenetic factors contributing to the gut-liver cross-talk.


Assuntos
Fígado Gorduroso/sangue , Polipeptídeo Inibidor Gástrico/sangue , MicroRNAs/sangue , Obesidade/sangue , Adipocinas/sangue , Adulto , Idoso , Biomarcadores/sangue , Índice de Massa Corporal , Epigênese Genética , Jejum/sangue , Ácidos Graxos/sangue , Fígado Gorduroso/etiologia , Fígado Gorduroso/genética , Feminino , Fatores de Crescimento de Fibroblastos/sangue , Humanos , Insulina/sangue , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/genética , Razão de Chances , Período Pós-Prandial , Transdução de Sinais/genética
7.
Med Sci Monit ; 25: 9882-9886, 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31868169

RESUMO

BACKGROUND Platelets are considered to be essential in proinflammatory environments, including atherosclerosis. The degree of platelet activation has been demonstrated to be correlated with plateletcrit and platelet distribution width. The main purpose of this study was to assess the relationship between plateletcrit (PCT), platelet distribution, and the degree of hepatic steatosis in patients with non-alcoholic fatty liver disease (NAFLD). MATERIAL AND METHODS We enrolled 225 biopsy-proven NAFLD patients and 142 control subjects without NAFLD. NAFLD patients were separated into 2 groups according to percentage of steatosis. Demographic and clinical data were collected retrospectively. RESULTS PCT level was significantly higher in NAFLD group I and group II than in the control group. PCT was higher in the NAFLD groups than in the control group. However, there was no difference according to PCT and PDW levels between NAFLD groups. CONCLUSIONS In this study, a relationship was found between PCT and hepatosteatosis, but no relationship was found with PDW. PCT might be a useful biomarker for early detection of steatohepatitis in patients with nan-alcoholic fatty liver disease.


Assuntos
Plaquetas/metabolismo , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/metabolismo , Adulto , Biomarcadores , Estudos de Casos e Controles , Fígado Gorduroso/sangue , Fígado Gorduroso/metabolismo , Feminino , Humanos , Masculino , Volume Plaquetário Médio/métodos , Pessoa de Meia-Idade , Ativação Plaquetária/fisiologia , Contagem de Plaquetas/métodos , Curva ROC , Estudos Retrospectivos
8.
Nutrients ; 11(10)2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31591370

RESUMO

BACKGROUND: Hereditary fructose intolerance (HFI) is a rare genetic disorder of fructose metabolism due to aldolase B enzyme deficiency. Treatment consists of fructose, sorbitol, and sucrose (FSS)-free diet. We explore possible correlations between daily fructose traces intake and liver injury biomarkers on a long-term period, in a cohort of young patients affected by HFI. METHODS: Patients' clinical data and fructose daily intake were retrospectively collected. Correlations among fructose intake, serum alanine aminotransferase (ALT) level, carbohydrate-deficient transferrin (CDT) percentage, liver ultrasonography, genotype were analyzed. RESULTS: We included 48 patients whose mean follow-up was 10.3 ± 5.6 years and fructose intake 169 ± 145.4 mg/day. Eighteen patients had persistently high ALT level, nine had abnormal CDT profile, 45 had signs of liver steatosis. Fructose intake did not correlate with ALT level nor with steatosis severity, whereas it correlated with disialotransferrin percentage (R2 0.7, p < 0.0001) and tetrasialotransferrin/disialotransferrin ratio (R2 0.5, p = 0.0001). p.A150P homozygous patients had lower ALT values at diagnosis than p.A175D variant homozygotes cases (58 ± 55 IU/L vs. 143 ± 90 IU/L, p = 0.01). CONCLUSION: A group of HFI patients on FSS-free diet presented persistent mild hypertransaminasemia which did not correlate with fructose intake. Genotypes may influence serum liver enzyme levels. CDT profile represents a good marker to assess FSS intake.


