scholarly journals Comprehensive Analysis of the Expression Profiles of Hepatic lncRNAs in the Mouse Model of Alcoholic Liver Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaobing Dou ◽  
Wenwen Yang ◽  
Qinchao Ding ◽  
Qiang Han ◽  
Qianyu Qian ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Liver Disease ◽  
Mouse Model ◽  
Alcoholic Liver Disease ◽  
Expression Profiles ◽  
Triglyceride Accumulation ◽  
Genes Encoding ◽  
Pathway Analyses

Background and Aim: The worldwide prevalence of alcoholic liver disease (ALD) due to escalating alcohol consumption has presented an unprecedented pressure on human health. A few studies have determined long non-coding RNAs (lncRNAs) involved in the pathogenesis of liver diseases. However, the roles of lncRNAs in ALD development is still poorly understood.Methods: An ALD mouse model was established and confirmed. Expression profiles of lncRNAs were obtained by whole transcriptome sequencing. The altered lncRNAs in ALD mice were further verified by qRT-PCR. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to enrich the functions of these lncRNAs. In combination with miRNA and mRNA profiles, we constructed concise endogenous RNA (ceRNA) networks. The function of the most up/downregulated lnRNA was further verified and investigated in both ALD model and AML-12 cells.Results: Totally, five downregulated lncRNAs were obtained and verified in ALD mice. The GO term and KEGG pathway analyses revealed that the identified lncRNAs were associated with alcohol-induced hepatic oxidative damage, cellular inflammation, and lipid metabolism. Combination the differentially modulated miRNAs and mRNAs with ceRNA network analysis, we constructed five ceRNA networks and obtained 30 miRNAs and 25 mRNAs that may participate in ALD. Further, we verified and investigate the function of the most downregulated lnc_1700023H06Rik. Depletion lnc_1700023H06Rik reduced genes encoding for lipid metabolism, especially mRNA Acat2 (ENSMUST00000159697) and Pgrmc2 (ENSMUST00000058578) both in vivo and in vitro. Knocking down lnc_1700023H06Rik induced triglyceride accumulation and lactate dehydrogenase leakage in AML12 cells, consisting with that in alcohol-treated cells.Conclusion: The five remarkably downregulated lncRNAs in ALD mouse model were identified as novel biomarkers, highlighting the key role of lncRNAs in the development of ALD. The effect of lnc_1700023H06Rik plays a pivotal role in lipid deposition and its pathological pathway in ALD needs further investigation.

scholarly journals Liraglutide Attenuates Nonalcoholic Fatty Liver Disease through Adjusting Lipid Metabolism via SHP1/AMPK Signaling Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Peng Yu ◽  
Xi Xu ◽  
Jing Zhang ◽  
Xuan Xia ◽  
Fen Xu ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Hepg2 Cells ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver ◽  
Ampk Signaling

A glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide (LR) had been experimentally and clinically shown to ameliorate nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate the beneficial effect of LR on NAFLD in vivo and in vitro and its underlying molecular mechanism. The effects of LR were examined on the high-fat diet-induced in vivo model in mice and in vitro model of NAFLD in human HepG2 cells. Liver tissues and HepG2 cells were procured for measuring lipid metabolism, histological examination, and western blot analysis. LR administration significantly lowered the serum lipid profile and lipid disposition in vitro and in vivo because of the altered expression of enzymes on hepatic gluconeogenesis and lipid metabolism. Moreover, LR significantly decreased Src homology region 2 domain-containing phosphatase-1 (SHP1) and then increased the expression of phosphorylated-AMP-activated protein kinase (p-AMPK). However, the overexpression of SHP1 mediated by lentivirus vector reversed LR-induced improvement in lipid deposition. Moreover, SHP1 silencing could further increase the expression of p-AMPK to ameliorate lipid metabolism and relative lipogenic gene induced by LR. In addition, abrogation of AMPK by Compound C eliminated the protective effects of LR on lipid metabolism without changing the expression of SHP1. LR markedly prevented NAFLD through adjusting lipid metabolism via SHP1/AMPK signaling pathway.

scholarly journals Expression of genes encoding mitochondrial proteins can distinguish nonalcoholic steatosis from steatohepatitis.

