The effect of taurine on hepatic steatosis induced by thioacetamide in zebrafish (Danio rerio).

BACKGROUND: Nonalcoholic fatty liver disease is one of the most prevalent forms of chronic liver disease in the Western world. Taurine is a conditionally essential amino acid in humans that may be a promising therapy for treating this disease. AIM: To evaluate the effect of taurine on hepatic steatosis induced by thioacetamide in Danio rerio. METHODS: Animals were divided into four groups: control (20 µl of saline solution), taurine (1,000 mg/kg), thioacetamide (300 mg/kg), and the taurine-thioacetamide group (1,000 + 300 mg/kg). Thioacetamide was injected intraperitoneally three times a week for 2 weeks. The mRNA expression, lipoperoxidation, antioxidant enzymatic activity, and histological analyses were evaluated in the liver and the triglyceride content was assessed in the serum. RESULTS: Thioacetamide injection induced steatosis, as indicated by histological analyses. The lipoperoxidation showed significant lipid damage in the thioacetamide group compared to the taurine-thioacetamide group (p < 0.001). Superoxide dismutase (SOD) activity in the taurine-thioacetamide group (5.95 ± 0.40) was significantly increased compared to the thioacetamide group (4.14 ± 0.18 U SOD/mg of protein) (p < 0.001). The mRNA expression of SIRT1 (0.5-fold) and Adiponectin receptor 2 (0.39-fold) were lower in the thioacetamide group than the control (p < 0.05). TNF-α mRNA expression was 6.4-fold higher in the thioacetamide group than the control (p < 0.05). SIRT1 mRNA expression was 2.6-fold higher in the taurine-thioacetamide group than in the thioacetamide group. CONCLUSIONS: Taurine seems to improve hepatic steatosis by reducing oxidative stress and increasing SIRT1 expression.

Phase Angle Is an Independent Predictor of 6-Month Mortality in Patients With Decompensated Cirrhosis: A Prospective Cohort Study.

BACKGROUND: This study aimed to evaluate the nutrition status through phase angle (PA) and its association with mortality in patients with decompensated cirrhosis. METHODS: A prospective cohort study was performed with hospitalized decompensated cirrhotic patients. Nutrition status was assessed by PA, bioelectrical impedance vector analysis (BIVA), and Subjective Global Assessment (SGA) within 72 hours of hospital admission. The best PA cutoff point for malnutrition diagnosis was determined by ROC curve analysis, considering the SGA as the reference standard. Predictors of 6-month mortality were identified using Cox proportional hazards models, adjusted for Child-Pugh and MELD scores, and hepatocellular carcinoma. RESULTS: This study included 97 patients, 63% male (n = 61), with a mean age of 60.1 ± 10.3 years. The median follow-up time of patients was 11.2 months (IQR, 2.4-21). Overall mortality was 58.8% (n = 57) and 6-month mortality was 35.1% (n = 34). Nutrition assessment according to BIVA indicated a risk for cachexia and normal hydration. Patients with values of PA ≤5.52° were considered malnourished. Malnourished patients according to PA (58.8%, n = 57) had a higher risk of 6-month mortality (HR = 3.44; 95% CI, 1.51-7.84; P = .003), and each increase of 1° in PA values was associated with a reduction of 53% in 6-month mortality risk. CONCLUSIONS: The PA is an independent predictor of 6-month mortality in patients with decompensated cirrhosis. Therefore, PA may be useful to assess the nutrition status and identify patients at the highest risk of mortality in clinical practice.

Lactobacillus rhamnosusGG reduces hepatic fibrosis in a model of chronic liver disease in rats

BACKGROUND: The intestinal dysbiosis is common in chronic liver disease and can induce to inflammatory responses and mediate the collagen deposition in the liver. AIM: To evaluate the probiotic Lactobacillus rhamnosus GG (LGG) for the treatment of liver fibrosis in a model of chronic cholestatic liver disease in rats. METHODS: Male adult Wistar rats (n = 29) were submitted to common bile duct ligation (BDL groups) or manipulation of common bile duct without ligation (Ctrl groups).Two weeks after surgery, each group was randomly divided to receive 1 ml of PBS (Ctrl and BDL) or PBS containing 2.5 x 107 CFU of LGG (Ctrl-P and BDL-P) through gavages for 14 days. Euthanasia occurred 33 days after surgery when samples of blood and liver tissue were collected. RESULTS: The hepatic gene expression of Tlr4, Tnfα, IL-6, Tgfß, and metalloproteinase-2 and -9 were higher in the BDL groups in comparison to Ctrl. The ductular reaction evaluated by immunocontent of cytokeratin-7 (CK7) and the content of collagen were increased in BDL groups. Also, there was an imbalance in the antioxidant defenses (superoxide dismutase and catalase) and an increase in the oxidative stress marker sulfhydryl in BDL groups. The treatment with LGG significantly reduced gene expression of IL-6, collagen deposition, and ductular reaction in hepatic tissue of animals from BDL-P groups. CONCLUSION: The treatment with the probiotic LGG was able to reduce liver fibrosis, ductular reaction, and hepatic gene expression of IL-6 in a model of cholestatic liver disease in rats.