Assuntos
Dieta com Restrição de Carboidratos , Fígado Gorduroso/etiologia , Intolerância à Frutose/dietoterapia , Frutose/efeitos adversos , Adolescente , Alanina Transaminase/sangue , Biomarcadores/sangue , Criança , Fígado Gorduroso/sangue , Fígado Gorduroso/diagnóstico por imagem , Feminino , Frutose/metabolismo , Intolerância à Frutose/complicações , Intolerância à Frutose/diagnóstico , Intolerância à Frutose/genética , Frutose-Bifosfato Aldolase/genética , Predisposição Genética para Doença , Humanos , Masculino , Mutação , Fenótipo , Estudos Retrospectivos , Índice de Gravidade de Doença , Sialoglicoproteínas/sangue , Transferrina/análogos & derivados , Transferrina/metabolismo
9.
Medicine (Baltimore) ; 98(39): e17300, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574855

RESUMO

We investigated associations between inflammatory marker levels and hepatitis C virus (HCV)-related compensated liver cirrhosis risk in patients with chronic hepatitis C (CHC) infection in China. We used a case-control design and data from the records of 110 Chinese patients with CHC and cirrhosis for the study; 458 CHC patients who did not have a diagnosis of cirrhosis were matched to the case group by age and sex characteristics. We also investigated fatty liver disease risk factors. The group of patients with CHC infection and cirrhosis had lower platelet-to-lymphocyte ratio (PLR) values (60.63 [44.09, 89.31]) compared with the control group patients (80.24 [57.85, 111.08]). The results indicated that the group of patients with cirrhosis had higher 4-factor fibrosis index and aspartate aminotransferase (AST)-to-platelet ratio index (APRI) values compared with the group of patients with CHC-only (1.66 [0.98, 2.60] vs 0.71 [0.45, 1.17], respectively; P < .001 and 2.12 [0.97, 4.25] vs 0.99 [0.51, 2.01], respectively; P < .001). Compared with the control group, the AST/alanine aminotransferase ratio (AAR) values in the group of patients with cirrhosis were significantly higher (P < .001). Logistic regression analysis that included model adjustment for demographic characteristics and other factors that could affect cirrhosis risk revealed that greater 1/PLR values were associated with an increased odds of having cirrhosis (adjusted odds ratio [AOR], 95% confidence interval [CI] 0.991 [0.985-0.996]); APRI and AAR values were also independent predictors of the presence of compensated cirrhosis. We found that compared with the patients with CHC-only, the triglyceride, cholesterol, and low-density lipoprotein cholesterol levels in the patients with both CHC and fatty liver disease were significantly higher. The multivariate analysis of the risk of fatty liver development in patients with CHC infection found that cholesterol level was a statistically significant risk factor (AOR [95% CI] 1.380 [1.089-1.750], P = .008). Increased 1/PLR, APRI, and AAR values were associated with increased risks for development of cirrhosis in this population of Chinese patients with CHC infection. Higher cholesterol levels increased the risk of development of fatty liver disease in patients with CHC.


Assuntos
Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Hepatite C Crônica , Cirrose Hepática , Biomarcadores/sangue , Estudos de Casos e Controles , China/epidemiologia , Fígado Gorduroso/sangue , Fígado Gorduroso/diagnóstico , Fígado Gorduroso/epidemiologia , Feminino , Hepacivirus/isolamento & purificação , Hepatite C Crônica/sangue , Hepatite C Crônica/complicações , Hepatite C Crônica/epidemiologia , Humanos , Lipoproteínas/sangue , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , Cirrose Hepática/etiologia , Contagem de Linfócitos/métodos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas/métodos , Fatores de Risco
10.
Am J Physiol Regul Integr Comp Physiol ; 317(5): R733-R745, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31483154

RESUMO

Agonists for PPARα are used clinically to reduce triglycerides and improve high-density lipoprotein (HDL) cholesterol levels in patients with hyperlipidemia. Whether the mechanism of PPARα activation to lower serum lipids occurs in the liver or other tissues is unknown. To determine the function of hepatic PPARα on lipid profiles in diet-induced obese mice, we placed hepatocyte-specific peroxisome proliferator-activated receptor-α (PPARα) knockout (PparaHepKO) and wild-type (Pparafl/fl) mice on high-fat diet (HFD) or normal fat diet (NFD) for 12 wk. There was no significant difference in weight gain, percent body fat mass, or percent body lean mass between the groups of mice in response to HFD or NFD. Interestingly, the PparaHepKO mice on HFD had worsened hepatic inflammation and a significant shift in the proinflammatory M1 macrophage population. These changes were associated with higher hepatic fat mass and decreased hepatic lean mass in the PparαHepKO on HFD but not in NFD as measured by Oil Red O and noninvasive EchoMRI analysis (31.1 ± 2.8 vs. 20.2 ± 1.5, 66.6 ± 2.5 vs. 76.4 ± 1.5%, P < 0.05). We did find that this was related to significantly reduced peroxisomal gene function and lower plasma ß-hydroxybutyrate in the PparaHepKO on HFD, indicative of reduced metabolism of fats in the liver. Together, these provoked higher plasma triglyceride and apolipoprotein B100 levels in the PparaHepKO mice compared with Pparafl/fl on HFD. These data indicate that hepatic PPARα functions to control inflammation and liver triglyceride accumulation that prevent hyperlipidemia.


