Physical training effect in obese mice with non-alcoholic fatty liver disease: aspects related to insulin resistance and inflammation

A Doença Hepática Gordurosa Não Alcoólica (DHGNA), compreende um amplo espectro de condições que variam desde uma esteatose simples, às condições mais graves como Esteatohepatite Não Alcoólica (EHNA) fibrose hepática e cirrose. Entre os fatores relacionados a progressão da doença, a inflamação e a resistência à insulina são apontados como fundamentais. Além disso, o recente aumento considerável no número de casos desta doença se deve em parte, ao comportamento sedentário e reduções drásticas no nível de atividade física. Mudanças nos hábitos de vida são essenciais para prevenção e controle da DHGNA. Objetivo: Avaliar o efeito do treinamento físico aeróbio de 8 semanas em aspectos relacionados com a resistência à insulina e resposta inflamatória em camundongos obesos com DHGNA Métodos: Foram utilizados 14 camundongos ob/ob com 6 semanas de vida divididos em dois grupos de estudo: sedentário e treinado. Os animais do grupo treinado realizaram 5 sessões semanais de 60 minutos de treinamento físico em esteira rolante com intensidade constante de 60% da velocidade máxima obtida através do teste de esforço físico. Os animais do grupo sedentário não realizavam o treinamento físico. Após o período de 8 semanas, os animais foram submetidos a eutanásia e amostras de tecido hepático e pancreático, foram coletadas para verificar características histológicas, avaliação dos genes relacionados com a resposta inflamatória e resistência à insulina. Foram coletados os tecidos adiposos para verificar a diferença na quantidade de gordura encontrada em cada região do animal. Para obtenção do material genético, foi realizado a extração do RNA por TRIzol® e após a verificação de quantidade e integridade do material, foi realizado a reação em cadeia polimerase, através do equipamento Rotor Gene RG - 3000. Foi utilizado o teste-t, ANOVA one way e pós teste de Bonferroni de comparações múltiplas para os dados paramétricos e testes de Mann-Whitney com pós-teste Dunn\'s de comparações múltiplas para dados não paramétricos. Em relação aos escores histológicos foi utilizado o teste Qui-quadrado com exato de Fisher. Foram consideradas variáveis significativas quando o p < 0,05. Todos os cálculos e análises foram realizados com o software GraphPad Prism V6.0 (GraphPad Software Inc). Resultados: Foram observadas diferenças significantes para peso corporal (p=0.008), evolução de peso (p=0.03), consumo de ração (p < 0.0001) além de diminuição no conteúdo de gordura da região retroperitonial (p=0.03). Além disso, foram observadas diferenças significantes para velocidade pico (p=0.03), distância (p=0.01) e tempo (p=0.006). A análise histológica não mostrou diferenças estatísticas entre os grupos em ambos os órgãos. Nas análises de expressão gênica, foram observadas diferenças significantes nos genes de GLUT-2 (p=0.03), IL-6 (p= 0.01) e IL-10 (p=0.03) hepáticos. Em relação ao pâncreas, foi observada diferença significante para os genes de IRS-2 (p=0.004), GLUT-2 (p=0.03), IL-6 (p=0.002) e IL-10 (p=0.008). Conclusão: Um protocolo de treinamento físico de 8 semanas foi capaz de atenuar o ganho de peso corporal, consumo alimentar e gerar efeitos positivos na expressão de genes relacionados com resistência à insulina e inflamação no fígado e pâncreas de camundongos ob-obNon-alcoholic Fatty Liver Disease (NAFLD) encompasses a wide spectrum of pathologies from hepatic steatosis, nonalcoholic steatohepatitis (NASH), fibrosis and cirrhosis. Insulin resistance and inflammation are reported as the main factors for disease progression. Moreover, the increase in the number of new cases of NAFLD can be explained by sedentary behavior and drastic reductions in physical activity levels, therefore, lifestyle modifications are essencial for prevention and control of the disease. Objective: Evaluate the effect of 8 weeks of aerobic training on insulin resistance and inflammatory response in obese mice (ob/ob) with NAFLD. Methods: Male ob/ob mice were randomly divided into sedentary (n=7) and trained (n=7) groups. Aerobic training consisted of 5 weekly sessions, 60 min per session at 60% of the maximum speed of the running test. Hepatic and pancreatic samples were collected to evaluate histological features and gene expression associated with insulin resistance and inflammatory response after 8 week experiment protocol. RNA was performed by TRIzol®. PCR experiments were performed using the Rotor Gene RG - 3000. Parametric data were assessed by t-test, ANOVA one way and Bonferroni test for multiple comparisons. Non-parametric data were assessed by the Mann-Whitney tests with Dunn\'s post-test of multiple comparisons. Histological analysis was assessed by chi-square test with Fisher\'s exact test. Significant variables were considered when p < 0.05. All the analyzes were performed by GraphPad Prism V6.0 software (GraphPad Software Inc). Results: Reductions in body weight (p = 0.008), weight evolution (p = 0.03), food intake (p < 0.0001) and fat content were observed in trained group. Moreover, the trained group showed better results in peak velocity (p=0.03) physical effort tolerance (p=0.006) and distance (p=0.01). Histological analysis showed no statistical differences between groups in both organs. Gene expression showed differences in IL-6 (p= 0.01), IL-10 (p=0.03) and GLUT-2 (p=0.03) in hepatic analysis, between groups. Pancreatic gene expression showed difference between groups in IRS-2 (p=0.004), GLUT-2 (p=0.03), IL-6 (p=0.002) and IL-10 (p=0.008) analysis. Conclusions: An 8-week physical training protocol was able to attenuate body weight gain, food intake and generate positive effects on gene expression related to insulin resistance and inflammation in both liver and pancreas of ob/ob mic

