scholarly journals Study of Valproic Acid-Enhanced Hepatocyte Steatosis

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Renin Chang ◽  
Mei-Chia Chou ◽  
Li-Ying Hung ◽  
Mu-En Wang ◽  
Meng-Chieh Hsu ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Lipid Droplet ◽  
Fatty Acid Synthase ◽  
Molecular Mechanisms ◽  
Nuclear Translocation ◽  
Droplet Formation ◽  
Dependent Manner ◽  
Lipid Uptake ◽  
Lipid Droplet Formation ◽  
Hepatocyte Steatosis

Valproic acid (VPA) is one of the most widely used antiepilepsy drugs. However, several side effects, including weight gain and fatty liver, have been reported in patients following VPA treatment. In this study, we explored the molecular mechanisms of VPA-induced hepatic steatosis using FL83B cell line-basedin vitromodel. Using fluorescent lipid staining technique, we found that VPA enhanced oleic acid- (OLA-) induced lipid accumulation in a dose-dependent manner in hepatocytes; this may be due to upregulated lipid uptake, triacylglycerol (TAG) synthesis, and lipid droplet formation. Real-time PCR results showed that, following VPA treatment, the expression levels of genes encoding cluster of differentiation 36 (Cd36), low-density lipoprotein receptor-related protein 1 (Lrp1), diacylglycerol acyltransferase 2 (Dgat2), and perilipin 2 (Plin2) were increased, that of carnitine palmitoyltransferase Ia(Cpt1a) was not affected, and those of acetyl-Co A carboxylaseα(Acca) and fatty acid synthase (Fasn) were decreased. Furthermore, using immunofluorescence staining and flow cytometry analyses, we found that VPA also induced peroxisome proliferator-activated receptorγ(PPARγ) nuclear translocation and increased levels of cell-surface CD36. Based on these results, we propose that VPA may enhance OLA-induced hepatocyte steatosis through the upregulation of PPARγ- and CD36-dependent lipid uptake, TAG synthesis, and lipid droplet formation.

scholarly journals Conserved valproic-acid-induced lipid droplet formation in Dictyostelium and human hepatocytes identifies structurally active compounds

2011 ◽  
Vol 5 (2) ◽  
pp. 231-240 ◽  
Author(s):  
L. M. Elphick ◽  
N. Pawolleck ◽  
I. A. Guschina ◽  
L. Chaieb ◽  
D. Eikel ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Lipid Droplet ◽  
Droplet Formation ◽  
Human Hepatocytes ◽  
Active Compounds ◽  
Lipid Droplet Formation

ChemInform Abstract: Beauveriolides, Specific Inhibitors of Lipid Droplet Formation in Mouse Macrophages, Produced by Beauveria sp. FO-6979.

ChemInform ◽  
2010 ◽  
Vol 30 (27) ◽  
pp. no-no
Author(s):  
Ichiji Namatame ◽  
Hiroshi Tomoda ◽  
Shuyi Si ◽  
Yuichi Yamaguchi ◽  
Rokuro Masuma ◽  
...  
Keyword(s):  
Lipid Droplet ◽  
Droplet Formation ◽  
Lipid Droplet Formation ◽  
Mouse Macrophages ◽  
Specific Inhibitors

Norepinephrine induces calcium spikes and proinflammatory actions in human hepatic stellate cells

2006 ◽  
Vol 291 (5) ◽  
pp. G877-G884 ◽  
Author(s):  
Pau Sancho-Bru ◽  
Ramón Bataller ◽  
Jordi Colmenero ◽  
Xavier Gasull ◽  
Montserrat Moreno ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Portal Hypertension ◽  
Liver Fibrosis ◽  
Hepatic Stellate Cells ◽  
Molecular Mechanisms ◽  
Nuclear Translocation ◽  
Stellate Cells ◽  
Luciferase Reporter ◽  
Dependent Manner ◽  
Cell Contraction

