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 ◽  
...  
2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Renin Chang ◽  
Mei-Chia Chou ◽  
Li-Ying Hung ◽  
Mu-En Wang ◽  
Meng-Chieh Hsu ◽  
...  

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.


ChemInform ◽  
2010 ◽  
Vol 30 (27) ◽  
pp. no-no
Author(s):  
Ichiji Namatame ◽  
Hiroshi Tomoda ◽  
Shuyi Si ◽  
Yuichi Yamaguchi ◽  
Rokuro Masuma ◽  
...  

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

2017 ◽  
Vol 44 (4) ◽  
pp. 1651-1664 ◽  
Author(s):  
Guo-yi Wu ◽  
Chen Rui ◽  
Ji-qiao Chen ◽  
Eiketsu Sho ◽  
Shan-shan Zhan ◽  
...  

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.


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

2017 ◽  
Vol 84 (3) ◽  
pp. 283-288 ◽  
Author(s):  
Jung Nam Lee ◽  
Yong Wang ◽  
Ya Ou Xu ◽  
Yu Can Li ◽  
Fang Tian ◽  
...  

This research communication describes the profile of gene expression related to the synthesis of yak milk as determined via quantitative reverse transcription polymerase chain reaction (RT-qPCR). Significant up-regulation during lactation were observed in genes related to fatty acid (FA) uptake from blood (LPL, CD36), intracellular FA transport (FABP3), intracellular FA activation of long- and short-chain FAs (ACSS1, ACSS2, ACSL1), de novo synthesis (ACACA), desaturation (SCD), triacyglycerol (TAG) synthesis (AGPAT6, GPAM, LPIN1), lipid droplet formation (PLIN2, BTN1A1, XDH), ketone body utilisation (BDH1, OXCT1), and transcription regulation (THRSP, PPARGC1A). In particular, intracellular de novo FA synthesis (ACSS2, ACACA, and FABP3) and TAG synthesis (GPAM, AGPAT6, and LPIN1), whose regulation might be orchestrated as part of the gene network under the control of SERBF1 in the milk fat synthesis process, were more activated compared to levels in dairy cows. However, the genes involved in lipid droplet formation (PLIN2, XDH, and BTN1A1) were expressed at lower levels compared to those in dairy cows, where these genes are mainly controlled by the PPARG regulator.


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