Metabolic Disorders and Steatosis in Patients with Chronic Hepatitis C: Metabolic Strategies for Antiviral Treatments

Enjoji, Munechika; Kohjima, Motoyuki; Kotoh, Kazuhiro; Nakamuta, Makoto

doi:10.1155/2012/264017

Cited by 13 publications

(7 citation statements)

References 84 publications

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“…This in turn deregulates fatty acid synthesis and leads to hepatic steatosis. In parallel, the HCV core protein increases the activity of peroxisome proliferator-activating receptor (PPAR)–alpha and gamma in hepatocytes contributing to deregulation of fatty acid beta-oxydation and insulin sensitivity (for a review see [46]). Finally, Fujino et al demonstrated that lipid metabolism genes like the SREBP family genes expression are modified through this mechanism [26].…”

Section: Lipids Apolipoproteins and Hcv Pathogenesismentioning

confidence: 99%

Hepatitis C Virus, Cholesterol and Lipoproteins — Impact for the Viral Life Cycle and Pathogenesis of Liver Disease

Felmlee

Hafirassou

Lefèvre

et al. 2013

Viruses

132

119

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Hepatitis C virus (HCV) is a leading cause of chronic liver disease, including chronic hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Hepatitis C infection associates with lipid and lipoprotein metabolism disorders such as hepatic steatosis, hypobetalipoproteinemia, and hypocholesterolemia. Furthermore, virus production is dependent on hepatic very-low-density lipoprotein (VLDL) assembly, and circulating virions are physically associated with lipoproteins in complexes termed lipoviral particles. Evidence has indicated several functional roles for the formation of these complexes, including co-opting of lipoprotein receptors for attachment and entry, concealing epitopes to facilitate immune escape, and hijacking host factors for HCV maturation and secretion. Here, we review the evidence surrounding pathogenesis of the hepatitis C infection regarding lipoprotein engagement, cholesterol and triglyceride regulation, and the molecular mechanisms underlying these effects.

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Section: Lipids Apolipoproteins and Hcv Pathogenesismentioning

confidence: 99%

Hepatitis C Virus, Cholesterol and Lipoproteins — Impact for the Viral Life Cycle and Pathogenesis of Liver Disease

Felmlee

Hafirassou

Lefèvre

et al. 2013

Viruses

132

119

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“…The best characterized of these receptors are the cannabinoid 1 receptor and the cannabinoid 2 receptor . Although traditionally associated with the central nervous system (CNS), cannabinoid receptors in hepatocytes are increasingly being recognized as key mediators of fatty liver and associated insulin resistance caused by high‐fat diet , viral hepatitis and ethanol intake . Additionally, cannabis smoking has been shown to be a risk factor for hepatic steatosis and, in a separate study, patients with non‐alcoholic fatty liver disease were found to have a 34.2 ± 9.7‐fold increase in the amount of hepatic CB 1 R mRNA compared with patients without liver pathology .…”

Section: The Role Of Cannabinoid Receptors In Fatty Livermentioning

confidence: 99%

The hepatic cannabinoid 1 receptor as a modulator of hepatic energy state and food intake

