Hepatitis B virus inhibits the in vivo and in vitro synthesis and secretion of apolipoprotein C3

Abstract

BackgroundHepatitis B virus (HBV) infection in the body can damage liver cells and cause disorders in blood lipid metabolism. Apolipoprotein C3 (ApoC3) plays an important role in the regulation of lipid metabolism, but no study on the HBV regulation of ApoC3 has been reported. This purpose of this study was to investigate the effect of HBV on ApoC3 expression and its regulatory mechanism.MethodsThe expression levels of ApoC3 mRNA and protein in the human hepatoma cell lines HepG2 and HepG2.2.15 were determined using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot. The HepG2 cells were co-transfected with the ApoC3 gene promoter and either HBV-infected clone pHBV1.3 or its individual genes. The changes in luciferase activity were assayed. The expression levels of ApoC3 mRNA and protein were determined using RT-qPCR and Western blot. The content of ApoC3 in the supernatant of the cultured cells was determined using an enzyme-linked immunosorbent assay (ELISA). The sera were collected from 149 patients with HBV infection and 102 healthy subjects at physical examination as the normal controls. The serological levels of ApoC3 in the HBV group and the normal control group were determined using ELISA. The contents of serum triglyceride (TG) and very-low-density lipoprotein (VLDL) in the HBV patients and the normal control were determined using an automatic biochemical analyser.ResultsThe expression levels of ApoC3 mRNA and protein were lower in the HepG2.2.15 cells than in the HepG2 cells. pHBV1.3 and its X gene could inhibit the activity of the ApoC3 promoter and its mRNA and protein expression. The serum levels of ApoC3, VLDL and TG were 65.39 ± 7.48 μg/ml, 1.24 ± 0.49 mmol/L, and 0.46 ± 0.10 mmol/L in the HBV patients and 41.02 ± 6.88 μg/ml, 0.76 ± 0.21 mmol/L, 0.29 ± 0.05 mmol/L in the normal controls, respectively, statistical analysis revealed significantly lower serum levels of ApoC3, VLDL and TG in HBV patients than in the normal controls (P < 0.05).ConclusionHBV can inhibit the in vivo and in vitro synthesis and secretion of ApoC3.

Serum apolipoprotein C3 levels are negatively associated with hepatitis B virus DNA in HBeAg-negative chronic hepatitis B patients

“…Previous study has clearly shown that a decrease in ApoC3 is associated with a significant decrease in TG levels [25]. It is indicated that HBV down-regulated the synthesis and secretion of ApoC3 via its X gene and lower serum levels of ApoC3 and TG were observed in CHB patients [15]. In our study, we found that serum ApoC3 and TG levels in CHB patients were decreased, which is in accordance with the above results.…”

“…ApoC3 and ApoA5 are associated with multiple lipid metabolism-related diseases, such as type 1 diabetes and coronary artery disease [11–13]. Although previous study showed that HBV inhibits ApoA5 and ApoC3 promoter activity and mRNA and protein expression through its core gene [14] or X gene [15], respectively, little was revealed about the association between ApoC3 or ApoA5 and HBV replication rate in CHB patients.…”

Multifaceted Interaction Between Hepatitis B Virus Infection and Lipid Metabolism in Hepatocytes: A Potential Target of Antiviral Therapy for Chronic Hepatitis B

“…Hepatocytes are the major sites of apolipoprotein synthesis and lipoprotein assembly, secretion, uptake, and catabolism. Some clinical studies in HBV-infected population have found significantly decreased levels of plasma ApoA1 (Jiang et al, 2014;Wang Y. et al, 2016;Cui et al, 2019), ApoA5 (Zhu et al, 2016;Cui et al, 2019), ApoB (Wang et al, 2011;Cui et al, 2019), and ApoC3 (Zhu et al, 2017;Cui et al, 2019), whereas dramatically increased level of serum ApoM or ApoE (Gu et al, 2011;Shen et al, 2016). These results from clinical studies were consistent with observations from several experimental studies.…”

“…ApoC3 acted as an inhibitor of lipoprotein lipase (LPL), which was a crucial enzyme in TG lipoprotein catabolism ( Larsson et al, 2017 ). A study ( Zhu et al, 2017 ) showed that HBV inhibited the synthesis and secretion of ApoC3. Therefore, during chronic HBV infection, a decrease in ApoC3 expression would increase LPL activity, decrease VLDL synthesis and secretion, and increase TG decomposition.…”

Insulin resistance exhibits varied metabolic abnormalities in nonalcoholic fatty liver disease, chronic hepatitis B and the combination of the two: a cross-sectional study

“…Our findings reinforce those of previous studies demonstrating that HBV infection is negatively associated with hypertriglyceridemia [26] and provide evidence that HBV infection negates the promoting effect of IR on TG levels. One possible mechanism explaining this phenomenon is that HBV products, including HBV protein X, interrupt de-novo lipid synthesis and secretion under insulin-resistant conditions, which are characterized by inhibition of Apo-C3 expression [27] and Apo-B secretion [28]. As the major protein component of triglyceride (TG)-rich lipoproteins, decreased Apo-B and Apo-C3 concentrations therefore lower serum very-low-density lipoprotein (VLDL) and TG levels.…”