scholarly journals Combined Transcriptomic and Lipidomic Analysis Reveals Dysregulated Genes Expression and Lipid Metabolism Profiles in the Early Stage of Fatty Liver Disease in Rats

2021 ◽  
Vol 8 ◽  
Author(s):  
Ruina Zhai ◽  
Lei Feng ◽  
Yu Zhang ◽  
Wei Liu ◽  
Shengli Li ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Cholesterol Metabolism ◽  
Early Stage ◽  
Joint Analysis ◽  
Acid Uptake ◽  
Alcoholic Fatty Liver ◽  
Lipidomic Analysis ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease develops from simple steatosis to non-alcoholic steatohepatitis (NASH), which then potentially develops into liver cirrhosis. It is a serious threat to human health. Therefore, investigating the formation and development mechanism of non-alcoholic fatty liver disease (NAFLD) is of great significance. Herein, an early model of NAFLD was successfully established by feeding rats with a high-fat and choline-deficient diet. Liver tissue samples were obtained from rats in the fatty liver model group (NAFL) and normal diet control group (CON). Afterward, transcriptome and lipidomic analysis was performed. Transcriptome results revealed that 178 differentially expressed genes were detected in NAFL and CON groups. Out of which, 105 genes were up-regulated, 73 genes were downregulated, and 8 pathways were significantly enriched. A total of 982 metabolites were detected in lipidomic analysis. Out of which 474 metabolites were significantly different, 273 were up-regulated, 201 were downregulated, and 7 pathways were significantly enriched. Based on the joint analysis, 3 common enrichment pathways were found, including cholesterol metabolism and fat digestion and absorption metabolic pathways. Overall, in the early stage of NAFLD, a small number of genetic changes caused a strong response to lipid components. The strongest reflection was glycerides and glycerophospholipids. A significant increase in fatty acid uptake accompanied by cholesterol metabolism is the most prominent metabolic feature of the liver in the early stage of NAFLD. In the early stage of fatty liver, the liver had shown the characteristics of NASH.

scholarly journals miR-21 regulates triglyceride and cholesterol metabolism in non-alcoholic fatty liver disease by targeting HMGCR

2015 ◽  
Vol 35 (3) ◽  
pp. 847-853 ◽  
Author(s):  
CHUANZHENG SUN ◽  
FEIZHOU HUANG ◽  
XUNYANG LIU ◽  
XUEFEI XIAO ◽  
MINGSHI YANG ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Cholesterol Metabolism ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

scholarly journals S1101 Non-Alcoholic Fatty Liver Disease: Is the FIB-4 Score Still Useful in Detecting Early-Stage Liver Fibrosis?

2021 ◽  
Vol 116 (1) ◽  
pp. S519-S520
Author(s):  
Shilpa Junna ◽  
Malini Chauhan ◽  
Michael Bonelli ◽  
Zachary Warner ◽  
Mark Borgstrom ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Fibrosis ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Early Stage ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

scholarly journals Serum miR-379 expression is related to the development and progression of hypercholesterolemia in non-alcoholic fatty liver disease

2019 ◽  
Author(s):  
Kinya Okamoto ◽  
Masahiko Koda ◽  
Toshiaki Okamoto ◽  
Takumi Onoyama ◽  
Kenichi Miyoshi ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Internal Control ◽  
Fatty Liver Disease ◽  
Early Stage ◽  
Future Research ◽  
Mirna Cluster ◽  
Alcoholic Fatty Liver ◽  
Cholesterol Levels ◽  
Alcoholic Fatty Liver Disease

AbstractIntroductionNon-alcoholic fatty liver disease (NAFLD) has a wide spectrum, eventually leading to cirrhosis and hepatic carcinogenesis. We previously reported that a series of microRNAs (miRNAs) mapped in the 14q32.2 maternally imprinted gene region (Dlk1-Dio3 mat) are related to NAFLD development and progression in a mouse model. We examined the suitability of miR-379, a circulating Dlk1-Dio3 mat miRNA, as a human NAFLD biomarker.MethodsEighty NAFLD patients were recruited for this study. miR-379 was selected from the putative Dlk1-Dio3 mat miRNA cluster because it exhibited the greatest expression difference between NAFLD and non-alcoholic steatohepatitis in our preliminary study. Real-time PCR was used to examine the expression levels of miR-379 and miR-16 as an internal control.ResultsCompared to normal controls, serum miR-379 expression was significantly up-regulated in NAFLD patients. Receiver operating characteristic curve analysis suggested that miR-379 is a suitable marker for discriminating NAFLD patients from controls, with an area under the curve value of 0.72. Serum miR-379 exhibited positive correlations with alkaline phosphatase, total cholesterol, and low-density-lipoprotein cholesterol levels in patients with early stage NAFLD (Brunt fibrosis stage 0 to 1). The correlation between serum miR-379 and cholesterol levels was lost in early stage NAFLD patients treated with statins. Software-based predictions indicated that various energy metabolism–related genes, including insulin-like growth factor-1 (IGF-1) and IGF-1 receptor, are potential targets of miR-379.ConclusionsSerum miR-379 exhibits high potential as a biomarker for NAFLD. miR-379 appears to increase cholesterol lipotoxicity, leading to the development and progression of NAFLD, via interference with the expression of target genes, including those related to the IGF-1 signaling pathway. Our results could facilitate future research into the pathogenesis, diagnosis, and treatment of NAFLD.