Cooper

Regnell

2013

Brit J Clinical Pharma

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The cannabinoid 1 receptor (CB1R) has a well-established role in appetite regulation. Central CB1R antagonists, notably rimonabant, induced weight loss and improved the metabolic profile in obese individuals, but were discontinued due to psychiatric side-effects. The CB1R is also expressed peripherally, where its effects include promotion of liver fat accumulation, which consumes ATP. Type 2 diabetes in obese subjects is linked to excess liver fat, whilst there is a negative correlation between hepatic ATP content and insulin resistance. A decreased hepatic ATP/AMP ratio increases food intake by signals via the vagus nerve to the brain. The hepatic cannabinoid system is highly upregulated in obesity, and the effects of hepatic CB1R activation include increased activity of lipogenic and gluconeogenic transcription factors. Thus, blockade of hepatic CB1Rs could contribute significantly to the weight-reducing and insulin-sensitizing effects of CB1R antagonists. Additionally, upregulation of the hepatic CB1R may contribute to chronic liver inflammation, fibrosis and cirrhosis from causes including obesity, alcoholism and viral hepatitis. Peripheral CB1R antagonists induce weight loss and metabolic improvements in obese rodents; however, as there is evidence that hepatic CB1Rs are predominately intracellular, due to high intrinsic clearance, many drugs may not effectively block these receptors and therefore have limited efficacy. Hepatoselective CB1R antagonists may be effective at reducing hepatic steatosis, insulin resistance and bodyweight in obese, diabetic patients, with far fewer side-effects than first-generation CB1R antagonists. Additionally, such compounds may be effective in treating inflammatory liver disease, such as non-alcoholic steatohepatitis, reducing the likelihood of disease progression to cirrhosis or cancer. Hepatic energy state and its effects on food intakeThe cellular energy state is defined by adenine nucleotide levels. Healthy cells maintain a ratio of ATP to ADP of the order of 10:1. Cellular concentrations of ADP typically remain constant, while ATP and AMP levels deviate in reciprocal directions [1].Hepatic energy state influences food intake [2, 3]. For instance, infusion of various lipids and carbohydrates into the hepatic portal vein of rodents was found to suppress food intake more effectively than administration of the same nutrients into the jugular vein [2]. Supporting results were found when injecting the fructose analogue 2,5-anhydro-D-mannitol (2,5-AM) into the portal vein. In the liver, 2,5-AM is phosphorylated at the 1 and 6 positions, but not metabolized further, thus lowering the levels of free intracellular phosphates, which reduces the generation of ATP, whilst increasing its degradation by disinhibiting adenosine deaminase. The net result is a lower hepatocellular ATP concentration, which increases feeding [4]. Pretreatment with sodium phosphate prevents the decrease in liver ATP levels and the increase in feeding [5]. Administration of the amino-acid analogue L-ethionin...

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“…Additionally, HCV infection induces activation of sterol regulatory element binding protein (SREBP), the transcription factor responsible for lipogenesis [ 20 , 21 , 22 ]. Downregulation of carnitine palmitoyltransferase expression may additionally increase steatosis by inhibition of beta-oxidation [ 23 ]. Overproduction of lipid droplets has also been observed in HCV-transfected cells.…”

Section: Lipid Phenotype Of Chronic Hcv Patientsmentioning

confidence: 99%

Hepatitis C Virus Uses Host Lipids to Its Own Advantage

Sidorkiewicz

2021

Metabolites

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Lipids and lipoproteins constitute indispensable components for living not only for humans. In the case of hepatitis C virus (HCV), the option of using the products of our lipid metabolism is “to be, or not to be”. On the other hand, HCV infection, which is the main cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma, exerts a profound influence on lipid and lipoprotein metabolism of the host. The consequences of this alternation are frequently observed as hypolipidemia and hepatic steatosis in chronic hepatitis C (CHC) patients. The clinical relevance of these changes reflects the fact that lipids and lipoprotein play a crucial role in all steps of the life cycle of HCV. The virus circulates in the bloodstream as a highly lipidated lipo-viral particle (LVP) that defines HCV hepatotropism. Thus, strict relationships between lipids/lipoproteins and HCV are indispensable for the mechanism of viral entry into hepatocytes, viral replication, viral particles assembly and secretion. The purpose of this review is to summarize the tricks thanks to which HCV utilizes host lipid metabolism to its own advantage.

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Metabolic Disorders and Steatosis in Patients with Chronic Hepatitis C: Metabolic Strategies for Antiviral Treatments

Cited by 13 publications

References 84 publications

Hepatitis C Virus, Cholesterol and Lipoproteins — Impact for the Viral Life Cycle and Pathogenesis of Liver Disease

Hepatitis C Virus, Cholesterol and Lipoproteins — Impact for the Viral Life Cycle and Pathogenesis of Liver Disease

The hepatic cannabinoid 1 receptor as a modulator of hepatic energy state and food intake

Hepatitis C Virus Uses Host Lipids to Its Own Advantage

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