Increased Phosphoenolpyruvate Carboxykinase Gene Expression and Steatosis during Hepatitis C Virus Subgenome Replication

Qadri, Ishtiaq; Choudhury, Mahua; Rahman, Shaikh Mizanoor; Janssen, Rachel C.; Schaack, Jerome; Iwahashi, Mieko; Puljak, Livia; Simon, Francis R.; Kilic, Gordan; Fitz, John; Friedman, Jacob E.

doi:10.1074/jbc.m112.384743

Cited by 20 publications

(12 citation statements)

References 60 publications

(64 reference statements)

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“…It predisposes the infected to both type 1 diabetes mellitus (T1DM) and T2DM (Antonelli et al 2014). PGC-1α expression is dramatically elevated in HCV-infected cells, accompanied by an upregulated expression of PEPCK and G6Pase (Qadri et al 2012, Shlomai et al 2012. In addition, the HCV nonstructural protein 5A induces metabolic dysregulation and IR in human hepatoma cells, in which PGC-1α could be involved (Parvaiz et al 2014).…”

Section: Hepatitis C Virusmentioning

confidence: 97%

PGC-1α, glucose metabolism and type 2 diabetes mellitus

Deng

Shi

et al. 2016

Journal of Endocrinology

135

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Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by glucose metabolic disturbance. A number of transcription factors and coactivators are involved in this process. Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) is an important transcription coactivator regulating cellular energy metabolism. Accumulating evidence has indicated that PGC-1α is involved in the regulation of T2DM. Therefore, a better understanding of the roles of PGC-1α may shed light on more efficient therapeutic strategies. Here, we review the most recent progress on PGC-1α and discuss its regulatory network in major glucose metabolic tissues such as the liver, skeletal muscle, pancreas and kidney. The significant associations between PGC-1α polymorphisms and T2DM are also discussed in this review.

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Section: Hepatitis C Virusmentioning

confidence: 97%

PGC-1α, glucose metabolism and type 2 diabetes mellitus

Deng

Shi

et al. 2016

Journal of Endocrinology

135

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“…Interestingly, these small molecules were unexpected pCREB could promote HCV-induced gluconeogenic gene expression [49].…”

Section: T1:12mentioning

confidence: 99%

Molecular mechanisms of hepatic apoptosis regulated by nuclear factors

Wang

2015

Cellular Signalling

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“…Its presence is a key prognostic indicator associated with the progression to hepatic fibrosis and hepatocellular carcinoma (44). Several mechanisms have been proposed to account for the development of steatosis and fatty liver observed during HCV infection (45,46). HCV infection enhances lipogenesis, reduces secretion of very-low-density lipoprotein, attenuates ␤-oxidation of lipid, and increases virus growth and replication through complex pathways that intersect via modulating host cell lipid metabolism (47,48).…”

Section: Discussionmentioning

confidence: 99%

Forkhead Box Transcription Factor Regulation and Lipid Accumulation by Hepatitis C Virus

Bose

Kim

Meyer

et al. 2014

J Virol

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We have previously shown that hepatitis C virus (HCV) infection modulates the expression of forkhead box transcription factors, including FoxO1 and FoxA2, which play key roles in gluconeogenesis and ␤-oxidation of fatty acid, respectively. The aim of the present study was to determine the role of forkhead box transcription factors in modulating lipid metabolism. HCV infection or core protein expression alone in transfected Huh7. H epatitis C virus (HCV)is an important cause of morbidity and mortality worldwide, causing a spectrum of disease ranging from an asymptomatic carrier state to end-stage liver disease (1-4). The most important feature of HCV infection is the development of chronic hepatitis in a significant number of infected individuals and the potential for disease progression to metabolic disorders, fibrosis/cirrhosis, and hepatocellular carcinoma (1-3, 5). We have previously shown that HCV modulates signaling pathways in inducing insulin resistance (6, 7).Insulin regulates the expression of key enzymes involved in glucose and lipid metabolism by modulating the activity of specific forkhead box transcription factors (FoxO1 and FoxA2) in the liver. FoxO1 mediates the expression of genes involved in both glucose and lipid metabolism in the liver (8, 9). Insulin suppresses the expression of key gluconeogenic enzymes, including glucose 6-phosphatase (G6P) and phosphoenolpyruvate carboxykinase (PCK2), by stimulating the translocation of FoxO1 outside the nucleus (10). Increased glucose production can activate genes involved in lipid metabolism, including sterol regulatory element binding protein 1c (SREBP-1c) and fatty acid synthase (FASN).On the other hand, FoxA2 controls hepatic lipid metabolism in type 2 diabetes, improving insulin resistance (11,12). Thus, an interruption in insulin signaling may affect metabolic regulation. During chronic HCV infection, insulin resistance may elicit a vicious cycle for manipulating the functions of FoxA2, preventing optimal stimulation of normal metabolic functions of the liver. Lipid homeostasis requires balancing metabolic vectors, including lipogenesis, export, and degradation (␤-oxidation), a significant component of which is orchestrated by a family of membrane-bound master regulator transcription factors designated sterol regulatory element binding proteins (SREBPs) that regulate the expression of more than 30 genes involved in the synthesis and uptake of cholesterol, fatty acids, triglycerides, and phospholipids

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Increased Phosphoenolpyruvate Carboxykinase Gene Expression and Steatosis during Hepatitis C Virus Subgenome Replication

Cited by 20 publications

References 60 publications

PGC-1α, glucose metabolism and type 2 diabetes mellitus

PGC-1α, glucose metabolism and type 2 diabetes mellitus

Molecular mechanisms of hepatic apoptosis regulated by nuclear factors

Forkhead Box Transcription Factor Regulation and Lipid Accumulation by Hepatitis C Virus

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