Infection with HIV and HCV enhances the release of fatty acid synthase into circulation: evidence for a novel indicator of viral infection

Abstract

BackgroundFatty acid synthase (FASN) is an enzyme synthesized by the liver and plays an important role in lipogenesis. The present study aimed to investigate whether serum FASN concentration may provide a direct link between HIV and/or HCV viral infections and lipid metabolic disorders commonly observed in HIV/HCV-infected patients.MethodsWe evaluated serum FASN concentration in 191 consecutive HIV-infected patients in the absence or presence of HCV co-infection. For comparison, 102 uninfected controls were included. Metabolic and inflammatory phenotype was also compared with respect to the presence of HCV co-infection.ResultsSerum FASN concentration was significantly higher in HIV-infected patients than in healthy participants and HCV co-infected patients showed higher levels than those without co-infection. Levels were also affected by treatment regimen, but marginally influenced by virological variables. Insulin concentration was the sole variable among metabolic parameters that demonstrated a significant correlation with serum FASN concentrations. Serum alanine aminotransferase (ALT) values correlated significantly with serum FASN concentration and provided the best discrimination with respect to the presence or absence of HCV co-infection. In multivariate analysis, only ALT, monocyte chemoattractant protein-1 (MCP-1) and the presence of antiretroviral treatment regimen significantly contributed to explain serum FASN concentration in HIV/HCV co-infected patients.ConclusionSerum FASN concentration is significantly increased in HIV-infected individuals. The release of FASN into the circulation is further enhanced in patients who are co-infected with HCV. Subsequent studies should explore the usefulness of this indicator to monitor the effect of viral infections on disease progression and survival.

Hepatitis C Virus Replication Is Modulated by the Interaction of Nonstructural Protein NS5B and Fatty Acid Synthase

“…FASN expression is significantly increased in HCV-infected livers (37), and serum FASN concentrations are significantly increased in patients with chronic HCV infection (38,39). FASN is also upregulated in HCV-infected Huh7 cells (18).…”

Serum fatty acid synthase concentration is increased in patients with hepatitis viral infection and may assist in the prediction of liver steatosis

“…11,12 It has been previously demonstrated in vitro that FASN is upregulated in cells infected with HIV, HCV and HBV, 5,6,13 and we have recently proposed that the release of FASN into circulation is a novel indicator of viral infection in humans. 4 We have found in this study that serum FASN shows a significant predictive value for liver steatosis, and may segregate patients with different degree of steatosis. Such effects are not independent of increased serum ALT.…”

“…3 More recently, we have found that serum FASN concentration is significantly increased in HIV-infected individuals, and that the release of FASN into the circulation is further enhanced in patients who are co-infected with HCV. 4 However, we did not find any association with metabolic stress. Furthermore, it has been demonstrated in vitro that FASN is up-regulated during hepatitis C virus (HCV) infection and regulates HCV entry and production.…”

“…10 Serum FASN concentration and alanine aminotransferase (ALT) were measured as previously described. 4 Although samples have been stored from 1.2 to 4.8 years, an influence of storage is unlikely as the decrease in values (n = 15) measured after 2 years of storage was not significant [at 7.9%: in ng/mL, 21.3 (7.6) in baseline, and 19.6 (8.1) after two years of storage]. Results are expressed as mean (SD) unless otherwise indicated.…”

Lipids and RNA virus replication

“…Fatty acid synthase (FASN) is a key lipogenic enzyme involved in fatty acids synthesis (Table 1; Figure 1A). Indeed, FASN protein levels are increased in HCV-infected patients [20,21] or HCV-infected cells [22,23]. Notably, Nasheri et al found that HCV NS4B was involved in FASN induction and concomitant increase in fatty acids production [23].…”