Characterization of liver changes in ZSF1 rats, an animal model of metabolic syndrome

Background: The non-alcoholic fatty liver disease is the hepatic counterpart of the metabolic syndrome. ZSF1 rats are a metabolic syndrome animal model in which liver changes have not been described yet. Aim: The characterization of liver histological and innate immunity changes in ZSF1 rats. Methods: Five groups of rats were included (n = 7 each group): healthy Wistar-Kyoto control rats (Ctrl), hypertensive ZSF1 lean (Ln), ZSF1 obese rats with a normal diet (Ob), ZSF1 obese rates with a high-fat diet (Ob-HFD), and ZSF1 obese rats with low-intensity exercise training (Ob-Ex). The animals were sacrificed at 20 weeks of age, their livers were collected for: a) measurements of the area of steatosis, fibrosis and inflammation (histomorphological analysis); and b) innate immunity (toll-like receptor [TLR] 2, TLR4, peroxisome proliferator-activated receptor γ [PPARγ], toll interacting protein [TOLLIP]) and inflammatory marker (tumor necrosis factor-alpha [TNFvs], interleukin 1 [IL-1]) expression analysis by real-time PCR. Results: Ob, Ob-HFD and Ob-Ex were significantly heavier than Ln and Ctrl animals. Ob, Ob-HFD and Ob-Ex animals had impaired glucose tolerance and insulin resistance. ZSF1 Ob, Ob- HFD and Ob-Ex presented a higher degree of steatosis (3,5x; p < 0.05) than Ctrl or ZSF1 Ln rats. Steatohepatitis and fibrosis were not observed in any of the groups. No differences in expression were observed between Ctrl, Ln and Ob animals (except for the significantly higher expression of TOLLIP observed in the Ob vs Ln comparison). Ob-HFD and Ob-Ex rats showed increased expression of PPARγ and TOLLIP as compared to other groups. However, both groups also showed increased expression of TLR2 and TLR4. Nevertheless, this did not translate into a differential expression of TNFα or IL-1 in any of the groups. Conclusion: The ZSF1 model is associated with liver steatosis but not with steatohepatitis or a significantly increased expression of innate immunity or inflammation markers (AU)

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Characterization of liver changes in ZSF1 rats, an animal model of metabolic syndrome.

BACKGROUND: The non-alcoholic fatty liver disease is the hepatic counterpart of the metabolic syndrome. ZSF1 rats are a metabolic syndrome animal model in which liver changes have not been described yet. AIM: The characterization of liver histological and innate immunity changes in ZSF1 rats. METHODS: Five groups of rats were included (n = 7 each group): healthy Wistar-Kyoto control rats (Ctrl), hypertensive ZSF1 lean (Ln), ZSF1 obese rats with a normal diet (Ob), ZSF1 obese rates with a high-fat diet (Ob-HFD), and ZSF1 obese rats with low-intensity exercise training (Ob-Ex). The animals were sacrificed at 20 weeks of age, their livers were collected for: a) measurements of the area of steatosis, fibrosis and inflammation (histomorphological analysis); and b) innate immunity (toll-like receptor [TLR] 2, TLR4, peroxisome proliferator-activated receptor γ [PPARγ], toll interacting protein [TOLLIP]) and inflammatory marker (tumor necrosis factor-alpha [TNFα], interleukin 1 [IL-1]) expression analysis by real-time PCR. RESULTS: Ob, Ob-HFD and Ob-Ex were significantly heavier than Ln and Ctrl animals. Ob, Ob-HFD and Ob-Ex animals had impaired glucose tolerance and insulin resistance. ZSF1 Ob, Ob-HFD and Ob-Ex presented a higher degree of steatosis (3,5x; p < 0.05) than Ctrl or ZSF1 Ln rats. Steatohepatitis and fibrosis were not observed in any of the groups. No differences in expression were observed between Ctrl, Ln and Ob animals (except for the significantly higher expression of TOLLIP observed in the Ob vs Ln comparison). Ob-HFD and Ob-Ex rats showed increased expression of PPARγ and TOLLIP as compared to other groups. However, both groups also showed increased expression of TLR2 and TLR4. Nevertheless, this did not translate into a differential expression of TNFα or IL-1 in any of the groups. CONCLUSION: The ZSF1 model is associated with liver steatosis but not with steatohepatitis or a significantly increased expression of innate immunity or inflammation markers.

Role of colonic microbiota in colorectal carcinogenesis: a systematic review.

BACKGROUND AND AIM: The human colonic mucosa is populated by a wide range of microorganisms, usually in a symbiotic relation with the host. Sometimes this balance is lost and a state of dysbiosis arises, exposing the colon to different metabolic and inflammatory stimuli (according to the microbiota's changing profile). Recent findings lead to hypothesize that this unbalance may create a subclinical pro-inflammatory state that increases DNA mutations and, therefore, colorectal carcinogenesis. In this article we aim to systematically review the scientific evidence regarding colonic microbiota and its role in colorectal carcinogenesis. METHODS: Systematic review of PubMed searching results for original articles studying microbiota and colorectal cancer until November 2014. RESULTS: Thirty-one original articles studied the role of colon microbiota in colorectal carcinoma including both human and animal studies. Different and heterogeneous methods were used and different bacteria were considered. Nevertheless, some bacteria are consistently augmented (such as Fusobacteria, Alistipes, Porphyromonadaceae, Coriobacteridae, Staphylococcaceae, Akkermansia spp. and Methanobacteriales), while other are constantly diminished in colorectal cancer (such as Bifidobacterium, Lactobacillus, Ruminococcus, Faecalibacterium spp., Roseburia, and Treponema). Moreover, bacteria metabolites amino acids are increased and butyrate is decreased throughout colonic carcinogenesis. CONCLUSION: Conclusive evidence shows that colorectal carcinogenesis is associated with microbial dysbiosis. This information may be used to create new prophylactic, diagnostic and therapeutic strategies for colorectal cancer.