Assuntos
Fígado Gorduroso/metabolismo , Hepatócitos/metabolismo , Hiperlipidemias/metabolismo , Inflamação/metabolismo , Metabolismo dos Lipídeos , Fígado/metabolismo , Obesidade/metabolismo , PPAR alfa/deficiência , Adiposidade , Animais , Apolipoproteína B-100/sangue , Citocinas/metabolismo , Dieta Hiperlipídica , Modelos Animais de Doenças , Fígado Gorduroso/sangue , Fígado Gorduroso/genética , Fígado Gorduroso/patologia , Hepatócitos/patologia , Hiperlipidemias/sangue , Hiperlipidemias/genética , Hiperlipidemias/patologia , Inflamação/sangue , Inflamação/genética , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Fígado/patologia , Camundongos Knockout , Obesidade/sangue , Obesidade/genética , Obesidade/patologia , PPAR alfa/genética , Triglicerídeos/sangue
11.
Lipids Health Dis ; 18(1): 170, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31511022

RESUMO

BACKGROUND: Atherogenic index of plasma (AIP) has been reported to be an important predictor for coronary artery disease and obesity. However, few studies has yet systematically evaluated the association between AIP and Fatty Liver (FL) and its advantage in FL prediction compared with BMI, waist, SBP, DBP, BG, ALT and AST. METHODS: A total of 7838 participants aged from 19 to 93 years were included in this study. Height, weight, waist, SBP, DBP, BG, ALT and AST were measured. Difference analyses, odds ratio calculation, logistic and predictive analyses were used to evaluate the association and discrimination ability between AIP, BMI, waist, SBP, DBP, BG, ALT, AST and FL. RESULTS: Compared with non-FL, AIP in FL people showed a significant increase. Subjects in the higher quartiles of AIP had a significantly increased risk of fatty liver compared with those in the lowest quartile (P < 0.01) after adjustment of gender and age. ORs were grown faster in female and youth group. AIP contributed most in the logistic eq. (B = 2.64, P < 0.01) and showed high ability in risk prediction for FL (AUC = 0.810, P < 0.01). CONCLUSIONS: AIP might be a novel and strong predictor associated with FL in Chinese Han population. Higher AIP level was positively and strongly associated with FL.


Assuntos
Aterosclerose/diagnóstico , HDL-Colesterol/sangue , Fígado Gorduroso/diagnóstico , Triglicerídeos/sangue , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/sangue , Grupo com Ancestrais do Continente Asiático , Aspartato Aminotransferases/sangue , Aterosclerose/sangue , Aterosclerose/etnologia , Aterosclerose/patologia , Biomarcadores/sangue , Glicemia/metabolismo , Pressão Sanguínea , Índice de Massa Corporal , Estudos Transversais , Diástole , Fígado Gorduroso/sangue , Fígado Gorduroso/etnologia , Fígado Gorduroso/patologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prognóstico , Fatores Sexuais , Sístole , Circunferência da Cintura
12.
Endocr J ; 66(11): 995-1000, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31292303

