Dual Role of MicroRNAs in NAFLD
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Abstract:
MicroRNAs are important post-transcriptional regulators in different pathophysiological processes. They typically affect the mRNA stability or translation finally leading to the repression of target gene expression. Notably, it is thought that microRNAs are crucial for regulating gene expression during metabolic-related disorders, such as nonalcoholic fatty liver disease (NAFLD). Several studies identify specific microRNA expression profiles associated to different histological features of NAFLD, both in animal models and in patients. Therefore, specific assortments of certain microRNAs could have enormous diagnostic potentiality. In addition, microRNAs have also emerged as possible therapeutic targets for the treatment of NAFLD-related liver damage. In this review, we discuss the experimental evidence about microRNAs both as potential non-invasive early diagnostic markers and as novel therapeutic targets in NAFLD and its more severe liver complications.MicroRNAs (miRNAs) regulate their targets by triggering mRNA degradation or translational repression. The negative relationship between miRNAs and their targets suggests that the regulatory effect of a miRNA could be determined from the expression levels of its targets. Here, we investigated the relationship between miRNA activities determined by computational programs and miRNA expression levels by using data in which both mRNA and miRNA expression from the same samples were measured. We found that different from the intuitive expectation one might have, miRNA activity shows very weak correlation with miRNA expression, which indicates complex regulating mechanisms between miRNAs and their target genes. This manuscript was reviewed by an anonymous reviewer and Dr Yuriy Gusev.
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Recent cross-sectional and randomized controlled studies of small sample sizes revealed that regular exercise is effective for improving nonalcoholic fatty liver disease. However, there has been no large-scale longitudinal study addressing the effect of regular exercise on remission of nonalcoholic fatty liver disease. Thus, we investigated the impact of exercise on the natural history of nonalcoholic fatty liver disease. We analyzed 1,010 (860 men and 150 women) Japanese participants who received health checkups repeatedly over 10 years by a historical cohort study and were diagnosed with nonalcoholic fatty liver disease at baseline. Regular exercise was defined as participating in any kind of sports at least once a week. Nonalcoholic fatty liver disease was diagnosed by ultrasonographic images. During 10 years of follow-up, remission of nonalcoholic fatty liver disease was observed in 46.0% (396/860) of men and 48.7% (73/150) of women. In men, the adjusted hazard ratio of regular exercise for remission of nonalcoholic fatty liver disease was 1.46 (95% confidence interval 1.10-1.95, p = 0.010). However, this was not significant in women. Exercise at least once a week is implicated in the remission of nonalcoholic fatty liver disease in men.
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MicroRNAs are well-known strong RNA regulators modulating whole functional units in complex signaling networks. Regarding clinical application, they have potential as biomarkers for prognosis, diagnosis, and therapy. In this review, we focus on two microRNAs centrally involved in lung cancer progression. MicroRNA-21 promotes and microRNA-34 inhibits cancer progression. We elucidate here involved pathways and imbed these antagonistic microRNAs in a network of interactions, stressing their cancer microRNA biology, followed by experimental and bioinformatics analysis of such microRNAs and their targets. This background is then illuminated from a clinical perspective on microRNA-21 and microRNA-34 as general examples for the complex microRNA biology in lung cancer and its diagnostic value. Moreover, we discuss the immense potential that microRNAs such as microRNA-21 and microRNA-34 imply by their broad regulatory effects. These should be explored for novel therapeutic strategies in the clinic.
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Objective To evaluate the role of serum retinol binding protein 4(RBP4) in patients with nonalcoholic fatty liver disease(NAFLD).Methods 62 patients with nonalcoholic fatty liver disease(NAFLD group) and 60 normal subjects(normal control group) were selected.The level of serum RBP4 was measured by ELISA.Fasting blood glucose(FBG),blood lipid(TC,TG,HDL-C,LDL-C),liver function(AST,ALT),and fasting insulin(FINS) were measured.Homeostasis model assessment of insulin resistance(HOMA-IR) were calculated as well.Results The levels of RBP4,FBG,TC,TG,LDL-C,FINS,ALT,AST and HOMA-IR were higher in NAFLD patients as compared to normal controls(P0.01).The levels of Serum RBP4 were positively correlated with FBG,TC,TG,FINS and HOMA-IR(r=0.329,0.298,0.261,0.219,0.378,P0.01).Conclusion RBP4 was involved in the development of nonalcoholic fatty liver disease.Thus,RBP4 may be used as a sensitive indicator for the pathogenesis and the development of NAFLD,which can assist in early diagnosis of the disease.
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THE AIM OF REVIEW: To verify the role of nutrition in development of Nonalcoholic Fatty Liver Disease in patients with metabolic syndrome.The article contains main conceptions of etiology and pathogenesis of Nonalcoholic Fatty Liver Disease. Spesial attention gives to the role of nutrition in development of this case. The are own dates presented, which shows relationship between degree of obesity, factual nutrition and expression of morphological changes in liver in patients with Nonalcoholic Fatty Liver Disease.Nutrition mistakes in patients with Nonalcoholic Fatty Liver Disease are: excess of energy, animal proteins and fats, deficit of nutrition fibres, carbohydrates, antioxidants, vitamins B1, B2, PP. The main directions of diet in patients with Nonalcoholic Fatty Liver Disease.
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