scholarly journals The Role of Bone Morphogenetic Protein 9 in Nonalcoholic Fatty Liver Disease in Mice

2021 ◽  
Vol 11 ◽  
Author(s):  
Qin-Juan Sun ◽  
Ling-Yan Cai ◽  
Jie Jian ◽  
Ya-Lu Cui ◽  
Chen-Kai Huang ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Fatty Liver Disease ◽  
Mouse Liver ◽  
Tolerance Test ◽  
Chromatin Accessibility ◽  
Rna Seq ◽  
Nonalcoholic Fatty Liver ◽  
Morphogenetic Protein ◽  
Bone Morphogenetic Protein 9

Background and Aims: It’s reported that bone morphogenetic protein 9 (BMP9) played an important role in lipid and glucose metabolism, but the role of BMP9 in nonalcoholic fatty liver disease (NAFLD) is unclear. Here, we evaluated the therapeutic efficacy of recombined BMP9 in NAFLD mice and investigated the potential mechanism.Methods: The effects of recombinant BMP9 on NAFLD were assessed in HFD-induced NAFLD mice. C57BL/6 mice were administrated with high-fat diet (HFD) for 12 weeks. In the last 4 weeks, mice were treated with PBS or recombined BMP9 once daily. Insulin sensitivity was evaluated by glucose tolerance test (GTT) and insulin tolerance test (ITT) at the end of the 12th week. Then NAFLD related indicators were assessed by a variety of biological methods, including histology, western blotting, real-time PCR, RNA-seq and assay for transposase-accessible chromatin using sequencing (ATAC-seq) analyses.Results: BMP9 reduced obesity, improved glucose metabolism, alleviated hepatic steatosis and decreased liver macrophages infiltration in HFD mice. RNA-seq showed that Cers6, Cidea, Fabp4 involved in lipid and glucose metabolism and Fos, Ccl2, Tlr1 involved in inflammatory response downregulated significantly after BMP9 treatment in HFD mouse liver. ATAC-seq showed that chromatin accessibility on promoters of Cers6, Fabp4, Ccl2 and Fos decreased after BMP9 treatment in HFD mouse liver. KEGG pathway analysis of dysregulated genes in RNA-seq and integration of RNA-seq and ATAC-seq showed that TNF signaling pathway and Toll-like receptor signaling pathway decreased in BMP9 treated HFD mouse liver.Conclusion: Our data revealed that BMP9 might alleviate NAFLD via improving glucose and lipid metabolism, decreasing inflammatory response and reshaping chromatin accessibility in HFD mouse liver. BMP9 downregulate genes related to lipid metabolism, glucose metabolism and inflammation expression, at least partially via decreasing promoter chromatin accessibility of Cers6, Fabp4, Fos and Tlr1. BMP9 may also reduce the expression of liver Ccl2, thereby changing the number or composition of liver macrophages, and ultimately reducing liver inflammation. The effect of BMP9 on NAFLD might be all-round, and not limit to lipid and glucose metabolism. Therefore, the underlying mechanism needs to be studied in detail further.

scholarly journals Role of Docosahexaenoic Acid Treatment in Improving Liver Histology in Pediatric Nonalcoholic Fatty Liver Disease

PLoS ONE ◽  
2014 ◽  
Vol 9 (2) ◽  
pp. e88005 ◽  
Author(s):  
Valerio Nobili ◽  
Guido Carpino ◽  
Anna Alisi ◽  
Rita De Vito ◽  
Antonio Franchitto ◽  
...  
Keyword(s):  
Liver Disease ◽  
Docosahexaenoic Acid ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Acid Treatment ◽  
Liver Histology ◽  
Nonalcoholic Fatty Liver

scholarly journals Role of folate in nonalcoholic fatty liver disease

2017 ◽  
Vol 95 (10) ◽  
pp. 1141-1148 ◽  
Author(s):  
Victoria Sid ◽  
Yaw L. Siow ◽  
Karmin O
Keyword(s):  
Type 2 Diabetes ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Serum Folate ◽  
Nonalcoholic Fatty Liver ◽  
Obesity And Diabetes

