scholarly journals Metabolic analysis of early nonalcoholic fatty liver disease in humans using liquid chromatography-mass spectrometry

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Cheng Hu ◽  
Tao Wang ◽  
Xiaoyu Zhuang ◽  
Qiaoli Sun ◽  
Xiaochun Wang ◽  
...  

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.

2020 ◽  
Author(s):  
Cheng Hu ◽  
Tao Wang ◽  
Jiaqi Zhang ◽  
Yuanye Jiang ◽  
Qin Cao

Abstract BackgroundNAFLD is a common metabolic disorders disease which influenced 20~30% people. NAFLD can progress to cirrhosis, liver fibrosis and even liver cancer. Liver puncture is the gold standard. However, due to its trauma and possible complications, its clinical use is currently limited. Therefore, it is of great clinical significance and value to find a noninvasive biochemical index that can diagnose NAFLD early.ObjectiveOur aim was to identify the potential biomarkers in NAFLD people in early stage via untargeted metabolomics study.MethodsIn our research, From January to October 2019, 224 patients aged 18-55 were selected from the outpatient department and ward of gastroenterology department of Putuo Hospital in Shanghai.According to the NAFLD diagnostic criteria of the guidelines for diagnosis and treatment of nonalcoholic fatty liver disease (2018) formulated by the National workship on Fatty liver and alcoholic liver disease and Chinese Society on Hepatology, they were divided into the healthy control group and the experimental group.Besides,on the same day, the height, weight, waist, BMI, blood pressure and heart rate of patients were measured, and fasting blood was taken to obtain blood glucose,ALT, AST, TB, DB, TP, ALB, Che, ALP, γ - GT, TG, TC, HDL-C, LDL-C and other serum data.Serum samples were analyzed using LC/MS and data was processed by SIEVE software and simca-P to validate the potential biomarkers. The altered metabolites were identified by variable importance in projection value (VIP > 1) and ANOVA (p<0.01). The pathway analysis was performed by using MetaboAnalyst 4.0. In addition, our project has passed the review of ethics committee of Putuo Hospital Affiliated to Shanghai University of traditional Chinese medicine, and its ethics approval number is ptec-a-2018-49-1.ResultsThe serum biochemical indicators of early NAFLD patients showed no significant difference with NC (p>0.05). While there was significant difference of blood lipids indicators between NAFLD and NC (p<0.001). Finally, 55 metabolites were identified and the AUC of ROC curve results showed that new identified biomarkers owned high predictability and reliability. ConclusionIt is found that 15 metabolites in serum were of great diagnostic value in early NAFLD patients. AUC of these biomarkers (>0.9) were much higher than clinical indicators (0.770). This may be worth further research in the clinic.


2019 ◽  
Vol 8 (4) ◽  
pp. 299-308 ◽  
Author(s):  
Jia Li ◽  
Yan Zhao ◽  
Caoxin Huang ◽  
Zheng Chen ◽  
Xiulin Shi ◽  
...  

Objective Exercise benefits people with nonalcoholic fatty liver disease (NAFLD). The aim of this study was to identify a panel of biomarkers and to provide the possible mechanism for the effect of exercise on NAFLD patients via an untargeted mass spectrometry-based serum metabolomics study. Methods NAFLD patients were classified randomly into a control group (n = 74) and a 6-month vigorous exercise (n = 68) group. Differences in serum metabolic profiles were analyzed using untargeted ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) technology. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to validate the differences between these two groups, and altered metabolites were obtained by ANOVA (fold change >2, P < 0.05) and identified with the online database Metlin and an in-house database. Results Metabolic profiling and multiple statistical analyses of the serum samples indicated significant differences between the NAFLD patients in the control and the 6-month vigorous exercise groups. Finally, 36 metabolites were identified between the control vs exercise groups. These metabolites were mainly associated with glycerophospholipid- and sphingolipid-related pathways. Conclusion Our study demonstrates that glycerophospholipid and sphingolipid alterations may contribute to the mechanism underlying the effect of exercise on NAFLD patients. A LC-MS-based metabolomics approach has a potential value for screening exercise-induced biomarkers.