FRI-335-Lect2, a new hepatokine regulating cholesterol metabolism in liver during non-alcoholic fatty liver disease

2019 ◽  
Vol 70 (1) ◽  
pp. e543
Author(s):  
Sandrine Pham ◽  
Mathilde Cadoux ◽  
Fadila Rayah ◽  
Stéphanie Bonnafous ◽  
Nesrine Mabrouk ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Cholesterol Metabolism ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

7088 A lipidomic analysis of non-alcoholic fatty liver disease (NAFLD)

2006 ◽  
Vol 44 ◽  
pp. S260-S261 ◽  
Author(s):  
P. Puri ◽  
R.A. Baillie ◽  
M. Wiest ◽  
F. Mirshahi ◽  
A.J. Sanyal
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Lipidomic Analysis ◽  
Alcoholic Fatty Liver Disease

scholarly journals Association of the SH2B1 rs7359397 Gene Polymorphism with Steatosis Severity in Subjects with Obesity and Non-Alcoholic Fatty Liver Disease

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1260 ◽  
Author(s):  
Nuria Perez-Diaz-del-Campo ◽  
Itziar Abete ◽  
Irene Cantero ◽  
Bertha Araceli Marin-Alejandre ◽  
J. Ignacio Monreal ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Regression Models ◽  
Risk Allele ◽  
Alcoholic Fatty Liver ◽  
Logistic Regression Models ◽  
Lipidomic Analysis ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver disease worldwide. Some genetic variants might be involved in the progression of this disease. The study hypothesized that individuals with the rs7359397 T allele have a higher risk of developing severe stages of NAFLD compared with non-carriers where dietary intake according to genotypes could have a key role on the pathogenesis of the disease. SH2B1 genetic variant was genotyped in 110 overweight/obese subjects with NAFLD. Imaging techniques, lipidomic analysis and blood liver biomarkers were performed. Body composition, general biochemical and dietary variables were also determined. The SH2B1 risk genotype was associated with higher HOMA-IR p = 0.001; and Fatty Liver Index (FLI) p = 0.032. Higher protein consumption (p = 0.028), less mono-unsaturated fatty acid and fiber intake (p = 0.045 and p = 0.049, respectively), was also referred to in risk allele genotype. Lipidomic analysis showed that T allele carriers presented a higher frequency of non-alcoholic steatohepatitis (NASH) (69.1% vs. 44.4%; p = 0.006). In the genotype risk group, adjusted logistic regression models indicated a higher risk of developing an advanced stage of NAFLD measured by FLI (OR 2.91) and ultrasonography (OR 4.15). Multinomial logistic regression models showed that risk allele carriers had higher liver fat accumulation risk (RRR 3.93) and an increased risk of NASH (RRR 7.88). Consequently, subjects carrying the T allele were associated with a higher risk of developing a severe stage of NAFLD. These results support the importance of considering genetic predisposition in combination with a healthy dietary pattern in the personalized evaluation and management of NAFLD.

scholarly journals Sodium fluorocitrate having inhibitory effect on fatty acid uptake ameliorates high fat diet-induced non-alcoholic fatty liver disease in C57BL/6J mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Seung A. Hong ◽  
Ik-Rak Jung ◽  
Sung-E. Choi ◽  
Yoonjung Hwang ◽  
Soo-Jin Lee ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Liver Disease ◽  
Fatty Liver ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
Fatty Acid Uptake ◽  
Acid Uptake ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

AbstractNon-alcoholic fatty liver disease (NAFLD) is excessive fat build-up in the liver without alcohol consumption and includes hepatic inflammation and damage. Excessive influx of fatty acids to liver from circulation is thought to be a pathogenic cause for the development of NAFLD. Thus, inhibition of fatty acid intake into hepatocyte would be a maneuver for protection from high fat diet (HFD)-induced NAFLD. This study was initiated to determine whether sodium fluorocitrate (SFC) as a fatty acid uptake inhibitor could prevent palmitate-induced lipotoxicity in hepatocytes and protect the mice from HFD-induced NAFLD. SFC significantly inhibited the cellular uptake of palmitate in HepG2 hepatocytes, and thus prevented palmitate-induced fat accumulation and death in these cells. Single treatment with SFC reduced fasting-induced hepatic steatosis in C57BL/6J mice. Concurrent treatment with SFC for 15 weeks in HFD-fed C57BL/6J mice prevented HFD-induced fat accumulation and stress/inflammatory signal activation in the liver. SFC restored HFD-induced increased levels of serum alanine aminotransferase and aspartate aminotransferases as hepatic injury markers in these mice. SFC treatment also improved HFD-induced hepatic insulin resistance, and thus ameliorated HFD-induced hyperglycemia. In conclusion, inhibition of fatty acid mobilization into liver through SFC treatment can be a strategy to protect from HFD-induced NAFLD.

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