Role of colonic microbiota in colorectal carcinogenesis: a systematic review

BACKGROUND AND AIM: The human colonic mucosa is populated by a wide range of microorganisms, usually in a symbiotic relation with the host. Sometimes this balance is lost and a state of dysbiosis arises, exposing the colon to different metabolic and inflammatory stimuli (according to the microbiota's changing profile). Recent findings lead to hypothesize that this unbalance may create a subclinical pro-inflammatory state that increases DNA mutations and, therefore, colorectal carcinogenesis. In this article we aim to systematically review the scientific evidence regarding colonic microbiota and its role in colorectal carcinogenesis. METHODS: Systematic review of PubMed searching results for original articles studying microbiota and colorectal cancer until November 2014. RESULTS: Thirty-one original articles studied the role of colon microbiota in colorectal carcinoma including both human and animal studies. Different and heterogeneous methods were used and different bacteria were considered. Nevertheless, some bacteria are consistently augmented (such as Fusobacteria, Alistipes, Porphyromonadaceae, Coriobacteridae, Staphylococcaceae,Akkermansia spp. and Methanobacteriales), while other are constantly diminished in colorectal cancer (such as Bifidobacterium,Lactobacillus, Ruminococcus, Faecalibacterium spp., Roseburia, and Treponema). Moreover, bacteria metabolites amino acids are increased and butyrate is decreased throughout colonic carcinogenesis. CONCLUSION: Conclusive evidence shows that colorectal carcinogenesis is associated with microbial dysbiosis. This information may be used to create new prophylactic, diagnostic and therapeutic strategies for colorectal cáncer

Systematic Review of the Relation Between Intestinal Microbiota and Toll-Like Receptors in the Metabolic Syndrome: What Do We Know So Far?

INTRODUCTION: Metabolic syndrome is an emerging problem in developed countries and presents itself as a potential threat worldwide. The role of diabetes, dyslipidaemia and hepatic steatosis as pivotal components of the metabolic syndrome is well known. However, their common persistent chronic inflammation and its potential cause still elude. This systematic review aims to present evidence of the mechanisms that link the intestinal microbioma, innate immunity and metabolic syndrome. METHODS: A comprehensive research was made using PubMed database and 35 articles were selected. RESULTS: We found that metabolic syndrome is associated to increased levels of innate immunity receptors, namely, Toll-like receptors, both in intestine and systemically and its polymorphisms may change the risk of metabolic syndrome development. Microbioma dysbiosis is also present in metabolic syndrome, with lower prevalence of Bacteroidetes and increased prevalence of Firmicutes populations. The data suggest that the link between intestinal microbiota and Toll-like receptors can negatively endanger the metabolic homeostasis. CONCLUSION: Current evidence suggests that innate immunity and intestinal microbiota may be the hidden link in the metabolic syndrome development mechanisms. In the near future, this can be the key in the development of new prophylactic and therapeutic strategies to treat metabolic syndrome patients.

INTRODUÇÃO: A síndrome metabólica é, hoje, um problema emergente nos países desenvolvidos e apresenta-se como uma das principais ameaças médicas à escala global. O papel desempenhado pela diabetes, dislipidemia e a esteatose hepática, como componentes principais desta Síndrome é prontamente reconhecido. No entanto, a inflamação crónica persistente comum e as suas potenciais causas ainda não estão claramente definidas. OBJECTIVOS: Esta revisão sistemática pretende apresentar evidências dos mecanismos que interligam o microbioma intestinal, a imunidade inata e a síndrome metabólica. MÉTODOS: Uma pesquisa sistemática foi realizada, utilizando a base de dados PubMed, tendo selecionado 35 artigos para a elaboração desta revisão. RESULTADOS: A síndrome metabólica está claramente associada a níveis aumentados de expressão dos receptores da imunidade inata, nomeadamente, os receptores da família Toll-like receptors, quer no tecido intestinal, quer sistemicamente, e diferentes polimorfismos parecem ser responsáveis por diferentes riscos de desenvolver esta doença. Por outro lado, a disbiose do microbioma intestinal está também presente na síndrome metabólica, com a presença de Bacteriodetes em menor prevalência e com aumento das populações de Firmicutes. Os resultados sugerem ainda que a ligação entre a microbiota intestinal e os receptores da imunidade inata possa negativamente comprometer a homeostasia metabólica, de forma semelhante à evidenciada nesta síndrome. CONCLUSÕES: Evidência actual sugere e suporta que a imunidade inata e a microbiota intestinal possam ser a ligação pivô nos mecanismos de desenvolvimento da síndrome metabólica. Num futuro próximo, esta pode ser a chave para o desenvolvimento de novas estratégias profiláticas e terapêuticas para a síndrome metabólica.