Experimental model of hepatic steatosis by fructose in adult zebrafish: a pilot study

Introduction: The consumption of fructose has been questioned, since its increase has led to an associated increase in steatosis caused by nonalcoholic fatty liver disease. Despite the advantages presented by the zebrafish as an animal model, at present there are no models of steatosis by fructose in adult zebrafish. The aim of this study is to establish a model of hepatic steatosis by fructose in adult zebrafish. Methods: Firstly, adult zebrafish were daily exposed to 4% or 6% fructose. Then, animals were exposed to 6% fructose every 2 days. The hepatic lipid accumulation was analyzed by Nile Red and Oil Red O staining. Results: The daily exposure to 6% fructose showed increased accumulation of hepatic lipids when compared to 4% and control groups, but the same concentration showed no difference when the exposure happened every 2 days. Conclusion: We can suggest the daily exposure to a concentration of 6% fructose can be considered as a new experimental model of adult zebrafish. (AU)

Parallel down-regulation of FOXO1, PPARγ and adiponectin mRNA expression in visceral adipose tissue of class III obese individuals.

OBJECTIVE: Adipose tissue is responsible for secretion of several cytokines that mediate systemic effects on obesity and insulin resistance. Subcutaneous abdominal adipose tissue (SAT) and visceral adipose tissue (VAT) are metabolically different and have differences in their gene expression profile. Our study evaluated the expression of adiponectin, FOXO1, PPARγ, and SIRT1 in VAT and SAT of non-obese and class III obese subjects. METHODS: The adipose tissue samples were obtained by surgery. Reverse transcripts of studied genes were determined by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Comparing the different lipid depots, adiponectin expression was lower only in VAT of obese individuals (p = 0.043); FOXO1 and PPARγ levels were decreased in VAT of both groups. When non-obese and obese were compared, only adiponectin expression was lower in SAT and in VAT of obese subjects (p = 0.004 and p = 0.002, respectively). No difference was found with regard to SIRT1 levels in VAT or SAT in both groups. FOXO1 expression in SAT of obese subjects had a negative correlation with age (r = -0.683; p = 0.029) and triglyceride serum levels (r = -0.794; p = 0.006). CONCLUSION: The decrease mRNA expression of this genes in VAT, responsible for central adiposity, may be associated with an increased risk of obesity and co-morbidities.

Microbiota e barreira intestinal: implicações para obesidade / Microbiota and intestinal barrier: implications for obesity

A epidemia da obesidade é considerada um importante problema de saúde pública na sociedade ocidental, pois ela se relaciona a comorbidades como síndrome metabólica, diabetes mellitus e hipertensão. A microbiota intestinal pode contribuir para o desenvolvimento da obesidade através do aumento da extração energética dos componentes da dieta, da lipogênese, da permeabilidade intestinal e da endotoxemia, mediada especialmente pelos lipopolissacarídeos. Estudos têm demonstrado diferenças na composição da microbiota intestinal entre indivíduos obesos e magros. Ao que parece, o aumento na proporção de Firmicutes em relação a Bacteroidetes parece estar presente na obesidade, podendo ser alterado à medida que ocorre perda de peso. Assim, o objetivo deste estudo foi revisar a literatura acerca dos mecanismos que relacionam a microbiota e a barreira intestinal ao desenvolvimento ou agravamento da obesidade (AU)

The epidemic of obesity is considered an important public health problem in the Western society and is related to comorbidities such as metabolic syndrome, diabetes mellitus, and hypertension. The intestinal microbiota may contribute to the development of obesity by increasing energy extraction from the dietary components, lipogenesis, intestinal permeability, and endotoxemia, especially mediated by lipopolysaccharides. Studies have demonstrated differences in composition of the intestinal microbiota between obese and lean individuals. Apparently, the increase in the proportion of Firmicutes in relation to Bacteroidetes seems to be present in obesity and can be changed during weight loss. The aim of this study was to review the mechanisms that relate microbiota and intestinal barrier to the development or worsening of obesity (AU)

