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Condition: Fatty Liver Disease (FLD)

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Total 185 results found since Jan 2013.

Hepatocyte-protective effect of nectandrin B, a nutmeg lignan, against oxidative stress: Role of Nrf2 activation through ERK phosphorylation and AMPK-dependent inhibition of GSK-3 β.
This study investigated the hepatocyte-protective effect of nectandrin B against tert-butylhydroperoxide-induced oxidative injury and the underlying molecular mechanism. The cell viability assay revealed that nectandrin B prevents apoptosis stimulated by tert-butylhydroperoxide in both HepG2 cells and primary mouse hepatocytes. Nectandrin B also attenuated ROS production and restored the depleted glutathione level. Real-time PCR and immunoblot analyses showed that the expression of glutamate-cysteine ligase, an enzyme responsible for the glutathione biosynthesis, was induced by nectandrin B, indicating its indirect antioxi...
Source: Toxicology and Applied Pharmacology - August 6, 2016 Category: Toxicology Authors: Song JS, Kim EK, Choi YW, Oh WK, Kim YM Tags: Toxicol Appl Pharmacol Source Type: research

Receptor interacting protein 3 protects mice from high fat diet‐induced liver injury
Conclusion: Absence of RIP3, a key mediator of necroptosis, exacerbated HFD‐induced liver injury, associated with increased inflammation and hepatocyte apoptosis, as well as early fibrotic responses. These findings indicate that shifts in the mode of hepatocellular death can influence disease progression and have therapeutic implications because manipulation of hepatocyte cell death pathways is being considered as a target for treatment of NAFLD. This article is protected by copyright. All rights reserved.
Source: Hepatology - June 14, 2016 Category: Internal Medicine Authors: Sanjoy Roychowdhury, Rebecca L. McCullough, Carlos Sanz‐Garcia, Paramananda Saikia, Naim Alkhouri, Ammar Matloob, Katherine Pollard, Megan R. McMullen, Colleen M. Croniger, Laura E. Nagy Tags: Steatohepatitis and Metabolic Liver Disease Source Type: research

Hedgehog signaling is a potent regulator of liver lipid metabolism and reveals a GLI-code associated with steatosis
This study assessed the unexpected role of the Hedgehog pathway in adult liver lipid metabolism. Using transgenic mice with conditional hepatocyte-specific deletion of Smoothened in adult mice, we showed that hepatocellular inhibition of Hedgehog signaling leads to steatosis by altering the abundance of the transcription factors GLI1 and GLI3. This steatotic 'Gli-code' caused the modulation of a complex network of lipogenic transcription factors and enzymes, including SREBP1 and PNPLA3, as demonstrated by microarray analysis and siRNA experiments and could be confirmed in other steatotic mouse models as well as in steatoti...
Source: eLife - May 17, 2016 Category: Biomedical Science Tags: Biochemistry Cell Biology Hedgehog signalling hepatocytes Human liver Mouse NAFLD smoothened steatotic Gli-code Source Type: research

SIRT3 Regulates Hepatic Stellate Cell Activation Metabolism
In this study, we aimed to establish whether SIRT3 regulated the SDH activity, succinate, and GPR91 expression in HSCs and an animal model of NAFLD. Our goal was also to determine whether succinate released from hepatocytes regulated HSC activation. Inhibiting SIRT3 using SIRT3 siRNA exacerbated HSC activation via the SDH-succinate-GPR91 pathway, and SIRT3 overexpression or honokiol treatment attenuated HSC activation in vitro. In isolated liver and HSCs from methionine- and choline-deficient (MCD) diet-induced NAFLD, the expression of SIRT3 and SDH activity was decreased, and the succinate concentrations and GPR91 express...
Source: Journal of Biological Chemistry - May 5, 2016 Category: Chemistry Authors: Li, Y. H., Choi, D. H., Lee, E. H., Seo, S. R., Lee, S., Cho, E.-H. Tags: Cell Biology Source Type: research

