scholarly journals Distinguishing NASH Histological Severity Using a Multiplatform Metabolomics Approach

Metabolites ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 168 ◽  
Author(s):  
George N. Ioannou ◽  
G. A. Nagana Gowda ◽  
Danijel Djukovic ◽  
Daniel Raftery
Keyword(s):  
Nmr Spectroscopy ◽  
Fatty Liver ◽  
Metabolic Pathways ◽  
Metabolite Profile ◽  
Protective Effects ◽  
Serum Samples ◽  
Multivariate Statistical ◽  
Nonalcoholic Fatty Liver ◽  
Early Fibrosis ◽  
Analytical Platforms

Nonalcoholic fatty liver disease (NAFLD) is categorized based on histological severity into nonalcoholic fatty liver (NAFL) or nonalcoholic steatohepatitis (NASH). We used a multiplatform metabolomics approach to identify metabolite markers and metabolic pathways that distinguish NAFL from early NASH and advanced NASH. We analyzed fasting serum samples from 57 prospectively-recruited patients with histologically-proven NAFLD, including 12 with NAFL, 31 with early NASH and 14 with advanced NASH. Metabolite profiling was performed using a combination of liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) spectroscopy analyzed with multivariate statistical and pathway analysis tools. We targeted 237 metabolites of which 158 were quantified. Multivariate analysis uncovered metabolite profile clusters for patients with NAFL, early NASH, and advanced NASH. Also, multiple individual metabolites were associated with histological severity, most notably spermidine which was more than 2-fold lower in advanced fibrosis vs. early fibrosis, in advanced NASH vs. NAFL and in advanced NASH vs. early NASH, suggesting that spermidine exercises a protective effect against development of fibrosing NASH. Furthermore, the results also showed metabolic pathway perturbations between early-NASH and advanced-NASH. In conclusion, using a combination of two reliable analytical platforms (LC-MS and NMR spectroscopy) we identified individual metabolites, metabolite clusters and metabolic pathways that were significantly different between NAFL, early-NASH, and advanced-NASH. These differences provide mechanistic insights as well as potentially important metabolic biomarker candidates that may noninvasively distinguish patients with NAFL, early-NASH, and advanced-NASH. The associations of spermidine levels with less advanced histology merit further assessment of the potential protective effects of spermidine in NAFLD.

scholarly journals Green Tea and Epigallocatechin Gallate (EGCG) for the Management of Nonalcoholic Fatty Liver Diseases (NAFLD): Insights into the Role of Oxidative Stress and Antioxidant Mechanism

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1076
Author(s):  
Guoyi Tang ◽  
Yu Xu ◽  
Cheng Zhang ◽  
Ning Wang ◽  
Huabin Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Fatty Liver ◽  
Green Tea ◽  
Liver Diseases ◽  
Randomized Clinical Trials ◽  
Epigallocatechin Gallate ◽  
Protective Effects ◽  
Nonalcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver Diseases ◽  
Underlying Mechanisms

Nonalcoholic fatty liver diseases (NAFLD) represent a set of liver disorders progressing from steatosis to steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma, which induce huge burden to human health. Many pathophysiological factors are considered to influence NAFLD in a parallel pattern, involving insulin resistance, oxidative stress, lipotoxicity, mitochondrial dysfunction, endoplasmic reticulum stress, inflammatory cascades, fibrogenic reaction, etc. However, the underlying mechanisms, including those that induce NAFLD development, have not been fully understood. Specifically, oxidative stress, mainly mediated by excessive accumulation of reactive oxygen species, has participated in the multiple NAFLD-related signaling by serving as an accelerator. Ameliorating oxidative stress and maintaining redox homeostasis may be a promising approach for the management of NAFLD. Green tea is one of the most important dietary resources of natural antioxidants, above which epigallocatechin gallate (EGCG) notably contributes to its antioxidative action. Accumulative evidence from randomized clinical trials, systematic reviews, and meta-analysis has revealed the beneficial functions of green tea and EGCG in preventing and managing NAFLD, with acceptable safety in the patients. Abundant animal and cellular studies have demonstrated that green tea and EGCG may protect against NAFLD initiation and development by alleviating oxidative stress and the related metabolism dysfunction, inflammation, fibrosis, and tumorigenesis. The targeted signaling pathways may include, but are not limited to, NRF2, AMPK, SIRT1, NF-κB, TLR4/MYD88, TGF-β/SMAD, and PI3K/Akt/FoxO1, etc. In this review, we thoroughly discuss the oxidative stress-related mechanisms involved in NAFLD development, as well as summarize the protective effects and underlying mechanisms of green tea and EGCG against NAFLD.

