Role of LPS/TLR4 signaling pathway in nonalcoholic fatty liver disease

A ginsenoside F2-enhanced mixture (SGL 121) increases the content of ginsenoside F2 by biotransformation. In the present study, we investigated the effect of SGL 121 on nonalcoholic fatty liver disease (NAFLD) in vitro and in vivo. High-fat, high-carbohydrate-diet (HFHC)-fed mice were administered SGL 121 for 12 weeks to assess its effect on improving NAFLD. In HepG2 cells, SGL 121 acted as an antioxidant, a hepatoprotectant, and had an anti-lipogenic effect. In NAFLD mice, SGL 121 significantly improved body fat mass; levels of hepatic triglyceride (TG), hepatic malondialdehyde (MDA), serum total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL); and activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In HepG2 cells, induced by oxidative stress, SGL 121 increased cytoprotection, inhibited reactive oxygen species (ROS) production, and increased antioxidant enzyme activity. SGL 121 activated the Nrf2/HO-1 signaling pathway and improved lipid accumulation induced by free fatty acids (FFA). Sterol regulatory element-binding protein-1 (SREBP-1) and fatty acid synthase (FAS) expression was significantly reduced in NAFLD-induced liver and HepG2 cells treated with SGL 121. Moreover, SGL 121 activated adenosine monophosphate-activated protein kinase (AMPK), which plays an important role in the regulation of lipid metabolism. The effect of SGL 121 on the improvement of NAFLD seems to be related to its antioxidant effects and activation of AMPK. In conclusion, SGL 121 can be potentially used for the treatment of NAFLD.

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THE ROLE OF MACRONUTRIENTS IN THE PROGRESSION OF NONALCOHOLIC FATTY LIVER DISEASE (NAFLD). PRELIMINARY DATA ON 30 OBESE PATIENTS

Digestive and Liver Disease ◽

10.1016/s1590-8658(09)60287-5 ◽

2009 ◽

Vol 41 ◽

pp. S110

Author(s):

G. Ricci ◽

E. Canducci ◽

A. Rossi ◽

G. Bersani ◽

E. Ricci ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Preliminary Data ◽

Fatty Liver Disease ◽

Obese Patients ◽

Nonalcoholic Fatty Liver

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

PLoS ONE ◽

10.1371/journal.pone.0088005 ◽

2014 ◽

Vol 9 (2) ◽

pp. e88005 ◽

Cited By ~ 84

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

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Role of folate in nonalcoholic fatty liver disease

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2016-0681 ◽

2017 ◽

Vol 95 (10) ◽

pp. 1141-1148 ◽

Cited By ~ 20

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.

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

10.21203/rs.2.15906/v1 ◽

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.

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