RESUMO

We investigated the factors associated with fatty liver remission via treatment with ipragliflozin. The analysis was obtained from our multi-center prospective observational study, including 200 Japanese patients with type 2 diabetes treated with ipragliflozin (50 mg/day) for 24 weeks. The extent of fatty liver was estimated using a fatty liver index (FLI). Based on the FLI after the treatment with ipragliflozin, patients were classified into remission group (FLI < 30) and non-remission group (FLI ≥ 30). After treatment with ipragliflozin for 24 weeks, FLI significantly improved from 64.5 ± 21.6 to 51.9 ± 26.5 (p < 0.01). Body weight, body mass index, waist circumference, aspartate aminotransferase, alanine aminotransferase, and FLI in the remission group were significantly lower compared with those of the non-remission group. Stepwise analysis showed that the baseline FLI (Odds ratio 0.86; 95% confidence interval 0.81-0.90, p < 0.01) was an independent factor associated with FLI remission. Using a receiver operating characteristic (ROC) analysis, the adequate cut-off value for the remission was 50. The area under the ROC curve was 0.93 with the sensitivity and specificity 84.6% and 90.1% respectively. In conclusion, ipragliflozin ameliorated fatty liver. These results suggest that patients with fatty liver with a lower FLI are more likely to attain remission by the treatment with ipragliflozin.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Fígado Gorduroso/sangue , Glucosídeos/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Tiofenos/uso terapêutico , Idoso , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/complicações , Fígado Gorduroso/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Resultado do Tratamento , Triglicerídeos/sangue , Circunferência da Cintura , gama-Glutamiltransferase/sangue
13.
PLoS One ; 14(7): e0219526, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31295293

RESUMO

BACKGROUND AND AIMS: Although combined antiretroviral treatment (cART) has improved overall survival of HIV infected patients, liver fibrosis and liver related-mortality still constitute major challenges in HIV positive patients. Collagen accumulates in the liver during fibrogenesis. Recent studies showed that circulating levels of extracellular matrix (ECM) fragments might reflect degree of portal hypertension and fibrosis stage in liver disease. In this study, we analyzed the correlation between liver fibrosis assessed by Fibroscan and levels of the formation and degradation markers of type III and IV collagen in HIV positive patients receiving cART. METHODS: 116 HIV positive patients (82.7% male, median age 47 years) were enrolled into the study. Liver stiffness and liver fat content were determined using a Fibroscan with integrated CAP function. We quantified ECM formation and degradation fragments of collagen III and IV: PRO-C3, PRO-C4, C3M and C4M. These fragments were measured in peripheral serum by using specific ELISAs. RESULTS: Fifteen (12.9%) out of the 116 HIV positive patients had relevant fibrosis with a liver stiffness ≥ 7.1 kPa, and 79 patients had relevant steatosis with a CAP value > 248 dB/m. Circulating PRO-C3 levels significantly correlated with increasing degree of liver fibrosis assessed by Fibroscan (p = 0.0005), as well as with APRI score (p = 0.015). Interestingly, circulating PRO-C3 levels were significantly correlated with bilirubin (p = 0.022), reduced platelet count (p = 0.0008) and low albumin levels (p = 0.001), suggesting the association of type III collagen deposition with impaired liver function. None of the other measured ECM components significantly correlated with fibrosis or steatosis. CONCLUSION: The formation marker of type III collagen, PRO-C3 not only reflects liver fibrosis, but might also mirror liver dysfunction in HIV positive patients receiving cART. Therefore, the circulating levels of PRO-C3 might be suitable to monitor progression of liver fibrosis and deterioration of liver function in HIV positive patients receiving cART.


Assuntos
Complemento C3/metabolismo , Complemento C4/metabolismo , Fígado Gorduroso/sangue , Infecções por HIV/sangue , Cirrose Hepática/sangue , Adulto , Antirretrovirais/administração & dosagem , Terapia Antirretroviral de Alta Atividade , Biomarcadores/sangue , Colágeno Tipo III/sangue , Colágeno Tipo IV/sangue , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Matriz Extracelular/genética , Fígado Gorduroso/patologia , Fígado Gorduroso/virologia , Feminino , HIV/genética , HIV/patogenicidade , Infecções por HIV/tratamento farmacológico , Infecções por HIV/patologia , Infecções por HIV/virologia , Humanos , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/patologia , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade
14.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1864(10): 1293-1304, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31170503