Author(s):  
U. O. Mudra

Background. Gout is still one of the major health problems despite significant advances in treatment in recent years. It has been proved that pathogenetic mechanisms of development and progression of gout are associated with nonalcoholic fatty liver disease. Complex pathogenic treatment of patients aimed at different parts of the pathological process has recently been supplemented with the enterosorbents. Objective. The aim of the research is to study the clinical features of gout with concomitant nonalcoholic fatty liver disease (NAFLD) and to evaluate the effect of carbon enterosorbent on its course. Methods. 123 patients were involved in the study. They were divided into 2 groups: group 1 included patients with gout without liver damage, and group 2 included patients with concomitant NAFLD. Each of these groups was divided into subgroups, in which the patients received carbon enterosorbent carboline plus basic treatment. The control group consisted of 30 healthy persons. Anamnesis, physical examination, uric acid (UA), C-reactive protein (CRP) content, erythrocyte sedimentation rate (ESR) in serum were determined. Gout activity was evaluated using the Gout Activity Score (GAS). Results. Basic treatment in combination with carbon enterosorbent contributed to faster cure of intoxication, pain and joint syndromes, as well as decrease of the inflammatory process activity. Conclusions. The course of gout in the patients with concomitant NAFLD is more severe. Adding of carbon granular enterosorbent carboline in the complex treatment of patients with gout with or without concomitant NAFLD in the exacerbation phase contributes to a faster cureing dynamics of clinical and laboratory manifestations of the disease.


2020 ◽  
Vol 106 (1) ◽  
pp. e34-e44
Author(s):  
Aya Bardugo ◽  
Cole D Bendor ◽  
Inbar Zucker ◽  
Miri Lutski ◽  
Tali Cukierman-Yaffe ◽  
...  

Abstract Context The long-term risk of type 2 diabetes in adolescents with nonalcoholic fatty liver disease (NAFLD) is unclear. Objective To assess type 2 diabetes risk among adolescents with NAFLD. Design and Setting A nationwide, population-based study of Israeli adolescents who were examined before military service during 1997–2011 and were followed until December 31, 2016. Participants A total of 1 025 796 normoglycemic adolescents were included. Interventions Biopsy or radiographic tests were prerequisite for NAFLD diagnosis. Data were linked to the Israeli National Diabetes Registry. Main Outcome Measures Type 2 diabetes incidence. Results During a mean follow-up of 13.3 years, 12 of 633 adolescents with NAFLD (1.9%; all with high body mass index [BMI] at baseline) were diagnosed with type 2 diabetes compared with 2917 (0.3%) adolescents without NAFLD. The hazard ratio (HR) for type 2 diabetes was 2.59 (95% confidence interval [CI], 1.47–4.58) for the NAFLD vs. the non-NAFLD group after adjustment for BMI and sociodemographic confounders. The elevated risk persisted in several sensitivity analyses. These included an analysis of persons without other metabolic comorbidities (adjusted HR, 2.75 [95% CI, 1.48-5.14]) and of persons with high BMI; and an analysis whose outcome was type 2 diabetes by age 30 years (adjusted HR, 2.14 [95% CI, 1.02-4.52]). The results remained significant when a sex-, birth year-, and BMI-matched control group was the reference (adjusted HR, 2.98 [95% CI, 1.54-5.74]). Conclusions Among normoglycemic adolescents, NAFLD was associated with an increased adjusted risk for type 2 diabetes, which may be apparent before age 30 years.


Medicina ◽  
2019 ◽  
Vol 55 (9) ◽  
pp. 600 ◽  
Author(s):  
Oral ◽  
Sahin ◽  
Turker ◽  
Kocak

Background and objectives: Nonalcoholic fatty liver disease (NAFLD) is associated with multiple factors such as hypertension, diabetes, dyslipidemia, obesity, and hyperuricemia. We aim to investigate the relationship between uric acid and NAFLD in a non-obese and young population. Materials and Methods: This study was performed in January 2010–2019 with a group of 367 (225 patients in the NAFLD group and 142 in the control group) patients with liver biopsy-proven NAFLD or no NAFLD. Patients with NAFLD were classified according to the percentage of steatosis as follows, group I had 1–20% and group II >20%. Demographic, clinical, and laboratory (biochemical parameters) features were collected retrospectively. Results: The mean body mass index (BMI) and age of the patients were 26.41 ± 3.42 and 32.27 ± 8.85, respectively. The BMI, homeostatic model of assessment (HOMA-IR), and uric acid (UA) values of the NAFLD group were found to be significantly higher than those of the controls. A positive correlation was found between the NAFLD stage and UA. The following factors were independently associated with NAFLD: BMI, HOMA-IR, and UA. In addition, the cut-off value of UA was 4.75 mg/dl with a sensitivity of 45.8% and a specificity of 80.3%. Conclusions: UA is a simple, non-invasive, cheap, and useful marker that may be used to predict steatosis in patients with NAFLD.


2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Ning Shao ◽  
Xin-Yang Yu ◽  
Xue-Fei Ma ◽  
Wen-Jian Lin ◽  
Ming Hao ◽  
...  