scholarly journals Quantitative genome-scale analysis of human liver reveals dysregulation of glycosphingolipid pathways in progressive nonalcoholic fatty liver disease

2021 ◽  
Author(s):  
Partho Sen ◽  
Olivier Govaere ◽  
Tim Sinioja ◽  
Aidan McGlinchey ◽  
Dawei Geng ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Metabolic Pathways ◽  
Fatty Liver Disease ◽  
Human Liver ◽  
Integrative Approach ◽  
Metabolomics Data ◽  
Nonalcoholic Fatty Liver ◽  
Genome Scale

ABSTRACTNonalcoholic fatty liver disease (NAFLD) is a well defined chronic liver diseases closely related with metabolic disorders. The prevalence of NAFLD is rapidly increasing worldwide, while the pathology and the underlying mechanisms driving NAFLD are not fully understood. In NAFLD, a series of metabolic changes takes place in the liver. However, the alteration of the metabolic pathways in the human liver along the progression of NAFLD, i.e., the transition from nonalcoholic steatosis (NAFL) to steatohepatitis (NASH) through cirrhosis remains to be discovered. Here, we sought to examine the metabolic pathways of the human liver across the full histological spectrum of NAFLD. We analyzed the whole liver tissue transcriptomic (RNA-Seq) and serum metabolomics data obtained from a large, prospectively enrolled cohort of histologically characterized patients derived from the European NAFLD Registry (n=206), and developed genome-scale metabolic models (GEMs) of human hepatocytes at different stages of NAFLD. The integrative approach employed in this study has enabled us to understand the regulation of the metabolic pathways of human liver in NAFL, and with progressive NASH-associated fibrosis (F0–F4). Our study identified several metabolic signatures in the liver and blood of these patients, specifically highlighting the alteration of vitamins (A, E) and glycosphingolipids (GSLs), and their link with complex glycosaminoglycans (GAGs) in advanced fibrosis. The study provides insights into the underlying pathways of the progressive fibrosing steatohepatitis. Furthermore, by applying genome-scale metabolic modeling (GSMM), we were able to identify the metabolic differences among carriers of widely validated genetic variants associated with NAFLD / NASH disease severity in three genes (PNPLA3, TM6SF2 and HSD17B13).

Polyphenol intakes and risk of impaired lipid profile, elevated hepatic enzymes and nonalcoholic fatty liver disease

2019 ◽  
Vol 49 (5) ◽  
pp. 903-910 ◽  
Author(s):  
Mehrnaz Nikkhah-Bodaghi ◽  
Matin Ghanavati ◽  
Azita Hekmatdoost
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Lipid Profile ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Separate Analysis ◽  
Protective Effects ◽  
Hepatic Enzymes ◽  
Content Type ◽  
Nonalcoholic Fatty Liver

PurposePolyphenols are plant-derived bioactive compounds with some known hepato-protective effects. The purpose of this study is to evaluate the association between polyphenol consumption and risk of nonalcoholic fatty liver disease (NAFLD) and its related conditions such as impaired lipid profile and elevated hepatic enzymes.Design/methodology/approachA total of 196 NAFLD patients and 803 controls were enrolled in this case-control study. Biochemical and anthropometric measurements as well as polyphenol consumption during the previous year were assessed.FindingsIn unadjusted model, participants who consumed the third and fourth quartiles of polyphenols intake were less likely to have NAFLD in comparison to those who consumed the first quartile [odds ratio, OR: 0.48; 95 per cent confidence interval, CI: (0.30-0.77) and OR: 0.62; 95 per cent CI: (0.40-0.96), respectively]. In separate analysis of genders, this effect was seen only in male participants [OR: 0.29; 95 per cent CI: (0.14-0.58) and OR: 0.21; 95 per cent CI (0.10-0.42), respectively], and the association remained significant after adjustment for energy, body mass index, age and smoking.Originality/valueHigher total polyphenol intake is associated with a decreased risk of NAFLD. Prospective studies are needed to confirm these results.

scholarly journals Protective Effects of MitoTEMPO on Nonalcoholic Fatty Liver Disease via Regulating Myeloid-Derived Suppressor Cells and Inflammation in Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Jiayuan Wu ◽  
Li Zheng ◽  
Juanfen Mo ◽  
Xiujuan Yao ◽  
Chenliang Fan ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Calcium Binding ◽  
Fatty Liver Disease ◽  
Calcium Binding Protein ◽  
Protective Effects ◽  
Nonalcoholic Fatty Liver ◽  
S100 Calcium Binding Protein ◽  
Protein Expressions