RESUMO

BACKGROUND: Bile acids (BAs) participate in lipid absorption and serve as metabolic regulatory factors in gut-liver communication. To date, there are no studies on the systemic patterns of BAs in the serum, liver, and gut in the same non-alcoholic fatty liver disease (NAFLD) model. METHODS: A targeted metabolomics approach and 16S rRNA sequencing were used to identify the profile of BAs and connection between BAs and microbiota. The role and mechanism of altered BAs on hepatic steatosis were investigated. FINDINGS: In the liver, the composition of taurocholic acid (TCA) was increased, but taurohyodeoxycholic acid (THDCA) and ursodeoxycholic acid (UDCA) were decreased. In the gut, the deconjugated form of TCA (cholic acid (CA)) was increased, while the deconjugated forms of THDCA (α-hyodeoxycholic acid (HDCA)) and ω-muricholic acid (ωMCA) were decreased. In the serum, the composition of TCA was increased, while both HDCA and THDCA were decreased. THDCA induced the gene expression of apolipoprotein, bile secretion-related proteins, and cytochrome P450 family but suppressed inflammatory response genes expression in steatotic hepatocytes by RNAseq analysis. THDCA ameliorated neutral lipid accumulation and improved insulin sensitivity in primary rat hepatocytes. The decreased HDCA level correlated with the level of Bacteroidetes, while the level of CA correlated with the levels of Firmicutes and Verrucomicrobia but correlated inversely with Bacteroidetes. CONCLUSION: BAs profiles in the serum, liver and caecal content were altered in a rat NAFLD model, which may affect hepatic lipid accumulation and correlate with gut dysbiosis.


Assuntos
Ácidos e Sais Biliares/metabolismo , Ceco/metabolismo , Fígado Gorduroso/metabolismo , Fígado/metabolismo , Animais , Ácidos e Sais Biliares/sangue , Células Cultivadas , Dieta Hiperlipídica , Fígado Gorduroso/sangue , Microbioma Gastrointestinal , Masculino , Ratos Sprague-Dawley
15.
Medicina (Kaunas) ; 55(6)2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31163711

RESUMO

Background and objectives: Data suggests that nearly 30% of the general population have steatosis and up to 5% of this population develops nonalcoholic steatohepatitis (NASH). Liver biopsy is still considered to be the gold standard for the diagnosis of NASH. Great effort is being made toward the identification of sensitive diagnostic tests that do not involve invasive procedures to address a common concern in patients with the nonalcoholic fatty liver disease-whether they have NASH or simple steatosis. We aimed to investigate the independent predictors and develop a non-invasive, easy-to-perform, low-cost set of parameters that may be used in clinical practice to differentiate simple steatosis from NASH. Methods: А cross-sectional study of nonalcoholic fatty liver disease (NAFLD) patients divided into two groups: group I-simple steatosis (SS) and group II-biopsy-proven NASH. Strict inclusion criteria and stepwise analysis allowed the evaluation of a vast number of measured/estimated parameters. Results: One hundred and eleven patients were included-82 with simple steatosis and 29 with biopsy-proven NASH. The probability of NASH was the highest when homeostatic model assessment of insulin resistance (HOMA-IR) was above 2.5, uric acid above 380 µmol/L, ferritin above 100 µg/L and ALT above 45 U/L. An acronym of using first letters was created and named the HUFA index. This combined model resulted in an area under the receiver operator characteristic curve (AUROC) of 0.94, provided sensitivity, specificity, positive predictive value and a negative predictive value for NASH of 70.3%, 95.1%, 83.1% and 90.0%, respectively. Conclusion: We suggest a simple non-invasive predictive index HUFA that encompasses four easily available parameters (HOMA-IR, uric acid, ferritin and ALT) to identify patients with NASH, which may reduce the need for a liver biopsy on a routine basis in patients with NAFLD.


Assuntos
Fígado Gorduroso/sangue , Hepatopatia Gordurosa não Alcoólica/sangue , Adulto , Idoso , Análise de Variância , Biomarcadores/análise , Biomarcadores/sangue , Distribuição de Qui-Quadrado , Estudos Transversais , Fígado Gorduroso/diagnóstico , Fígado Gorduroso/fisiopatologia , Feminino , Ferritinas/análise , Ferritinas/sangue , Humanos , Resistência à Insulina/fisiologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Curva ROC , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Ácido Úrico/análise , Ácido Úrico/sangue
16.
Transl Res ; 210: 26-42, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31121128

