Hepatitis C virus core protein genotype 3a increases SOCS-7 expression through PPAR-  in Huh-7 cells

Pazienza, Valerio; Vinciguerra, Manlio; Andriulli, Angelo; Mangia, Alessandra

doi:10.1099/vir.0.020644-0

Cited by 62 publications

(41 citation statements)

References 34 publications

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“…A HCV genotype specific mechanism of impairment of insulin signaling was observed, since expression of the HCV genotype 3 core protein led to downregulation of PPARγ and upregulation of SOCS-7, while the core protein of genotype 1 activated mTOR and induced phosphorylation of IRS-1 at inhibitory serine residues [42]. Subsequent work suggested that PPARγ may directly control the SOCS-7 level in cells expressing the HCV genotype 3 core [46]. It was later shown that the activation of SOCS family members may be a mechanism common to all major HCV genotypes [47], including genotype 1, since the variant originally associated with mTOR activation was shown to be infrequent among known isolates.…”

Section: Molecular Mechanisms Of Hcv-induced Insulin Resistancementioning

confidence: 99%

Review article Insulin resistance and its consequences in chronic hepatitis C

Kukla¹,

Piotrowski²,

Waluga³

et al. 2015

ceh

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Chronic hepatitis C (CHC) is generally a slowly progressive disease, but some factors associated with rapid progression have been identified. Hepatitis C virus (HCV) may contribute to a broad spectrum of metabolic disturbances – namely, steatosis, insulin resistance (IR), increased prevalence of impaired glucose tolerance, type 2 diabetes mellitus (T2DM), lipid metabolism abnormalities and atherosclerosis.HCV can directly or indirectly cause both IR and steatosis, but it is still not resolved whether this viral impact bears the same prognostic value as the metabolic counterparts. As the population exposed to HCV ages, the morbidity due to this disease is increasing. The rising epidemic of obesity contributes to higher prevalence of IR and T2DM. Our understanding of the mutual association between both disease states continues to grow, but is still far from complete. This review briefly discusses the most probable mechanisms involved in IR development in the course of CHC. Molecular mechanisms for the direct and indirect influence of HCV on intracellular insulin signaling are described. Subsequently, the consequences of IR/T2DM for disease progression and management are summarized.

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Section: Molecular Mechanisms Of Hcv-induced Insulin Resistancementioning

confidence: 99%

Review article Insulin resistance and its consequences in chronic hepatitis C

Kukla¹,

Piotrowski²,

Waluga³

et al. 2015

ceh

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“…HCV genotype 3 promotes down-regulation of IRS1 by up-regulating SOCS7 but not SOCS3 (Figure 1) [52] . SOCS-7 mRNA expression is independent of signal transducer and activator of transcription 3 and is modulated by peroxisome proliferator-activated receptor gamma activity (Figure 1) [52,55] . HCV genotype 4 is the most common variant in the Middle East and Africa and is increasing in prevalence in Western countries [56] .…”

Section: Pathogenesis Of Insulin Resistance In Patients With Chronic mentioning

confidence: 99%

Insulin resistance and chronic liver disease

Kawaguchi

Taniguchi²,

Itou³

et al. 2011

WJH

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Increased insulin resistance is frequently associated with chronic liver disease and is a pathophysiological feature of hepatogenous diabetes. Distinctive factors including hepatic parenchymal cell damage, portalsystemic shunting and hepatitis C virus are responsible for the development of hepatogenous insulin resistance/ diabetes. Although it remains unclear whether insulin secretion from pancreatic beta cells is impaired as it is in type 2 diabetes, retinopathic and cardiovascular risk is low and major causes of death in cirrhotic patients with diabetes are liver failure, hepatocellular carcinoma and gastrointestinal hemorrhage. Hemoglobin A1c is an inaccurate marker for the assessment and management of hepatogenous diabetes. Moreover, exogenous insulin or sulfonylureas may be harmful because these agents may promote hepatocarcinogenesis. Thus, pathogenesis, cause of death, assessment and therapeutic strategy for hepatogenous insulin resistance/diabetes differ from those for lifestyle-related type 2 diabetes. In this article, we review features of insulin resistance in relationship to chronic liver disease. We also discuss the impact of anti-diabetic agents on interferon treatment and hepatocarcinogenesis.

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“…(2) Increased PPARc mRNA expression in liver tissues of CHC patients is associated with HCV-induced steatosis by way of PPARc-up-regulated lipogenic genes that are effectors of lipid accumulation (Lima-Cabello et al, 2011). However, HCV core protein down-regulates PPARc in Huh7 cells, leading to induction of suppressor of cytokine signaling 7, which is repressed by PPARc (Pazienza et al, 2010). PPARb agonist attenuates palmitic acid-induced fatty accumulation in HepG2 cells by anti-inflammatory mechanism (Lee et al, 2012).…”

Section: Discussionmentioning

confidence: 98%