Development of an in vitro model to study hepatitis C virus effects on hepatocellular lipotoxicity and lipid metabolism

2018 ◽  
Vol 214 (10) ◽  
pp. 1700-1706 ◽  
Author(s):  
Leandra Koletzko ◽  
Abdo Mahli ◽  
Claus Hellerbrand
Keyword(s):  
Hepatitis C Virus ◽  
Lipid Metabolism ◽  
Hepatitis C ◽  
In Vitro Model ◽  
Vitro Model

scholarly journals Future Directions in the Treatment of Patients with Chronic Hepatitis C Virus Infection

1999 ◽  
Vol 13 (1) ◽  
pp. 57-62 ◽  
Author(s):  
Robert G Gish
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
High Throughput Screening ◽  
In Vitro Model ◽  
Single Agent ◽  
Protein Translation ◽  
In Vitro Translation ◽  
Biotechnology Companies ◽  
Vitro Model

Hepatitis C virus (HCV) infects over 170 million people worldwide. While interferon is currently the most used single agent therapy, this drug may result in a sustained loss of virus from the blood in only up to 15% of patients; new options for treatment are needed. With the release of ribavirin in North America and Europe, a viral clearance rate or ‘cure’ may be attained in up to 40% of patients. Developing successful antiviral therapy that prevents or delays the development of cirrhosis, liver failure and liver cancer as well as decreasing the demand for liver transplantation are clearly identified goals. Unfortunately, there is no complete in vitro model of HCV replication or translation. Due to the lack of an animal or cell culture model of HCV infection, in vitro translation screening systems to identify inhibitors of HCV protein translation are being evaluated by a large number of biotechnology companies. With advancing computer technology, high throughput screening processes are now possible and can be joined to specific in vitro model testing systems. Along with examining some of the information known about HCV therapy and the HCV genome, the present review discusses potential targets for new therapies and identifies therapeutic agents that are nearing clinical application

scholarly journals An in vitro model of hepatitis C virus genotype 3a-associated triglycerides accumulation

2005 ◽  
Vol 42 (5) ◽  
pp. 744-751 ◽  
Author(s):  
Karim Abid ◽  
Valerio Pazienza ◽  
Andrea de Gottardi ◽  
Laura Rubbia-Brandt ◽  
Beatrice Conne ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
In Vitro Model ◽  
Virus Genotype ◽  
Vitro Model ◽  
Genotype 3A

868 LIVER X RECEPTOR a-MEDIATED LIPOGENESIS INDUCED BY HEPATITIS C VIRUS NS5A AND CORE PROTEINS REGULATES VIRAL REPLICATION IN AN IN VITRO MODEL

2012 ◽  
Vol 56 ◽  
pp. S338
Author(s):  
S. Pisonero-Vaquero ◽  
M.V. García-Mediavilla ◽  
F. Jorquera ◽  
P.L. Majano ◽  
J. Gonzalez-Gallego ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Viral Replication ◽  
In Vitro Model ◽  
Liver X Receptor ◽  
Core Proteins ◽  
Vitro Model

scholarly journals In-vitro model systems to study Hepatitis C Virus

2011 ◽  
Vol 9 (1) ◽  
Author(s):  
Usman Ali Ashfaq ◽  
Shaheen N Khan ◽  
Zafar Nawaz ◽  
Sheikh Riazuddin
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
In Vitro Model ◽  
Model Systems ◽  
Vitro Model

An in vitro model of glucose and lipid metabolism in a multicompartmental bioreactor

2011 ◽  
Vol 7 (1) ◽  
pp. 117-126 ◽  
Author(s):  
Bruna Vinci ◽  
Ellen Murphy ◽  
Elisabetta Iori ◽  
Francesco Meduri ◽  
Silvia Fattori ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
In Vitro Model ◽  
Glucose And Lipid Metabolism ◽  
Vitro Model

scholarly journals Rituximab Treatment in Hepatitis C Infection: An In Vitro Model to Study the Impact of B Cell Depletion on Virus Infectivity

PLoS ONE ◽  
2011 ◽  
Vol 6 (9) ◽  
pp. e25789 ◽  
Author(s):  
Zania Stamataki ◽  
Samantha Tilakaratne ◽  
David H. Adams ◽  
Jane A. McKeating
Keyword(s):  
Hepatitis C ◽  
B Cell ◽  
In Vitro Model ◽  
Cell Depletion ◽  
Virus Infectivity ◽  
B Cell Depletion ◽  
Hepatitis C Infection ◽  
Vitro Model ◽  
The Impact

scholarly journals SUN-550 CARF Through Its Lipid Lowering Effect May Play a Pivotal Role in the Development of Non-Alcoholic Fatty Liver Diseases

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Kamrul M Hasan ◽  
Meher Parveen ◽  
Alondra Pena ◽  
Amiya P Sinha-Hikim ◽  
Theodore C Friedman
Keyword(s):  
Lipid Metabolism ◽  
Fatty Liver ◽  
Hepg2 Cells ◽  
In Vitro Model ◽  
Lipid Lowering ◽  
Alcoholic Fatty Liver ◽  
Lowering Effect ◽  
Vitro Model ◽  
Lipid Lowering Effect

Abstract CARF (Collaborator of ARF), a member of ARF-MDM2-p53 pathway and an emerging multifunctional protein, regulates cellular fate in response to various stresses including oxidative DNA damage and replicative stresses. However, its role in metabolic syndrome (MS) and associated diseases has not been studied. This study, using our well established in vivo and in vitro model systems, examines the role of CARF in the development of non-alcoholic fatty liver disease (NAFLD). Indeed, we have found that, compared to control, CARF expression along with Sirt1, pAMPK and pACC (common biological markers of NAFLD) was significantly decreased in the nicotine and high-fat-diet (HFD) in combination or HFD alone induced fatty livers. Additionally, CARF expression was down regulated in palmitate (PA)-treated HepG2 cells, an in vitro model of steatosis, suggesting that CARF expression is negatively regulated in MS, such as NAFLD. Our study further revealed that shRNA mediated knockdown or lentiviral mediated over expression of CARF induced or reduced endogenous fat accumulation, respectively, in HepG2 cells. We also found that overexpression of CARF lowered the exogenous fat accumulation in PA treated HepG2 cells. RNA seq analysis after CARF knockdown in HEK-293T cells further revealed that genes associated with lipid metabolism and triglyceride (TG) synthesis such as diacylglycerol O-acyltransferase2 (DGAT2), acyl-CoA synthetase long-chain family member 4 and 6 (ACSL4, ACSL6) were upregulated in CARF-depleted cells. Likewise, we also found increased expression of DGAT2 in CARF-depleted HepG2 cells, which enhanced TG synthesis. Intriguingly, consistent with the lipid lowering effects of metformin, an antidiabetic drug, we further found that CARF expression along with pAMPK and Sirt1 were significantly increased in metformin-treated HepG2 cells. However, we also found increased pACC levels in CARF over-expressing cells which was further enhanced in metformin-treated cells, suggesting, for the first time, that CARF may contribute to lipid lowering effect of metformin by inhibiting lipogenesis. We conclude that CARF has a lipid lowering effect in hepatocytes and its down regulation in response to MS perturbs lipid metabolism that may lead to the development of NAFLD.

Sign in / Sign up

Export Citation Format

Share Document