RESUMO

Obesity is a major cause of metabolic syndrome and type II diabetes, and it presents with metabolic disorders, such as hyperglycemia, hyperlipidemia, and insulin resistance. Pigment epithelium-derived factor (PEDF), a protein isolated from retinal pigment epithelial cells, has multiple functions, including neuronal protection, antineoplastic effects, and anti-inflammatory activity. The aim of this study is to investigate the antiobesity effects of PEDF. The antiobesity effects of PEDF on fat accumulation, inflammation, energy expenditure, insulin resistance, and obesity-related physiological parameters and protein levels were assessed in high-fat diet (HFD)-induced obese mice in vivo and in 3T3-L1 adipocytes, palmitate (PA)-treated HepG2 cells, and C2C12 myotubes in vitro. In an in vivo assay, PEDF effectively decreased body weight gain, white adipose tissue mass, and inflammation and improved insulin resistance, dyslipidemia, and hyperglycemia in HFD-induced mice. In liver tissue, PEDF decreased lipid accumulation and fibrosis. In an in vitro assay, PEDF diminished the differentiation of 3T3-L1 preadipocytes. We also determined that PEDF promoted lipolysis and prolonged cell cycle progression, through the mTOR-S6K pathway and downstream transcription factors, such as peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein α (CEBP-α), and CEBP-ß. In addition, PEDF decreased reactive oxygen species production in PA-induced HepG2 cells and improved glucose uptake ability in PA-induced HepG2 cells and C2C12 myotubes. In the present study, PEDF protected against HFD-induced obesity and metabolic disorders in mice, inhibited adipogenesis, and improved insulin resistance. These results provide a new potential treatment for obesity in the future.


Assuntos
Adipócitos/metabolismo , Adipogenia/efeitos dos fármacos , Proteínas do Olho/farmacologia , Doenças Metabólicas/patologia , Fatores de Crescimento Neural/farmacologia , Obesidade/patologia , Obesidade/prevenção & controle , Serpinas/farmacologia , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Tecido Adiposo/patologia , Animais , Proliferação de Células/efeitos dos fármacos , Células Clonais , Dieta Hiperlipídica , Fígado Gorduroso/sangue , Fígado Gorduroso/complicações , Fígado Gorduroso/patologia , Células Hep G2 , Humanos , Inflamação/patologia , Resistência à Insulina , Masculino , Doenças Metabólicas/sangue , Camundongos , Camundongos Endogâmicos C57BL , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Obesidade/sangue , Obesidade/complicações , Estresse Oxidativo/efeitos dos fármacos , Ácido Palmítico , Proteínas Quinases S6 Ribossômicas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo
17.
Gastroenterology ; 157(3): 705-719.e18, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31121167

RESUMO

BACKGROUND & AIMS: Alpha-1 antitrypsin deficiency (AATD) is among the most common genetic disorders. Severe AATD is caused by a homozygous mutation in the SERPINA1 gene that encodes the Glu342Lys substitution (called the Pi*Z mutation, Pi*ZZ genotype). Pi*ZZ carriers may develop lung and liver diseases. Mutation-associated lung disorders have been well studied, but less is known about the effects in liver. We assessed the liver disease burden and associated features in adults with this form of AATD. METHODS: We collected data from 554 Pi*ZZ adults (403 in an exploratory cohort, 151 in a confirmatory cohort), in 9 European countries, with AATD who were homozygous for the Pi*Z mutation, and 234 adults without the Pi*Z mutation (controls), all without pre-existing liver disease. We collected data on demographic parameters, comorbidities, lung- and liver-related health, and blood samples for laboratory analysis. Liver fibrosis was assessed non-invasively via the serum tests Aspartate Aminotransferase to Platelet Ratio Index and HepaScore and via transient elastography. Liver steatosis was determined via transient elastography-based controlled attenuation parameter. We performed histologic analyses of livers from transgenic mice that overexpress the AATD-associated Pi*Z variant. RESULTS: Serum levels of liver enzymes were significantly higher in Pi*ZZ carriers vs controls. Based on non-invasive tests for liver fibrosis, significant fibrosis was suspected in 20%-36% of Pi*ZZ carriers, whereas signs of advanced fibrosis were 9- to 20-fold more common in Pi*ZZ carriers compared to non-carriers. Male sex; age older than 50 years; increased levels of alanine aminotransferase, aspartate aminotransferase, or γ-glutamyl transferase; and low numbers of platelets were associated with higher liver fibrosis burden. We did not find evidence for a relationship between lung function and liver fibrosis. Controlled attenuation parameter ≥280 dB/m, suggesting severe steatosis, was detected in 39% of Pi*ZZ carriers vs 31% of controls. Carriers of Pi*ZZ had lower serum concentrations of triglyceride and low- and very-low-density lipoprotein cholesterol than controls, suggesting impaired hepatic secretion of lipid. Livers from Pi*Z-overexpressing mice had steatosis and down-regulation of genes involved in lipid secretion. CONCLUSIONS: In studies of AATD adults with the Pi*ZZ mutation, and of Pi*Z-overexpressing mice, we found evidence of liver steatosis and impaired lipid secretion. We identified factors associated with significant liver fibrosis in patients, which could facilitate hepatologic assessment and counseling of individuals who carry the Pi*ZZ mutation. ClinicalTrials.gov Number NCT02929940.