2007 ◽  
Vol 54 (2) ◽  
pp. 341-348 ◽  
Author(s):  
Piotr Bragoszewski ◽  
Andrzej Habior ◽  
Bozena Walewska-Zielecka ◽  
Jerzy Ostrowski
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Expression Profiles ◽  
Liver Steatosis ◽  
Mitochondrial Proteins ◽  
Morphological Examination ◽  
Nonalcoholic Fatty Liver ◽  
Triglyceride Accumulation ◽  
Genes Encoding

In patients without substantial alcohol use, triglyceride accumulation in the liver can lead to nonalcoholic fatty liver disease (NAFLD) that may progress to nonalcoholic steatohepatitis (NASH). The differential diagnosis between NAFLD and NASH can be accomplished only by morphological examination. Although the relationship between mitochondrial dysfunction and the progression of liver pathologic changes has been described, the exact mechanisms initiating primary liver steatosis and its progression to NASH are unknown. We selected 16 genes encoding mitochondrial proteins which expression was compared by quantitative RT-PCR in liver tissue samples taken from patients with NAFLD and NASH. We found that 6 of the 16 examined genes were differentially expressed in NAFLD versus NASH patients. The expression of hepatic HK1, UCP2, ME2, and ME3 appeared to be higher in NASH than in NAFLD patients, whereas HMGCS2 and hnRNPK expression was lower in NASH patients. Although the severity of liver morphological injury in the spectrum of NAFLD-NASH may be defined at the molecular level, expression of these selected 6 genes cannot be used as a molecular marker aiding histological examination. Moreover, it is still unclear whether these differences in hepatic gene expression profiles truly reflect the progression of morphological abnormalities or rather indicate various metabolic and hormonal states in patients with different degrees of fatty liver disease.

scholarly journals MicroRNA Signature in Alcoholic Liver Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Shashi Bala ◽  
Gyongyi Szabo
Keyword(s):  
Liver Disease ◽  
Alcoholic Liver Disease ◽  
Current Knowledge ◽  
Isolated Hepatocytes ◽  
Tnf Alpha ◽  
Insight Into ◽  
Global Health Problem

Alcoholic liver disease (ALD) is a major global health problem. Chronic alcohol use results in inflammation and fatty liver, and in some cases, it leads to fibrosis and cirrhosis or hepatocellular carcinoma. Increased proinflammatory cytokines, particularly TNF alpha, play a central role in the pathogenesis of ALD. TNF alpha is tightly regulated at transcriptional and posttranscriptional levels. Recently, microRNAs (miRNAs) have been shown to modulate gene functions. The role of miRNAs in ALD is getting attention, and recent studies suggest that alcohol modulates miRNAs. Recently, we showed that alcohol induces miR-155 expression both in vitro (RAW 264.7 macrophage) and in vivo (Kupffer cells, KCs of alcohol-fed mice). Induction of miR-155 contributed to increased TNF alpha production and to the sensitization of KCs to produce more TNF alpha in response to LPS. In this paper, we summarize the current knowledge of miRNAs in ALD and also report increased expression of miR-155 and miR-132 in the total liver as well as in isolated hepatocytes and KCs of alcohol-fed mice. Our novel finding of the alcohol-induced increase of miRNAs in hepatocytes and KCs after alcohol feeding provides further insight into the evolving knowledge regarding the role of miRNAs in ALD.

scholarly journals The In Vivo Transcriptomic Blueprint of Mycobacterium tuberculosis in the Lung

2021 ◽  
Vol 12 ◽  
Author(s):  
Mariateresa Coppola ◽  
Rachel P-J. Lai ◽  
Robert J. Wilkinson ◽  
Tom H. M. Ottenhoff
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Metabolic Pathways ◽  
Large Scale ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Genes Encoding ◽  
High Concordance ◽  
Lower Correlation