MitoTEMPO, a mitochondrial antioxidant, has protective effects on liver-related diseases. However, the role of MitoTEMPO on nonalcoholic fatty liver disease (NAFLD) and its possible mechanisms are largely unknown. Here, we investigated the effects of MitoTEMPO on NAFLD using high fat diet- (HFD-) induced obese mice as animal models. MitoTEMPO was intraperitoneally injected into HFD mice. Liver morphological changes were observed by H&E and Oil Red O staining, and the frequency of MDSCs in peripheral blood was analyzed by flow cytometry. Moreover, real-time quantitative PCR, western blot, and immunohistochemistry were conducted to detect the mRNA and protein expressions in the liver tissues. The results showed that the hepatic steatosis in liver tissues of HFD mice injected with MitoTEMPO was significantly ameliorated. Additionally, MitoTEMPO reduced the frequency of CD11b+Gr-1+ MDSCs in peripheral circulation and decreased Gr-1+ cell accumulation in the livers. Further studies demonstrated that MitoTEMPO administration suppressed the mRNA and protein expressions of MDSC-associated proinflammatory mediators, such as monocyte chemoattractant protein-1 (MCP-1), S100 calcium-binding protein A8 (S100A8), and S100 calcium-binding protein A9 (S100A9). Our results suggest that MitoTEMPO appears to be a potential chemical compound affecting certain immune cells and further ameliorates inflammation in obese-associated NAFLD.

scholarly journals Da-Chai-Hu Decoction Ameliorates High Fat Diet-Induced Nonalcoholic Fatty Liver Disease Through Remodeling the Gut Microbiota and Modulating the Serum Metabolism

2020 ◽  
Vol 11 ◽  
Author(s):  
Huantian Cui ◽  
Yuting Li ◽  
Yuming Wang ◽  
Lulu Jin ◽  
Lu Yang ◽  
...  
Keyword(s):  
Liver Disease ◽  
16S Rrna ◽  
Gut Microbiota ◽  
Fatty Liver ◽  
Metabolic Pathways ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
High Fat ◽  
Nonalcoholic Fatty Liver ◽  
Rrna Sequencing

The dysbiosis in gut microbiota could affect host metabolism and contribute to the development of nonalcoholic fatty liver disease (NAFLD). Da-Chai-Hu decoction (DCH) has demonstrated protective effects on NAFLD, however, the exact mechanisms remain unclear. In this study, we established a NAFLD rat model using a high fat diet (HFD) and provided treatment with DCH. The changes in gut microbiota post DCH treatment were then investigated using 16S rRNA sequencing. Additionally, serum untargeted metabolomics were performed to examine the metabolic regulations of DCH on NAFLD. Our results showed that DCH treatment improved the dyslipidemia, insulin resistance (IR) and ameliorated pathological changes in NAFLD model rats. 16S rRNA sequencing and untargeted metabolomics showed significant dysfunction in gut microbiota community and serum metabolites in NAFLD model rats. DCH treatment restored the dysbiosis of gut microbiota and improved the dysfunction in serum metabolism. Correlation analysis indicated that the modulatory effects of DCH on the arachidonic acid (AA), glycine/serine/threonine, and glycerophospholipid metabolic pathways were related to alterations in the abundance of Romboutsia, Bacteroides, Lactobacillus, Akkermansia, Lachnoclostridium and Enterobacteriaceae in the gut microflora. In conclusion, our study revealed the ameliorative effects of DCH on NAFLD and indicated that DCH’s function on NAFLD may link to the improvement of the dysbiosis of gut microbiota and the modulation of the AA, glycerophospholipid, and glycine/serine/threonine metabolic pathways.

Hepatic AMP Kinase as a Potential Target for Treating Nonalcoholic Fatty Liver Disease: Evidence from Studies of Natural Products

2018 ◽  
Vol 25 (8) ◽  
pp. 889-907 ◽  
Author(s):  
Gang Xu ◽  
Kaixun Huang ◽  
Jun Zhou
Keyword(s):  
Natural Products ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Adenosine Monophosphate ◽  
Protective Effects ◽  
Nonalcoholic Fatty Liver ◽  
Ampk Signaling ◽  
Downstream Effectors