Assuntos
Fígado Gorduroso/etiologia , Metabolismo dos Lipídeos , Cirrose Hepática/etiologia , Fígado/metabolismo , Mutação , Deficiência de alfa 1-Antitripsina/complicações , alfa 1-Antitripsina/genética , Adulto , Fatores Etários , Idoso , Animais , Estudos de Casos e Controles , Técnicas de Imagem por Elasticidade , Europa (Continente) , Fígado Gorduroso/sangue , Fígado Gorduroso/diagnóstico , Feminino , Predisposição Genética para Doença , Homozigoto , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico , Testes de Função Hepática , Masculino , Camundongos Transgênicos , Pessoa de Meia-Idade , Fenótipo , Fatores de Risco , Fatores Sexuais , Deficiência de alfa 1-Antitripsina/diagnóstico , Deficiência de alfa 1-Antitripsina/enzimologia , Deficiência de alfa 1-Antitripsina/genética
18.
Biomed Pharmacother ; 116: 108959, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31108350

RESUMO

AIMS: To investigate the role of pancreastatin inhibitor (PSTi8) in lipid homeostasis and insulin sensitivity in dexamethasone induced fatty liver disease associated type 2 diabetes. MAIN METHODS: Glucose releases assay, lipid O staining and ATP/AMP ratio were performed in HepG2 cells. Twenty four mice were randomly divided into 4 groups: Control group (saline), DEX (1 mg/kg, im) for 17 days, DEX+PSTi8 (acute 5 mg/kg and chronic 2 mg/kg, ip) for 10 days. The glucose, insulin and pyruvate tolerance tests (GTT, ITT and PTT), biochemical parameters and Oxymax-CLAMS were performed. Further to elucidate the action mechanisms of PSTi8, we performed genes expression and western blotting of biological samples. KEY FINDINGS: We found that PSTi8 suppresses hepatic glucose release, lipid deposition, oxidative stress induced by DEX, stimulates the cellular energy level in hepatocytes and enhances GRP78 activity. It reduces lipogensis and enhances fatty acid oxidation to improve insulin sensitivity and glucose tolerance in DEX induced diabetic mice. The above cellular effects are the result of activated AMPK signalling pathway in liver, which increases Srebp1c and ACC phosphorylation. The increased ACC phosphorylation suppresses protein kinase C activity and enhances insulin sensitivity. The increased expression of UCP3 in liver elicits fatty acid oxidation and energy expenditure, which suppress oxidative stress. SIGNIFICANCE: Thus the activation of AMPK signalling through GRP78, improves lipid homeostasis, enhances insulin sensitivity via inhibition of PKC activity. PSTi8 suppresses inflammation associated with incomplete fatty acid oxidation. Hence, PSTi8 may be a potential therapeutic agent to treat glucocorticoid-induced fatty liver associated type 2 diabetes.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Cromogranina A/antagonistas & inibidores , Fígado Gorduroso/enzimologia , Fígado Gorduroso/patologia , Proteínas de Choque Térmico/metabolismo , Transdução de Sinais , Trifosfato de Adenosina/metabolismo , Adipocinas/metabolismo , Adiposidade/efeitos dos fármacos , Animais , Cromogranina A/metabolismo , Dexametasona , Metabolismo Energético , Fígado Gorduroso/sangue , Glucose/metabolismo , Células Hep G2 , Homeostase/efeitos dos fármacos , Humanos , Insulina/sangue , Resistência à Insulina , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos Endogâmicos C57BL , Distribuição Tecidual/efeitos dos fármacos
19.
Int J Mol Sci ; 20(9)2019 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-31075962