Hyperhomocysteinemia activates the aryl hydrocarbon receptor/CD36 pathway to promote hepatic steatosis in mice
Conclusion: In conclusion, our results strongly suggest that HHcy activated the AHR‐CD36 pathway by increasing hepatic LXA4 content, which resulted in HS. (Hepatology 2016; 00:000–000)
Source: Hepatology - April 4, 2016 Category: Internal Medicine Authors: Liu Yao, Chunjiong Wang, Xu Zhang, Liyuan Peng, Wenli Liu, Xuejiao Zhang, Yajin Liu, Jinlong He, Changtao Jiang, Ding Ai, Yi Zhu Tags: Steatohepatitis and Metabolic Liver Disease Source Type: research

Punicalagin attenuates palmitate‐induced lipotoxicity in HepG2 cells by activating the Keap1‐Nrf2 antioxidant defense system
Conclusions: These findings suggest that punicalagin could effectively attenuate FFA‐induced lipotoxicity by activating Keap1‐Nrf2 cytoprotective signaling pathway.This article is protected by copyright. All rights reserved
Source: Nahrung / Food - March 15, 2016 Category: Nutrition Authors: Chunhong Yan, Wenyan Sun, Xun Wang, Jiangang Long, Xuebo Liu, Zhihui Feng, Jiankang Liu Tags: Research Article Source Type: research

Palmitate-induced Regulation of PPARγ via PGC1α: a Mechanism for Lipid Accumulation in the Liver in Nonalcoholic Fatty Liver Disease.
In conclusion, palmitate appear to up-regulate PPARγ via PGC1α in Huh7 cells, and both PGC1α and PPARγ are up-regulated in the NAFLD mice liver, suggesting an effect on lipid metabolism leading to intrahepatic triglyceride accumulation. PMID: 26941577 [PubMed - in process]
Source: International Journal of Medical Sciences - March 6, 2016 Category: Biomedical Science Tags: Int J Med Sci Source Type: research

Hyperhomocysteinemia Activates the Aryl Hydrocarbon Receptor‐CD36 Pathway to Promote Hepatic Steatosis in Mice
In conclusion, our results strongly suggest that HHcy activated the AHR‐CD36 pathway by increasing hepatic LXA4 content, which resulted in hepatic steatosis. This article is protected by copyright. All rights reserved.
Source: Hepatology - February 29, 2016 Category: Internal Medicine Authors: Liu Yao, Chunjiong Wang, Xu Zhang, Liyuan Peng, Wenli Liu, Xuejiao Zhang, Yajin Liu, Jinlong He, Changtao Jiang, Ding Ai, Yi Zhu Tags: Steatohepatitis and Metabolic Liver Disease Source Type: research

miR-212 downregulation contributes to the protective effect of exercise against non-alcoholic fatty liver via targeting FGF-21.
In this study, normal or high-fat diet (HF) mice were either subjected to a 16-week running program or kept sedentary. Exercise attenuated liver steatosis in HF mice. MicroRNA array and qRT-PCR demonstrated that miR-212 was overexpressed in HF liver, while reduced by exercise. Next, we investigated the role of miR-212 in lipogenesis using HepG2 cells with/without long-chain fatty acid treatment (±FFA). FFA increased miR-212 in HepG2 cells. Moreover, miR-212 promoted lipogenesis in HepG2 cells (±FFA). Fibroblast growth factor (FGF)-21, a key regulator for lipid metabolism, was negatively regulated by miR-212 at protein le...
Source: J Cell Mol Med - December 9, 2015 Category: Molecular Biology Authors: Xiao J, Bei Y, Liu J, Dimitrova-Shumkovska J, Kuang D, Zhou Q, Li J, Yang Y, Xiang Y, Wang F, Yang C, Yang W Tags: J Cell Mol Med Source Type: research

Hydrogen sulfide reduces serum triglyceride by activating liver autophagy via the AMPK-mTOR pathway
Autophagy plays an important role in liver triglyceride (TG) metabolism. Inhibition of autophagy could reduce the clearance of TG in the liver. Hydrogen sulfide (H2S) is a potent stimulator of autophagic flux. Recent studies showed H2S is protective against hypertriglyceridemia (HTG) and noalcoholic fatty liver disease (NAFLD), while the mechanism remains to be explored. Here, we tested the hypothesis that H2S reduces serum TG level and ameliorates NAFLD by stimulating liver autophagic flux by the AMPK-mTOR pathway. The level of serum H2S in patients with HTG was lower than that of control subjects. Sodium hydrosulfide (Na...
Source: AJP: Endocrinology and Metabolism - December 1, 2015 Category: Endocrinology Authors: Sun, L., Zhang, S., Yu, C., Pan, Z., Liu, Y., Zhao, J., Wang, X., Yun, F., Zhao, H., Yan, S., Yuan, Y., Wang, D., Ding, X., Liu, G., Li, W., Zhao, X., Liu, Z., Li, Y. Tags: Articles Source Type: research