Músculo adutor do polegar como ferramenta de avaliação nutricional em pacientes portadores do vírus da imunodeficiência humana / The thickness of the adductor pollicis muscle as a nutrition assessment tool in patients infected with the human immunodeficiency virus

Introdução: Desnutrição é frequente em pacientes portadores do HIV e está associada a pior prognóstico clínico. A espessura do músculo adutor do polegar (EMAP) é uma ferramenta de fácil e rápida aplicação, e parece estar correlacionada com medidas antropométricas. Objetivo: Avaliar a medida da EMAP para diagnosticar desnutrição em pacientes portadores do HIV. Métodos: Estudo transversal realizado em pacientes adultos portadores do HIV, atendidos no serviço de emergência de um hospital. Foram realizadas avaliação antropométrica (circunferência braquial, dobra tricipital, peso atual e altura), avaliação subjetiva global e medida da EMAP. Resultados: Foram incluídos 48 pacientes, com média de idade de 43 ± 11,16 anos, sendo 27 pacientes (56,25%) do sexo feminino. A média da EMAP foi de 9,57 ± 4,71 mm para mão direita e de 8,96 ± 3,52 mm para mão esquerda, sem diferença entre elas (p = 0,615). Coeficientes de correlação positivos (p < 0,01) foram observados somente para a espessura do músculo adutor do polegar esquerda em relação aos parâmetros antropométricos. A EMAP esquerda dos pacientes classificados como bem nutridos, através da avaliação subjetiva global, foi maior em comparação aos classificados como desnutridos (p = 0,02). Valores maiores que 11,13 mm para medida da EMAP direita e 10,08 mm para a esquerda apresentaram sensibilidade de 50% e especificidade de 93,1% e 79,3%, respectivamente, para identificação de eutrofia, segundo análise da curva ROC (AUC = 0,651 e 0,670, respectivamente). Conclusão: A EMAP esquerda pode ser utilizada para identificação do estado nutricional de pacientes portadores do HIV, atendidos em serviços de emergência (AU)

Introduction: Malnutrition is common in HIV-infected patients and is associated with a poor clinical prognosis. The thickness of the adductor pollicis muscle (TAPM) is a fast and easy tool and has a good correlation with anthropometrics measures. Objective: To evaluate the use of TAPM to diagnose malnutrition in HIV-infected patients. Methods: Cross-sectional study with adult HIV-infected patients treated in the emergency department of a hospital. Anthropometric assessment (measurement of arm circumference, triceps skinfold, weight and height), subjective global assessment, and measurement of the TAPM were performed. Results: Forty-eight patients were included. The mean age was 43 ± 11.16 years old and 27 patients (56.25%) were females. The mean TAPM was 9.57 ± 4.71 mm for the right hand and 8.96 ± 3.52 mm for the left hand, with no difference between them (p = 0.615). A positive correlation (p < 0.01) was observed only for the TAPM of the left hand in relation to the anthropometric parameters. The TAPM of the left hand of patients classified as well-nourished by subjective global assessment was higher compared with that of those classified as malnourished (p = 0.02). The ROC curve analysis showed a value of TAPM for the right hand of 11.13 mm and 10.08 mm for the left hand as a cutoff for excluding malnutrition diagnosis. Conclusion: The TAPM for the left hand can be used as anthropometric parameter in the identification of the nutritional status of HIV-infected patients treated in emergency services (AU)

Resveratrol upregulated SIRT1, FOXO1, and adiponectin and downregulated PPARγ1-3 mRNA expression in human visceral adipocytes.

BACKGROUND: The SIRT1 enzyme is involved in adipose tissue (AT) lipolysis. FOXO1 is a protein that plays a significant role in regulating metabolism. Adiponectin is an adipokine, secreted by the AT, which has been considered to have an antiobesity function. PPARγ is one of the key actors in adipocytes differentiation. This study was undertaken to investigate whether resveratrol can regulate SIRT1, FOXO1, adiponectin, PPARγ1-3, and PPARß/δ in human AT. METHODS: The effects of resveratrol were analyzed in freshly isolated adipocytes prepared from visceral fat tissue samples obtained during bariatric surgery. Genes messenger ribonucleic acid (mRNA) levels were determined by qRT-PCR. RESULTS: Ours results show that resveratrol modulates the studied genes, increasing SIRT1 (p = 0.021), FOXO1 (p = 0.001), and adiponectin (p = 0.025) mRNA expression and decreasing PPARγ1-3 (p = 0.003) mRNA in human visceral adipocytes. CONCLUSIONS: Resveratrol, in vitro and at low concentration, modulates genes that are related to lipid metabolism, possibly preventing metabolic disease in human visceral adipose tissue (VAT).