RESUMO

This study focuses on the effect of honokiol (HON) on glucose homeostasis, insulin resistance, dyslipidemia, hepatic steatosis, and inflammation in type 2 diabetic db/db mice. Male C57BL/KsJ-db/db mice were fed a normal diet with or without HON (0.02%, w/w) or pioglitazone (PIO, anti-diabetic agent, 0.01%, w/w) for 5 weeks. Blood biomarker, tissue morphology and enzymatic and genetic parameters were determined. PIO significantly decreased food intake, fasting blood glucose, and glycosylated hemoglobin (HbA1c) levels, but markedly increased body weight, adipose tissue weight, and plasma leptin levels. HON did not significantly affect food intake, body weight, or levels of plasma leptin and blood glucose. However, HON led to significant decreases in adipose tissue weight, plasma insulin, blood HbA1c and HOMA-IR levels and improved glucose tolerance. The anti-diabetic and anti-adiposity effects of HON were partially related to the inhibition of gluconeogenic enzymes and their mRNA expression in the liver; and the inhibition of lipogenic enzymes in adipose tissue, respectively. Unlike PIO, HON did not affect dyslipidemia, but ameliorated hepatic steatosis by inhibiting hepatic lipogenic enzymes activity. Moreover, HON exhibited anti-inflammatory effects similar to PIO. These results suggest that HON can protect against type 2 diabetes by improving insulin resistance, glucose and lipid metabolism, and inflammation.


Assuntos
Compostos de Bifenilo/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Fígado Gorduroso/tratamento farmacológico , Inflamação/tratamento farmacológico , Resistência à Insulina , Lignanas/uso terapêutico , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/patologia , Animais , Compostos de Bifenilo/farmacologia , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Citocinas/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/patologia , Dislipidemias/sangue , Dislipidemias/complicações , Fígado Gorduroso/sangue , Fígado Gorduroso/complicações , Fígado Gorduroso/patologia , Comportamento Alimentar/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Inflamação/sangue , Inflamação/complicações , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Leptina/sangue , Lignanas/farmacologia , Lipídeos/sangue , Masculino , Camundongos Endogâmicos C57BL , Tamanho do Órgão/efeitos dos fármacos
20.
Molecules ; 24(7)2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30987086

RESUMO

Mixtures of resveratrol (RSV) + quercetin (QRC) have antioxidant properties that probably impact on fatty liver in metabolic syndrome (MS) individuals. Here, we study the effects of a mixture of RSV + QRC on oxidative stress (OS) and fatty liver in a rat model of MS. Weanling male Wistar rats were separated into four groups (n = 8): MS rats with 30% sucrose in drinking water plus RSV + QRC (50 and 0.95 mg/kg/day, respectively), MS rats without treatment, control rats (C), and C rats plus RSV + QRC. MS rats had increased systolic blood pressure, triglycerides, insulin levels, insulin resistance index homeostasis model (HOMA), adiponectin, and leptin. The RSV + QRC mixture compensated these variables to C values (p < 0.01) in MS rats. Lipid peroxidation and carbonylation were increased in MS. Total antioxidant capacity and glutathione (GSH) were decreased in MS and compensated in MS plus RVS + QRC rats. Catalase, superoxide dismutase isoforms, peroxidases, glutathione-S-transferase, glutathione reductase, and the expression of Nrf2 were decreased in MS and reversed in MS plus RVS + QRC rats (p < 0.01). In conclusion, the mixture of RSV + QRC has benefic effects on OS in fatty liver in the MS rats through the improvement of the antioxidant capacity and by the over-expression of the master factor Nrf2, which increases the antioxidant enzymes and GSH recycling.


Assuntos
Antioxidantes/metabolismo , Fígado Gorduroso/etiologia , Fígado Gorduroso/metabolismo , Síndrome Metabólica/complicações , Síndrome Metabólica/metabolismo , Quercetina/administração & dosagem , Resveratrol/administração & dosagem , Animais , Biomarcadores , Modelos Animais de Doenças , Fígado Gorduroso/sangue , Fígado Gorduroso/prevenção & controle , Glutationa/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Síndrome Metabólica/sangue , Estresse Oxidativo/efeitos dos fármacos , Ratos
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