Mycobacterium tuberculosis (Mtb) genes encoding proteins targeted by vaccines and drugs should be expressed in the lung, the main organ affected by Mtb, for these to be effective. However, the pulmonary expression of most Mtb genes and their proteins remains poorly characterized. The aim of this study is to fill this knowledge gap. We analyzed large scale transcriptomic datasets from specimens of Mtb-infected humans, TB-hypersusceptible (C3H/FeJ) and TB-resistant (C57BL/6J) mice and compared data to in vitro cultured Mtb gene-expression profiles. Results revealed high concordance in the most abundantly in vivo expressed genes between pulmonary Mtb transcriptomes from different datasets and different species. As expected, this contrasted with a lower correlation found with the highest expressed Mtb genes from in vitro datasets. Among the most consistently and highly in vivo expressed genes, 35 have not yet been explored as targets for vaccination or treatment. More than half of these genes are involved in protein synthesis or metabolic pathways. This first lung-oriented multi-study analysis of the in vivo expressed Mtb-transcriptome provides essential data that considerably increase our understanding of pulmonary TB infection biology, and identifies novel molecules for target-based TB-vaccine and drug development.

scholarly journals Black Carrot (Daucus carota ssp. sativus var. Atrorubens Alef.) Extract Protects against Ethanol-induced Liver Injury via the Suppression of Phosphodiesterase 4 mRNA Expression

2021 ◽  
Vol 9 (2) ◽  
Author(s):  
Kitano A ◽  
◽  
Norikura T ◽  
Matsui-Yuasa I ◽  
Shimakawa H ◽  
...  
Keyword(s):  
Liver Disease ◽  
Alcoholic Liver Disease ◽  
Control Level ◽  
Intracellular Camp ◽  
Transcriptional Level ◽  
Protective Effects ◽  
Black Carrot ◽  
Camp Levels

We examined the protective effects of Black Carrot Extract (BCE) on Alcoholic Liver Disease (ALD) using in vivo and in vitro models. In an in vivo ethanol-Carbon Tetrachloride (CCl4)-treated rat model, BCE treatment suppressed serum alanine aminotransferase and aspartate aminotransferase activity. BCE also suppressed ethanol- and CCl4-induced alcoholic liver disease. Furthermore, we observed that the BCE or butanol-extracted fraction of BCE (BCE-BuOH) recovered the cell viability of in vitro ethanol-treated hepatocytes. BCE-BuOH also suppressed the production of reactive oxygen species induced by ethanol to the control level. Moreover, BCE-BuOH regulated the activities of three alcoholic metabolism-related enzymes: cytochrome P450 2E1 activity was suppressed at the posttranslational level, alcohol dehydrogenase activity was increased at the posttranslational level, and aldehyde dehydrogenase 2 activity was increased at the transcriptional level. Novel findings in this study include an increase in intracellular Cyclic Adenosine 3’,5’-Monophosphate (cAMP) levels in hepatocytes with the simultaneous addition of ethanol and BCE-BuOH and the suppression of changes in the activities of three enzymes upon treatment with an inhibitor of cAMP-dependent protein kinase. Our study also found that BCE-BuOH suppressed the expression of phosphodiesterase 4b mRNA, which increased intracellular cAMP levels. These results suggest that BCE is useful for the treatment of ALD.

1,25-Dihydroxyvitamin D3-induced alterations of lipid metabolism in human monocyte-macrophages

1989 ◽  
Vol 257 (2) ◽  
pp. E290-E295
Author(s):  
J. B. Roullet ◽  
M. Haluska ◽  
O. Morchoisne ◽  
D. A. McCarron
Keyword(s):  
Lipid Metabolism ◽  
Cholesteryl Ester ◽  
Human Monocyte ◽  
Dietary Vitamin ◽  
Triglyceride Synthesis ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3 ◽  
Triglyceride Accumulation