Objective. This study is aimed at investigating whether exenatide (Exe) delays the progression of nonalcoholic fatty liver disease (NAFLD) in C57BL/6 mice by targeting the NLRP3 inflammasome through the autophagy/mitophagy pathway. Methods. Thirty male C57BL/6 mice were randomly divided into three groups: control group (n=10), model group (n=10), and Exe (exenatide) group (n=10). Mouse models of NAFLD and diabetes were established using a high-fat diet and streptozocin. Results. The levels of fasting blood glucose (FBG), total cholesterol (TC), and triglyceride (TG) in the serum were significantly reduced after Exe treatment. The body weight, liver weight/body weight, and number of lipid droplets in the liver significantly decreased in Exe-treated mice. Treatment with Exe markedly reduced the levels of liver lipids, malondialdehyde (MDA), and alanine aminotransferase (ALT) in serum and livers. The number of autophagosomes increased significantly in the Exe group. The expression of LC3A/B-II/I, Beclin-1, Parkin, and BNIP3L increased significantly, whereas NLRP3 and IL-1β proteins were suppressed after Exe treatment. Conclusion. We successfully established a mouse model of NAFLD and diabetes. Exe may reduce oxidative stress injury and inhibit the NLRP3 inflammasome by enhancing the autophagy/mitophagy pathway in liver, which has a protective effect on the liver in NAFLD and diabetes in C57BL/6 mice.


Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3455
Author(s):  
Jia Han ◽  
Xin Guo ◽  
Tomoyuki Koyama ◽  
Daichi Kawai ◽  
Jing Zhang ◽  
...  

Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases with no approved treatment. Zonarol, an extract from brown algae, has been proven to have anti-inflammatory and antioxidant effects. In this study, we investigated the role of zonarol in the progression of methionine- and choline-deficiency (MCD) diet-induced NAFLD in mice. After oral treatment with zonarol, a lighter body weight was observed in zonarol group (ZG) mice in comparison to control group (CG) mice. The NAFLD scores of ZG mice were lower than those of CG mice. Hepatic and serum lipid levels were also lower in ZG mice with the reduced expression of lipid metabolism-related factors. Furthermore, ZG mice showed less lipid deposition, less inflammatory cell infiltration and lower inflammatory cytokine levels in comparison to CG mice. Moreover, the numbers of 8-hydroxy-20-deoxyguanosine (8-OHdG)-positive hepatocytes and levels of hepatic and serum thiobarbituric acid reactive substances (TBARS) were significantly lower in comparison to CG mice. The expression levels of nuclear factor erythroid 2 related factor 2 (Nrf2), as well as its upstream and downstream molecules, changed in ZG mice. Zonarol could prevent the progression of NAFLD by decreasing inflammatory responses, oxidative stress and improving lipid metabolism. Meanwhile the Nrf2 pathway may play an important role in these effects


2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Cosmas Rinaldi A. Lesmana ◽  
Levina S. Pakasi ◽  
Aru W. Sudoyo ◽  
Ening Krisnuhoni ◽  
Laurentius A. Lesmana

Aim. Nonalcoholic fatty liver disease (NAFLD) has been known as a risk for the presence of colon polyp and CRC development. This study was aimed to find out the clinical significance of colon polyps’ pathology among NAFLD patients. Method. A retrospective database study was done in patients who underwent elective colonoscopy within one-year period in a referral private hospital, Jakarta. Subjects were adult patients who also had documented abdominal ultrasound (US). The association between NAFLD and colonic polyp was analyzed using Chi-square test with odds ratio (OR) and its corresponding 95% confidence interval (CI). Results. A total of 138 adult patients were enrolled; 68 (51.1%) were men. Patients’ mean age was 56.8 ± 15.3 years old. Colon polyps were found in 49 (35.5%) cases; the most common histopathology was adenoma (42.9%). NAFLD was found in 68 (49.3%) of patients. Colon polyps were found to be more among patients with NAFLD than in those without NAFLD (44.1% vs. 27.1%; OR: 2.119; 95% CI: 1.040–4.318). Colon polyps were found in 30 (44.1%) NAFLD patients, where 18 (26.5%) patients had adenomatous polyp, and from this subset of patients with adenomatous polyp, 6 (8.8%) patients had mild dysplasia, 8 (11.8%) had moderate dysplasia, 1 (1.5%) had severe dysplasia, and 3 (4.4%) had adenocarcinoma. Conclusions. NAFLD is associated with increased risk of any colon polyp, regardless of the histopathological type, compared with patients without NAFLD. This finding implies the necessity to perform screening colonoscopy in patients with NAFLD in the future.


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