SIRT1 transcription is decreased in visceral adipose tissue of morbidly obese patients with severe hepatic steatosis.

BACKGROUND: Visceral adipose tissue is known to release greater amounts of adipokines and free fatty acids into the portal vein, being one of the most predictive factors of nonalcoholic fatty liver disease (NAFLD). Our study has the purpose to evaluate sirtuin 1 (SIRT1), adiponectin, Forkhead/winged helix (FOXO1), peroxisome proliferator-activated receptor (PPAR)gamma1-3, and PPARbeta/delta mRNA expression in morbidly obese patients in three different lipid depots: visceral (VAT), subcutaneous (SAT), and retroperitoneal (RAT). Recent studies suggest that SIRT1, a NAD(+)-dependent deacetylase, protects rats from NAFLD. METHODS: We divided the patients in two groups: those with slight or moderate steatosis (hepatic steatosis, HS) and other comprising individuals with severe steatosis associated or not with necroinflammation and fibrosis (severe hepatic steatosis, SHS). The adipose tissue depots were obtained during bariatric surgery. Total RNAs were extracted using TRIzol. The amount of genes of interest was determined by quantitative real-time polymerase chain reaction. RESULTS: When comparing the two groups of patients, a decrease in SIRT1 was observed in VAT of morbidly obese patients in SHS group (p = 0.006). The mRNA expression of the other genes showed no differences in VAT. No difference was found either in SAT or in RAT for all genes in the study. In addition, the homeostasis model assessment for insulin resistance (HOMA-IR) value was higher in SHS group compared to HS (p = 0.006). Also, our results show that the mRNA expression of SIRT1 and the value of HOMA-IR were positively correlated in VAT of SHS patients (r = 0.654; p = 0.048). CONCLUSIONS: Downregulation of SIRT1 mRNA expression in VAT of SHS could be possible impairing mitochondria biogenesis and fatty acid oxidation, promoting severe steatosis in obese patients. Our results provide a possible proof of SIRT1 protective potential in VAT against NAFLD in humans.

Terapia nutricional em crianças e adolescentes com cirrose: uma visão atual / Nutritional therapy in children and adolescents with cirrhosis: current status

A anorexia e o hipermetabolismo são aspectos clínicos importantes em crianças com cirrose. Embora muitas das complicações da cirrose sejam semelhantes àquelas encontradas em adultos, a etiologia e a história natural da progressão da doença e o tratamento clínico em pacientes pediátricos podem ser significativamente diferentes. As alterações metabólicas da doença hepática crônica agravada pela anorexia e desnutrição podem ter implicações negativas no crescimento e desenvolvimento infantil. Crianças com cirrose de evolução progressiva são frequentemente desnutridas e, no entanto, os métodos comumente empregados para avaliação nutricional têm uso limitado nestes pacientes. Mesmo que a importância do estado nutricional sobre o prognóstico destes pacientes seja clara, poucos estudos sobre a terapia nutricional nas hepatopatias da infância têm sido realizados. A avaliação nutricional em crianças com cirrose hepática deve incluir uma completa história clínica e dietética, medidas antropométricas e parâmetros laboratoriais. A recomendação nutricional na cirrose infantil pode variar de acordo com o estado nutricional, idade e quadro clínico. Como a doença hepática crônica em crianças pode impactar significativamente sobre o estado nutricional e consequentemente no crescimento e desenvolvimento, o objetivo deste artigo é revisar os aspectos clínicos e fisiopatológicos envolvidos no diagnóstico e manejo nutricional da cirrose hepática em pacientes pediátricos.

Anorexia and hypermetabolism are disorders of paramount importance in children with cirrhosis. Although many complications caused by cirrhosis in children are similar to those found in adults, the etiologic spectrum and natural history of this disease progression and its clinical management in pediatric patients may be significantly different. The metabolic changes caused by chronic liver disease aggravated by anorexia and malnutrition can affect child growth and development. Malnutrition is common in children with cirrhosis and the methods commonly used for their nutritional assessment are limited. Although the importance of the nutritional status on the prognosis of these patients is clear, there are few studies about nutritional therapy in children with cirrhosis. Nutritional assessment in children with liver cirrhosis should include full clinical and nutritional history, anthropometric measurements, and laboratory parameters. The nutritional recommendation for cirrhosis in children may vary depending on age and nutritional and clinical status. Because chronic liver disease in children may have a significant impact on nutritional status, growth, and development, the objective of this study is to review the clinical and pathophysiological aspects involved in the diagnosis and nutritional management of liver cirrhosis in children.