Deletion of sphingosine kinase 1 ameliorates hepatic steatosis in diet-induced obese mice: Role of PPARγ
Publication date: Available online 23 November 2015 Source:Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids Author(s): Jinbiao Chen, Wei Wang, Yanfei Qi, Dominik Kaczorowski, Geoffrey W. McCaughan, Jennifer R. Gamble, Anthony S. Don, Xin Gao, Mathew A. Vadas, Pu Xia Sphingolipid metabolites have emerged playing important roles in the pathogenesis of nonalcoholic fatty liver disease, whereas the underlying mechanism remains largely unknown. In the present study, we provide both in vitro and in vivo evidence showing a pathogenic role of sphingosine kinase 1 (SphK1) in hepatocellular stea...
Source: Biochimica et Biophysica Acta (BBA) Molecular and Cell Biology of Lipids - November 25, 2015 Category: Lipidology Source Type: research

Deletion of sphingosine kinase 1 ameliorates hepatic steatosis in diet-induced obese mice: Role of PPARγ.
Abstract Sphingolipid metabolites have emerged playing important roles in the pathogenesis of nonalcoholic fatty liver disease, whereas the underlying mechanism remains largely unknown. In the present study, we provide both in vitro and in vivo evidence showing a pathogenic role of sphingosine kinase 1 (SphK1) in hepatocellular steatosis. We found that levels of SphK1 expression were significantly increased in steatotic hepatocytes. Enforced overexpression of SphK1 or treatment with sphingosine 1-phosphate (S1P) markedly enhanced hepatic lipid accumulation. In contrast, the siRNA-mediated knockdown of SphK1 or S1P...
Source: Biochimica et Biophysica Acta - November 23, 2015 Category: Biochemistry Authors: Chen J, Wang W, Qi Y, Kaczorowski D, McCaughan GW, Gamble JR, Don AS, Gao X, Vadas MA, Xia P Tags: Biochim Biophys Acta Source Type: research

RNA Interference as a Therapeutic Strategy for the Treatment of Liver Diseases.
Abstract RNA interference has emerged as an innovative technology for gene silencing that degrades mRNAs complementary to the antisense strands of double-stranded, short interfering RNAs (siRNAs). Its therapeutic application has important advantages over small-molecule drugs since offers the possibility of targeting virtually all genes and allows selective silencing of one or several genes. So far, a relative small proportion of cellular proteins can bind and respond to chemical drugs. Based on that, RNA interference-mediated gene silencing is widely considered as a crucial breakthrough in molecular biology with a...
Source: Current Pharmaceutical Design - October 23, 2015 Category: Drugs & Pharmacology Authors: Gonzalez-Rodriguez A, Valverde AM Tags: Curr Pharm Des Source Type: research

Post-transcriptional HAMP Regulation by PA Is Mediated via HuR Gene Regulation
In conclusion, lipids mediate post-transcriptional regulation of HAMP throughPKC- and HuR-dependent mechanisms.
Source: Journal of Biological Chemistry - October 2, 2015 Category: Chemistry Authors: Lu, S., Mott, J. L., Harrison-Findik, D. D. Tags: Metabolism Source Type: research

Glucagon‐like peptide‐1 preserves non‐alcoholic fatty liver disease through inhibition of the endoplasmic reticulum stress‐associated pathway
ConclusionGLP‐1 protected against NAFLD by inactivating the ER stress‐associated apoptosis pathway. In addition, the effect was possibly related to the signaling pathway of ERp46.
Source: Hepatology Research - August 18, 2015 Category: Internal Medicine Authors: Na Ao, Jing Yang, Xiaochen Wang, Jian Du Tags: Original Article Source Type: research