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of chronic liver conditions that are characterized by steatosis, inflammation, fibrosis, and liver injury. The global prevalence of NAFLD is rapidly increasing in proportion to the rising incidence of obesity and type 2 diabetes. Because NAFLD is a multifaceted disorder with many underlying metabolic abnormalities, currently, there is no pharmacological agent that is therapeutically approved for the treatment of this disease. Folate is a water-soluble B vitamin that plays an essential role in one-carbon transfer reactions involved in nucleic acid biosynthesis, methylation reactions, and sulfur-containing amino acid metabolism. The liver is the primary organ responsible for storage and metabolism of folates. Low serum folate levels have been observed in patients with obesity and diabetes. It has been reported that a low level of endogenous folates in rodents perturbs folate-dependent one-carbon metabolism, and may be associated with development of metabolic diseases such as NAFLD. This review highlights the biological role of folate in the progression of NAFLD and its associated metabolic complications including obesity and type 2 diabetes. Understanding the role of folate in metabolic disease may position this vitamin as a potential therapeutic for NAFLD.

scholarly journals Efficacy of Ursodeoxycholic Acid in Nonalcoholic Fatty Liver Disease: An Updated Meta-Analysis of Randomized Controlled Trials

2019 ◽  
Author(s):  
Wenyue Zhang ◽  
Yao Tang ◽  
Juan Huang ◽  
Hong Ren ◽  
Yixuan Yang ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Ursodeoxycholic Acid ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Total Bilirubin ◽  
Meta Analysis ◽  
Nonalcoholic Fatty Liver ◽  
Randomized Controlled

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is a kind of chronic liver disease among general population. Recent years, more and more new experiments have made the role of ursodeoxycholic acid (UDCA) become clearer. In this meta-analysis, we analyzed the efficacy of ursodeoxycholic acid (UDCA) for the treatment of nonalcoholic fatty liver disease (NAFLD). Methods We searched the Web of Science, Pubmed, Embase and Cochrane library databases for relavent studies published before March 1, 2019. We examined 134 randomized controlled trials (RCTs) that investigated the effectiveness of UDCA in NAFLD against placebo or other treatments. Next, we conducted meta-analysis by Stata(version 12.0) to examine the change among several indices: Alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), Alkaline phosphatase (AP), total bilirubin and albumin. Results Following the application of different inclusion and exclusion criteria, 9 articles with 1106 participants were finally selected. The forest plot displayed that UDCA treatment can significantly decrease the ALT levels among the NAFLD patients (SMD=0.17,95%CI [0.03 to 0.3], P=0.07). However, UDCA treatment did not significantly affect the AST, GGT, AP, total bilirubin and albumin levels. Further, the subgroup analyses suggested the significant role of UDCA treatment in different geographical regions, age group and treatment duration (P=0.003 in people from Europe, P=0.001 in people older than 50 years and P=0.008 in longer duration(>6 months)). Conclusion In this study, several indices we analyzed among 9 articles. UDCA treatment was found beneficial in lowering the ALT levels in NAFLD patients. The remaining indices like AST, GGT, AP showed non-significant changes in this analysis. This could be attributed for the insufficient number of trials because all parameters were not analyzed in each individual RCT. Therefore, future meta-analysis will be required to fully confirm and validate the efficacy of UDCA in NAFL.

scholarly journals Role of insulin resistance in the pathogenesis of nonalcoholic fatty liver disease

2010 ◽  
Vol 18 (30) ◽  
pp. 3175
Author(s):  
Bing-Fang Wang ◽  
Pei-Ying Tian ◽  
Kun Feng ◽  
Fu-Rong Wu ◽  
Yong-Gao Lu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver

scholarly journals Role of Bile Acids in Dysbiosis and Treatment of Nonalcoholic Fatty Liver Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Caihua Wang ◽  
Chunpeng Zhu ◽  
Liming Shao ◽  
Jun Ye ◽  
Yimin Shen ◽  
...  
Keyword(s):  
Liver Disease ◽  
Bile Acid ◽  
Gut Microbiota ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Bile Acids ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver ◽  
Bile Acid Receptors

Nonalcoholic fatty liver disease (NAFLD) is a major health threat around the world and is characterized by dysbiosis. Primary bile acids are synthesized in the liver and converted into secondary bile acids by gut microbiota. Recent studies support the role of bile acids in modulating dysbiosis and NAFLD, while the mechanisms are not well elucidated. Dysbiosis may alter the size and the composition of the bile acid pool, resulting in reduced signaling of bile acid receptors such as farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5). These receptors are essential in lipid and glucose metabolism, and impaired bile acid signaling may cause NAFLD. Bile acids also reciprocally regulate the gut microbiota directly via antibacterial activity and indirectly via FXR. Therefore, bile acid signaling is closely linked to dysbiosis and NAFLD. During the past decade, stimulation of bile acid receptors with their agonists has been extensively explored for the treatment of NAFLD in both animal models and clinical trials. Early evidence has suggested the potential of bile acid receptor agonists in NAFLD management, but their long-term safety and effectiveness need further clarification.

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