Impaired expression of the peroxisome proliferator–activated receptor alpha during hepatitis C virus infection

Dharancy, Sébastien; Malapel, Mathilde; Perlemuter, Gabriel; Roskams, Tania; Cheng, Yang; Dubuquoy, Laurent; Podevin, Philippe; Conti, Filoména; Canva, V.; Philippe, David; Gambiez, L; Mathurin, Philippe; Paris, J; Schoonjans, Kristina; Calmus, Yvon; Pol, Stanislas; Auwerx, Johan; Desreumaux, Pierre

doi:10.1053/j.gastro.2004.11.016

Cited by 195 publications

(164 citation statements)

References 62 publications

Supporting

Mentioning

150

Contrasting

Unclassified

Order By: Relevance

“…Hepatic concentrations of PPARα and its downstream target-gene CPT1A expressed by hepatocytes were impaired profoundly in the livers of untreated patients with HCV infection compared with controls [122]. In mice, liver-specific transgenic expression of the HCV core protein induced hepatic steatosis in all animals and HCC development in 35% of them [123].…”

Section: Peroxisome-proliferator-activated Receptors (Ppars)mentioning

confidence: 99%

From the metabolic syndrome to NAFLD or vice versa?

Vanni

Bugianesi

Kotronen

et al. 2010

Digestive and Liver Disease

433

351

View full text Add to dashboard Cite

The metabolic syndrome encompasses metabolic and cardiovascular risk factors which predict diabetes and cardiovascular disease (CVD) better than any of its individual components. Nonalcoholic fatty liver disease (NAFLD) comprises a disease spectrum which includes variable degrees of simple steatosis (nonalcoholic fatty liver, NAFL), nonalcoholic steatohepatitis (NASH) and cirrhosis. NAFLD is the hepatic manifestation of the metabolic syndrome, with insulin resistance as the main pathogenetic mechanism. Recent data indicate that hyperinsulinemia is probably the consequence rather than cause of NAFLD and NAFLD can be considered an independent predictor of cardiovascular disease. Serum free fatty acids derived from lipolysis of visceral adipose tissue are the main source of hepatic triglycerides in NAFLD, although hepatic de novo lipogenesis and dietary fat supply contribute to the pathogenesis of NAFLD. Approximately 10-25% NAFLD patients develop NASH, the evolutive form of hepatic steatosis. Presumably in a genetically predisposed environment, this increased lipid overload overwhelms the oxidative capacity and reactive oxygen species are generated, leading to lipid peroxidation, cytokine induction, chemoattraction of inflammatory cells, hepatic stellate cell activation and finally fibrogenesis with extracellular matrix deposition. No currently available therapies for NAFLD and NASH exist. Recently nuclear receptors have emerged as key regulators of lipid and carbohydrate metabolism for which specific pharmacological ligands are available, making them attractive therapeutic targets for NAFLD and NASH.Abbreviations ALT, alanine aminotransferase; BMI, body mass index; CVD, cardiovascular disease; FFA, free fatty acids; HDL, high density lipoprotein; 1H-MRS, proton magnetic resonance spectroscopy; IDF, International Diabetes Federation; LDL, low density lipoprotein; NAFLD, nonalcoholic fatty liver disease; SNP, single nucleotide polymorphism; VLDL, very low density lipoprotein IntroductionThe metabolic syndrome is a cluster of metabolic and cardiovascular risk factors which predicts diabetes and cardiovascular disease (CVD) better than any of its individual components [1]. The latest definition of the metabolic syndrome by International Diabetes Federation (IDF) includes abdominal obesity defined by increased waist circumference (≥94 cm in men and ≥80 cm in women) and two or more of the following features: elevated blood pressure, fasting glucose or triglyceride concentrations, or low HDL cholesterol [1]. The term nonalcoholic fatty liver disease (NAFLD) comprises a disease spectrum which includes variable degrees of simple steatosis (nonalcoholic fatty liver, NAFL), nonalcoholic steatohepatitis (NASH) and cirrhosis [2] and [3]. NAFLD can be considered the hepatic manifestation of the metabolic syndrome. Simple steatosis is benign, whereas NASH is defined by the presence of hepatocyte injury, inflammation and/or fibrosis which can lead to cirrhosis, liver failure and hepatocellular carcinoma. In contrast to t...

show abstract

Section: Peroxisome-proliferator-activated Receptors (Ppars)mentioning

confidence: 99%

From the metabolic syndrome to NAFLD or vice versa?

Vanni

Bugianesi

Kotronen

et al. 2010

Digestive and Liver Disease

433

351

View full text Add to dashboard Cite

show abstract

“…Several groups have shown that HCV infection leads to the reduction of β-oxidation by downregulating the expression of the transcription factor PPARα (peroxisome-proliferator-activated receptor α). 87,97,98 Moreover, the AMP-activated protein kinase (AMPK), a key regulator of lipid metabolism which augments fatty acid oxidation, appears to be inactive (dephosphorylated) in HCV-infected cells. Thus, inhibition of AMPK by HCV would favor a reduction in fatty acid oxidation and thus an increase in hepatic lipid accumulation.…”

Section: Role Of Lipid Metabolism In Hcv Rna Replicationmentioning

confidence: 99%

Hepatitis c virus and host cell lipids: An intimate connection

Alvisi¹,

Madan²,

2011

View full text Add to dashboard Cite

“…97 In fact, both the peroxisome proliferatoractivated receptor-alpha (PPARa) and sterol regulatory element binding protein (SREBP) pathways (Fig. 2) have been shown to be modulated during HCV replication and infection.…”

Section: Genomic Approachesmentioning

confidence: 99%

Host–virus interactions during hepatitis C virus infection: a complex and dynamic molecular biosystem

2010

View full text Add to dashboard Cite

The hepatitis C virus (HCV) is a global health issue with no vaccine available and limited clinical treatment options. Like other obligate parasites, HCV requires host cellular components of an infected individual to propagate. These host-virus interactions during HCV infection are complex and dynamic and involve the hijacking of host cell environments, enzymes and pathways. Understanding this unique molecular biosystem has the potential to yield new and exciting strategies for therapeutic intervention. Advances in genomics and proteomics have opened up new possibilities for the rapid measurement of global changes at the transcriptional and translational levels during infection. However, these techniques only yield snapshots of host-virus interactions during HCV infection. Other new methods that involve the imaging of biomolecular interactions during HCV infection are required to identify key interactions that may be transient and dynamic. Herein we highlight systems biology based strategies that have helped to identify key host-virus interactions during HCV replication and infection. Novel biophysical tools are also highlighted for identification and visualization of activities and interactions between HCV and its host hepatocyte. As some of these methods mature, we expect them to pave the way forward for further exploration of this complex biosystem and elucidation of mechanisms for HCV pathogenesis and carcinogenesis.

show abstract

Impaired expression of the peroxisome proliferator–activated receptor alpha during hepatitis C virus infection

Cited by 195 publications

References 62 publications

From the metabolic syndrome to NAFLD or vice versa?

From the metabolic syndrome to NAFLD or vice versa?

Hepatitis c virus and host cell lipids: An intimate connection

Host–virus interactions during hepatitis C virus infection: a complex and dynamic molecular biosystem

Contact Info

Product

Resources

About