An in vivo atherogenic role of dietary vitamin D has been postulated. To address this hypothesis we sought to determine the in vitro effects of its active circulating metabolite, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on lipid metabolism in human monocyte-derived macrophages. When cultured 6 days in the presence of 10(-8) M 1,25(OH)2D3 monocyte-macrophages accumulated significantly more triglycerides than control cells: 987.6 +/- 26.8 vs. 779.3 +/- 24.1 micrograms/mg protein (P less than 0.001). Triglyceride accumulation was associated with a hormone-induced stimulation of triglyceride synthesis as determined by [3H]oleate incorporation into cellular triglycerides. The effect of the hormone was significant after 24 h and dose dependent [10(-11) to 10(-8) M 1,25(OH)2D3]. It was specific since 10(-7) M 25-hydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 did not stimulate triglyceride synthesis, and its magnitude decreased from 1 to 9 days of culture. 1,25(OH)2D3 (10(-8) M) modified the cholesteryl ester metabolism of monocyte-macrophages only in the presence of acetylated low-density lipoproteins (50 micrograms/ml); it induced a significant increase of cellular cholesteryl ester content (21.9 +/- 1.1 vs. 11.7 +/- 1.7 micrograms/mg protein; P less than 0.001) and of esterification rate of cholesterol measured by [3H]oleate incorporation into cellular cholesteryl esters (17.2 +/- 0.9 vs. 6.5 +/- 0.3 nmol.mg protein-1.24 h-1; P less than 0.001) by comparison with control cells. These results show that 1,25(OH)2D3 alters in vitro lipid metabolism in the human monocyte-macrophage and suggest a new in vivo role for the hormone.

Cryotolerance and global gene-expression patterns of Bos taurus indicus and Bos taurus taurus in vitro- and in vivo-produced blastocysts

2014 ◽  
Vol 26 (8) ◽  
pp. 1129 ◽  
Author(s):  
Mateus J. Sudano ◽  
Ester S. Caixeta ◽  
Daniela M. Paschoal ◽  
Alicio Martins ◽  
Rui Machado ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lipid Metabolism ◽  
Bos Taurus ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Global Gene Expression ◽  
Embryo Viability ◽  
Bos Taurus Indicus

In a 2 × 2 factorial experimental design, embryo development, cryotolerance and global gene expression of Nellore (Bos taurus indicus) and Simmental (Bos taurus taurus) blastocysts produced in vitro (IVP) and in vivo (multiple ovulation derived embryo, MODE) were assessed. Blastocyst production was higher in Nellore than in Simmental (47.7 ± 2.0% vs 27.0 ± 2.0%) cows. The total numbers of ova or embryos recovered (5.5 ± 0.9 vs 3.7 ± 0.8) and transferable embryos (3.8 ± 1.0 vs 2.3 ± 0.8) per cow were not different between breeds. Simmental and MODE (34.6% and 38.5%, n = 75 and 70) blastocysts had higher survival rates after cryopreservation compared with Nellore and IVP (20.2% and 18.1%, n = 89 and 94) embryos, respectively. Differences between transcriptomes were addressed by principal-component analysis, which indicated that gene expression was affected by subspecies (158 genes), origin (532 genes) and interaction between both subspecies and origin (53 genes). Several functional processes and pathways relevant to lipid metabolism and embryo viability involving differentially expressed genes were identified. The lipid metabolism-related genes were upregulated in Simmental (AUH and ELOVL6) and IVP (ACSL3 and ACSL6) blastocysts. The expression profiles of genes related to mitochondrial metabolism (ATP5B), oxidative stress (GPX4), apoptosis (DAD1, DAP, PRDX2), heat shock (HSPA5), pregnancy (IFNT2, PAG2) and cell differentiation (KRT18) varied between experimental groups.

scholarly journals Agastache rugosa alleviates the multi-hit effect on hepatic lipid metabolism, inflammation and oxidative stress during nonalcoholic fatty liver disease

2020 ◽  
Author(s):  
Yizhe Cui ◽  
Renxu Chang ◽  
Qiuju Wang ◽  
Yusheng Liang ◽  
Juan J Loor ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Lipid Metabolism ◽  
Liver Disease ◽  
Fatty Liver ◽  
Lipid Accumulation ◽  
Liver Tissue ◽  
Fatty Liver Disease ◽  
Agastache Rugosa