Background: Nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease, is the leading cause of cryptogenic cirrhosis and has consistently been implicated in related metabolic disorders, such as dyslipidemia and type 2 diabetes (T2D). However, the pathogenesis of NAFLD remains to be elucidated, and no established therapeutic regimens for treating NAFLD exist. Adenosine monophosphate (AMP)-activated protein kinase (AMPK), the main cellular energy sensor, has been implicated as a key regulator of hepatic lipid and glucose metabolism. Recently, emerging evidence indicates that many plant-derived natural products are capable of ameliorating NAFLD by targeting AMPK. Methods: The published literature in PubMed relating to this topic was searched through June 2016. Results: Significant advances have been made with respect to understanding the protective effects of plant-derived natural products against NAFLD. A variety of natural products, including alkaloids (berberine, demethyleneberberine, nicotine, caffeine, etc.), polyphenols (resveratrol, puerarin, curcumin, caffeic acid, etc.) and other compounds (β- caryophyllene, gastrodin, compound K, betulinic acid, etc.), have demonstrated promising results in preclinical studies. Mechanistic studies of these compounds have focused on their activation of AMPK and its downstream effectors involved in lipid metabolism. Conclusion: The findings of this review confirm that plant-derived natural products capable of activating the AMPK signaling pathway are potential therapeutic agents for NAFLD.

scholarly journals Serum and Brain Metabolomic Variations Reveal Perturbation of Sleep Deprivation on Rats and Ameliorate Effect of Total Ginsenoside Treatment

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Xiao-jun Gou ◽  
Fang Cen ◽  
Zi-quan Fan ◽  
Ying Xu ◽  
Hong-yi Shen ◽  
...  
Keyword(s):  
Sleep Deprivation ◽  
Brain Tissue ◽  
Panax Ginseng ◽  
Well Being ◽  
Metabolite Profile ◽  
Control Group ◽  
Protective Effects ◽  
Serum Samples ◽  
Tissue Samples ◽  
And Control

Sleep loss or sleep deprivation (SD) refers to shorter sleep than average baseline need, and SD has been a serious problem of modern societies which affects health and well-being.Panax ginsengis a well-known traditional Chinese medicine (TCM). Our previous study has demonstrated that total ginsenosides (GS), the extracts fromPanax ginseng, could effectively improve cognition and behavior on SD rats. However, little is known about its metabolomic study. In this study, serum and brain metabolomic method based on gas chromatography coupled with mass spectrometry (GC/MS) was employed to evaluate the efficacy and study the mechanism of GS on a rat model of SD. With pattern recognition analysis of serum and brain tissue metabolite profile, a clear separation of the model group and control group was acquired for serum and brain tissue samples; the MGS (model + GS) group showed a tendency of recovering when compared to control group, which was consistent with behavioral and biochemical parameters. 39 and 40 potential biomarkers of brain tissues and serum samples, respectively, were identified and employed to explore the possible mechanism. Our work revealed that GS has significant protective effects on SD, and metabolomics is a useful tool for evaluating efficacy and elucidating mechanism in TCM.

Preventive effect of total glycosides from Ligustri Lucidi Fructus against nonalcoholic fatty liver in mice

2015 ◽  
Vol 70 (9-10) ◽  
pp. 237-241 ◽  
Author(s):  
Nianyun Yang ◽  
Yiwen Zhang ◽  
Jianming Guo
Keyword(s):  
Fatty Liver ◽  
High Fat Diet ◽  
Inflammatory Responses ◽  
Regulatory Element ◽  
Lipid Synthesis ◽  
Protective Effects ◽  
Model Group ◽  
High Fat ◽  
Nonalcoholic Fatty Liver ◽  
Element Binding Protein

Abstract The protective effects of the total glycosides from Ligustri Lucidi Fructus against nonalcoholic fatty liver (NAFL) in mice were investigated. Liver injury was induced by the administration of high fat diet for 60 days. During this period, the model group received high fat diet only; the treatment groups received various drugs plus high fat diet. Compared with the model group, the total glycosides significantly decreased the contents of triglyceride (TG) and cholesterol (TC), as well as the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the serum. Moreover, the contents of TG and TC in liver tissue and the liver index were reduced. Histological findings also confirmed antisteatosis. Compared with the model group, total glycosides significantly reduced the levels of the sterol regulatory element binding protein-1c (SREBP-1c) and liver X receptor-a (LXR-α) protein, and down-regulated the expression of SREBP-1c, LXR-α and interleukin-6 (IL-6) mRNA in the liver. These results suggest that the total glycosides are effective in the treatment of NAFL of mice. Their mode of action is associated with inhibiting SREBP-1c, LXR-α and IL-6 mRNA, reducing lipid synthesis factor SREBP-1c and LXR-α protein and gene expression, suppressing inflammatory responses, then decreasing serum lipid and hepatic lipid.

Sign in / Sign up

Export Citation Format

Share Document