Fatty Pancreas: Disease or Finding?

Despite a growing number of investigative studies on pancreatic fat deposition, there remains no clear indication regarding the clinical relevance of fat infiltration in the pancreas, also called fatty pancreas (FP). An individual’s body weight is correlated with their pancreatic weight. Moreover, lipid infiltration causes disorders that compromise not only morphology but also metabolic functions. Fat infiltration leads to insulin resistance, type II diabetes mellitus, and pancreatic cancer; however, knowledge about pancreatic fat content and aspects related to the clinical profile remains unclear in the literature. The present review describes the current knowledge of FP, including its pathophysiology and clinical implications, as well as lifestyle changes in FP

Biochemical markers and levels of physical activity related to the hepatic condition of patients infected by the hepatitis C virus

Study aim: The study is quantitative, with a cross-sectional comparison design, and aimed to verify the association between physical activity (PA) levels and biochemical markers linked to liver function of patients infected with hepatitis C virus (HCV). Material and methods: The following biochemical variables were analyzed: alanine aminotransferases (ALT), gamma-glutamyl transpeptidase (γGt), and alkaline phosphatase (FA), these being good markers for hepatic damage, besides glycemia, HDL, LDL, and triglycerides. The International Physical Activity Questionnaire (IPAQ), short version, was used to evaluate the lev­els of physical activity, being classified as active and physically inactive. Results: The sample consisted of 84 individuals aged 56.2 ± 11.6 years; there was a predominance of males, patients with dif­ferent socioeducational patterns and those followed up for more than 6 months in the hepatology service with positive serology for HCV and HCV (RNA+), attending the Institute of Liver and Transplants of Pernambuco (IFP). The results obtained in this study indicate smaller values of the median with maximum and minimum scores of the analyzed parameters in patients consid­ered to be physically active (ALT: p = 0.43, FA: p = 0.86 and γGt: p = 0.15, glycemia: p = 0.22, LDL: p = 0.58, HDL: P = 0.004, triglycerides: p = 0.47), in comparison with the physically inactive patients. It is concluded that patients who have a higher level of physical activity present lower values of biochemical markers, positively affecting their hepatic condition. Conclusions: There was only a significant difference in the HDL variable, but the patients with a lower level of physical activ­ity showed greater values in general, less in the triglyceride variability. In order to test these and other important variables and improve the quality of life and health by a more direct method

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P &lt; 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)