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease, and has high rates of morbidity and mortality worldwide. Agastache rugosa (AR) possesses unique anti-oxidant, anti‑inflammatory and anti-atherosclerosis characteristics. Methods To investigate the effects and the underlying mechanism of AR on NAFLD, we fed mice a high-fat diet (HFD) to establish NAFLD model of mice in vivo experiment and induced lipidosis in AML12 hepatocytes through a challenge with free fatty acids (FFA) in vitro. The contents of total cholesterol (TC), triglyceride (TG), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in liver homogenates were measured. Pathological changes in liver tissue were evaluated by HE staining. Oil red O staining was used to determine degree of lipid accumulation in liver tissue, and Western blot was used to detect abundance of inflammation-, lipid metabolism- and endoplasmic reticulum stress-related proteins. Results Supply of AR alleviated accumulation of lipid in hepatocytes induced by HFD in vivo and challenged with free fatty acids (FFA) in vitro. Compared with the HFD group, supplementing AR decreased p-NF-κB/NF-κB and p-IκB/IκB protein and inhibited abundance of PERK, IRE1 and ATF6 (P < 0.05). Furthermore, AR reduced lipid accumulation within hepatocytes by downregulating abundance of SREBP, ACC1 and FAS (P < 0.05). Supply of AR significantly attenuated ROS accumulation and MDA production by improving antioxidant enzymatic activity including SOD and GSH (P < 0.01). Conclusion Supply of AR attenuates disordered lipid metabolism and enhances the antioxidative defense associated with NAFLD induced by HFD in mice. Results underscore the potential of plants used in traditional Chinese medicine to achieve pharmacological benefits through a multi-tier cellular response.

scholarly journals Akt1 and Akt2 Isoforms Play Distinct Roles in Regulating the Development of Inflammation and Fibrosis Associated with Alcoholic Liver Disease

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1337 ◽  
Author(s):  
Karina Reyes-Gordillo ◽  
Ruchi Shah ◽  
Jaime Arellanes-Robledo ◽  
Ying Cheng ◽  
Joseph Ibrahim ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Liver Disease ◽  
Alcoholic Liver Disease ◽  
Kupffer Cells ◽  
Mammalian Target Of Rapamycin ◽  
Akt Isoforms ◽  
And Migration ◽  
Phosphoinositide 3 Kinase

Akt kinase isoforms (Akt1, Akt2, and Akt3) have generally been thought to play overlapping roles in phosphoinositide 3-kinase (PI3K)-mediated-signaling. However, recent studies have suggested that they display isoform-specific roles in muscle and fat. To determine whether such isoform-specificity is observed with respect to alcoholic liver disease (ALD) progression, we examined the role of Akt1, Akt2, and Akt3 in hepatic inflammation, and pro-fibrogenic proliferation and migration using Kupffer cells, hepatic stellate cells (HSC), and hepatocytes in an ethanol and lipopolysaccharide (LPS)-induced two-hit model in vitro and in vivo. We determined that siRNA-directed silencing of Akt2, but not Akt1, significantly suppressed cell inflammatory markers in HSC and Kupffer cells. Although both Akt1 and Akt2 inhibited cell proliferation in HSC, only Akt2 inhibited cell migration. Both Akt1 and Akt2, but not Akt3, inhibited fibrogenesis in hepatocytes and HSC. In addition, our in vivo results show that administration of chronic ethanol, binge ethanol and LPS (EBL) in wild-type C57BL/6 mice activated all three Akt isoforms with concomitant increases in activated forms of phosphoinositide dependent kinase-1 (PDK1), mammalian target-of-rapamycin complex 2 (mTORC2), and PI3K, resulting in upregulation in expression of inflammatory, proliferative, and fibrogenic genes. Moreover, pharmacological blocking of Akt2, but not Akt1, inhibited EBL-induced inflammation while blocking of both Akt1 and Akt2 inhibited pro-fibrogenic marker expression and progression of fibrosis. Our findings indicate that Akt isoforms play unique roles in inflammation, cell proliferation, migration, and fibrogenesis during EBL-induced liver injury. Thus, close attention must be paid when targeting all Akt isoforms as a therapeutic intervention.

Sign in / Sign up

Export Citation Format

Share Document