Catecholamines participate in the pathogenesis of portal hypertension and liver fibrosis through α1-adrenoceptors. However, the underlying cellular and molecular mechanisms are largely unknown. Here, we investigated the effects of norepinephrine (NE) on human hepatic stellate cells (HSC), which exert vasoactive, inflammatory, and fibrogenic actions in the injured liver. Adrenoceptor expression was assessed in human HSC by RT-PCR and immunocytochemistry. Intracellular Ca2+ concentration ([Ca2+]i) was studied in fura-2-loaded cells. Cell contraction was studied by assessing wrinkle formation and myosin light chain II (MLC II) phosphorylation. Cell proliferation and collagen-α1(I) expression were assessed by [3H]thymidine incorporation and quantitative PCR, respectively. NF-κB activation was assessed by luciferase reporter gene and p65 nuclear translocation. Chemokine secretion was assessed by ELISA. Normal human livers expressed α1A-adrenoceptors, which were markedly upregulated in livers with advanced fibrosis. Activated human HSC expressed α1A-adrenoceptors. NE induced multiple rapid [Ca2+]i oscillations (Ca2+ spikes). Prazosin (α1-blocker) completely prevented NE-induced Ca2+ spikes, whereas propranolol (nonspecific β-blocker) partially attenuated this effect. NE caused phosphorylation of MLC II and cell contraction. In contrast, NE did not affect cell proliferation or collagen-α1(I) expression. Importantly, NE stimulated the secretion of inflammatory chemokines (RANTES and interleukin-8) in a dose-dependent manner. Prazosin blocked NE-induced chemokine secretion. NE stimulated NF-κB activation. BAY 11-7082, a specific NF-κB inhibitor, blocked NE-induced chemokine secretion. We conclude that NE stimulates NF-κB and induces cell contraction and proinflammatory effects in human HSC. Catecholamines may participate in the pathogenesis of portal hypertension and liver fibrosis by targeting HSC.

P0952 : Transient hepatic overexpression of the insuline-like growth factor 2 (IGF2) induces lipid droplet formation

2015 ◽  
Vol 62 ◽  
pp. S702-S703 ◽  
Author(s):  
S.M. Kessler ◽  
S. Laggai ◽  
E. Van Wonterghem ◽  
R.E. Vandenbroucke ◽  
M. Ogris ◽  
...  
Keyword(s):  
Growth Factor ◽  
Lipid Droplet ◽  
Droplet Formation ◽  
Lipid Droplet Formation

scholarly journals MicroRNA-122 Inhibits Lipid Droplet Formation and Hepatic Triglyceride Accumulation via Yin Yang 1

2017 ◽  
Vol 44 (4) ◽  
pp. 1651-1664 ◽  
Author(s):  
Guo-yi Wu ◽  
Chen Rui ◽  
Ji-qiao Chen ◽  
Eiketsu Sho ◽  
Shan-shan Zhan ◽  
...  
Keyword(s):  
Quantitative Pcr ◽  
Lipid Droplet ◽  
Droplet Formation ◽  
Luciferase Assay ◽  
Luciferase Reporter ◽  
Hepatic Triglyceride ◽  
Yin Yang 1 ◽  
Lipid Droplet Formation ◽  
Huh7 Cells ◽  
Yin Yang

Background/Aims: An increase in intracellular lipid droplet formation and hepatic triglyceride (TG) content usually results in nonalcoholic fatty liver disease. However, the mechanisms underlying the regulation of hepatic TG homeostasis remain unclear. Methods: Oil red O staining and TG measurement were performed to determine the lipid content. miRNA expression was evaluated by quantitative PCR. A luciferase assay was performed to validate the regulation of Yin Yang 1 (YY1) by microRNA (miR)-122. The effects of miR-122 expression on YY1 and its mechanisms involving the farnesoid X receptor and small heterodimer partner (FXR-SHP) pathway were evaluated by quantitative PCR and Western blot analyses. Results: miR-122 was downregulated in free fatty acid (FFA)-induced steatotic hepatocytes, and streptozotocin and high-fat diet (STZ-HFD) induced nonalcoholic steatohepatitis (NASH) in mice. Transfection of hepatocytes with miR-122 mimics before FFA induction inhibited lipid droplet formation and TG accumulation in vitro. These results were verified by overexpressing miR-122 in the livers of STZ-HFD-induced NASH mice. The 3’-untranslated region (3’UTR) of YY1 mRNA is predicted to contain an evolutionarily conserved miR-122 binding site. In silico searches, a luciferase reporter assay and quantitative PCR analysis confirmed that miR-122 directly bound to the YY1 3’UTR to negatively regulate YY1 mRNA in HepG2 and Huh7 cells. The (FXR-SHP) signaling axis, which is downstream of YY1, may play a key role in the mechanism of miR-122-regulated lipid homeostasis. YY1-FXR-SHP signaling, which is negatively regulated by FFA, was enhanced by miR-122 overexpression. This finding was also confirmed by overexpression of miR-122 in the livers of NASH mice. Conclusions: The present results indicate that miR-122 plays an important role in lipid (particularly TG) accumulation in the liver by reducing YY1 mRNA stability to upregulate FXR-SHP signaling.

scholarly journals Perilipin1 promotes unilocular lipid droplet formation through the activation of Fsp27 in adipocytes

2013 ◽  
Vol 4 (1) ◽  
Author(s):  
Zhiqi Sun ◽  
Jingyi Gong ◽  
Han Wu ◽  
Wenyi Xu ◽  
Lizhen Wu ◽  
...  
Keyword(s):  
Lipid Droplet ◽  
Droplet Formation ◽  
Lipid Droplet Formation
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