Liquid Chromatography−Mass Spectrometry-Based Parallel Metabolic Profiling of Human and Mouse Model Serum Reveals Putative Biomarkers Associated with the Progression of Nonalcoholic Fatty Liver Disease

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is a common metabolic disease that affects 20–30% of individuals worldwide. Liver puncture remains the gold standard for the diagnosis of liver diseases despite limitations regarding invasive nature and sample variability. It is of great clinical significance to find noninvasive biomarkers to detect and predict NAFLD. Objective The aims of this study were to identify potential serum markers in individuals with early-stage NAFLD and to advance the mechanistic understanding of this disease using a high-throughput mass spectrometry-based untargeted metabolomics approach. Methods One hundred and twelve patients with early-stage NAFLD aged 18–55 were recruited according to the guidelines. The control group included 112 healthy participants. The demographic, anthropometric, clinical and laboratory data of all participants were systematically collected. Serum samples were obtained after an overnight fast. The comprehensive serum metabolomic analysis was performed by ultra-performance liquid chromatography-Orbitrap mass spectrometry. The resultant data was processed by Compound Discover and SIMCA-P software to validate the potential biomarkers. Significantly altered metabolites were evaluated by variable importance in projection value (VIP > 1) and ANOVA (p < 0.01). Pathway analysis was performed using MetaboAnalyst 4.0. Results The liver function test of early NAFLD patients showed no statistical differences to control group (p > 0.05). However, obvious differences in blood lipids were observed between subjects with NAFLD and controls (p < 0.001). In total, 55 metabolites showed significant changes in experimental group were identified. The area under curve (AUC) values deduced by receiver operating curve (ROC) analysis indicated that these newly identified biomarkers have high predictability and reliability. Of these, 15 metabolites with AUC greater than 0.9 were of great diagnostic value in early NAFLD patients. Conclusion In this study, a total of 15 serum metabolites were found to strongly associate with early NAFLD. These biomarkers may have great clinical significance in the early diagnosis of NAFLD, as well as to follow response to therapeutic interventions.

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Analysis of Therapeutic Effect ofIlex hainanensisMerr. Extract on Nonalcoholic Fatty Liver Disease through Urine Metabolite Profiling by Ultraperformance Liquid Chromatography/Quadrupole Time of Flight Mass Spectrometry

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/451975 ◽

2013 ◽

Vol 2013 ◽

pp. 1-12 ◽

Cited By ~ 5

Author(s):

Jing-jing Li ◽

Jie Yang ◽

Wei-xi Cui ◽

Xiao-qing Chen ◽

Gang-ling Chen ◽

...

Keyword(s):

Mass Spectrometry ◽

Liquid Chromatography ◽

Liver Disease ◽

Fatty Liver ◽

High Fat Diet ◽

Fatty Liver Disease ◽

Therapeutic Effects ◽

High Fat ◽

Nonalcoholic Fatty Liver ◽

Flight Mass Spectrometry

Nonalcoholic fatty liver disease (NAFLD), the most common form of chronic liver disease, is increased worldwide in parallel with the obesity epidemic. Our previous studies have showed that the extract ofI. hainanensis(EIH) can prevent NAFLD in rat fed with high-fat diet. In this work, we aimed to find biomarkers of NAFLD and investigate the therapeutic effects of EIH. NAFLD model was induced in male Sprague-Dawley rats by high-fat diet. The NAFLD rats were administered EIH orally (250 mg/kg) for two weeks. After the experimental period, samples of 24 h urine were collected and analyzed by ultraperformance liquid chromatography/quadrupole time of flight mass spectrometry (UPLC-Q-TOF). Orthogonal partial least squares analysis (OPLSs) models were built to find biomarkers of NAFLD and investigate the therapeutic effects of EIH. 22 metabolites, which are distributed in several metabolic pathways, were identified as potential biomarkers of NAFLD. Taking these biomarkers as screening indexes, EIH could reverse the pathological process of NAFLD through regulating the disturbed pathway of metabolism. The metabolomic results not only supply a systematic view of the development and progression of NAFLD but also provide a theoretical basis for the prevention or treatment of NAFLD.

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652 Iron Excess Leads to Upregulation of NLRP3 Inflammasome, TLRS and NF-kB-Dependent Proinflammatory Activation in Primary Murine Dendritic Cells and in a Mouse Model of Nonalcoholic Fatty Liver Disease

Gastroenterology ◽

10.1016/s0016-5085(16)33524-7 ◽

2016 ◽

Vol 150 (4) ◽

pp. S1043

Author(s):

Priya Handa ◽

Vicki Morgan-Stevenson ◽

Kris V. Kowdley

Keyword(s):

Dendritic Cells ◽

Liver Disease ◽

Mouse Model ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Nlrp3 Inflammasome ◽

Fatty Liver Disease ◽

Nonalcoholic Fatty Liver

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An albino mouse model of nonalcoholic fatty liver disease induced using high-fat liquid “Lieber-DeCarli” diet: a preliminary investigation

Porto Biomedical Journal ◽

10.1097/j.pbj.0000000000000071 ◽

2020 ◽

Vol 5 (4) ◽

pp. e071

Author(s):

Ayokanmi Ore ◽

Regina Ngozi Ugbaja ◽

Abideen Idowu Adeogun ◽

Oluseyi Adeboye Akinloye

Keyword(s):

Liver Disease ◽

Mouse Model ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Fatty Liver Disease ◽

Preliminary Investigation ◽

High Fat ◽

Nonalcoholic Fatty Liver

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Ethyl Acetate Fraction of Amomum xanthioides Ameliorates Nonalcoholic Fatty Liver Disease in a High-Fat Diet Mouse Model

Nutrients ◽

10.3390/nu12082433 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2433

Author(s):

Hwi-Jin Im ◽

Seung-Ju Hwang ◽

Jin-Seok Lee ◽

Sung-Bae Lee ◽

Ji-Yun Kang ◽

...

Keyword(s):

Liver Disease ◽

Mouse Model ◽

Fatty Liver ◽

Ethyl Acetate ◽

Nonalcoholic Fatty Liver Disease ◽

High Fat Diet ◽

Fatty Liver Disease ◽

Ethyl Acetate Fraction ◽

High Fat ◽

Nonalcoholic Fatty Liver

The global prevalence of nonalcoholic fatty liver disease (NAFLD) is estimated to be 25% and has continued to increase; however, no drugs have yet been approved for NAFLD treatments. The ethyl acetate fraction of Amomum xanthioides (EFAX) was previously reported to have an anti-hepatic fibrosis effect, but its effects on steatosis or steatohepatitis remain unclear. This study investigated the anti-fatty liver of EFAX using a high-fat diet mouse model. High-fat diet intake for 8 weeks induced hepatic steatosis with mild inflammation and oxidative damage and increased the adipose tissue weight along with the development of dyslipidemia. EFAX treatment significantly ameliorated the steatohepatic changes, the increased weight of adipose tissues, and the altered serum lipid profiles. These observed effects were possibly due to the lipolysis-dominant activity of EFAX on multiple hepatic proteins including sterol regulatory element-binding protein (mSREBP)-1c, peroxisome proliferator-activated receptor (PPAR)-α, AMP-activated protein kinase, and diglyceride acyltransferases (DGATs). Taken together, these results show that EFAX might be a potential therapeutic agent for regulating a wide spectrum of NAFLDs from steatosis to fibrosis via multiple actions on lipid metabolism-related proteins. Further studies investigating clear mechanisms and their active compounds are needed.

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