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Hepatitis C virus proteins induce lipogenesis and defective triglyceride secretion in transgenic mice
- Source :
- Journal of Biological Chemistry, Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2009, 284 (48), pp.33466-74. ⟨10.1074/jbc.M109.019810⟩, Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2009, 284 (48), pp.33466-74. 〈10.1074/jbc.M109.019810〉, Journal of Biological Chemistry, 2009, 284 (48), pp.33466-74. ⟨10.1074/jbc.M109.019810⟩
- Publication Year :
- 2009
- Publisher :
- HAL CCSD, 2009.
-
Abstract
- This research was originally published in The Journal of Biological Chemistry. © the American Society for Biochemistry and Molecular Biology; International audience; Chronic hepatitis C virus (HCV) infection is associated with altered lipid metabolism and hepatocellular steatosis. Virus-induced steatosis is a cytopathic effect of HCV replication. The goal of this study was to examine the mechanisms underlying HCV-induced lipid metabolic defects in a transgenic mouse model expressing the full HCV protein repertoire at levels corresponding to natural human infection. In this model, expression of the HCV full-length open reading frame was associated with hepatocellular steatosis and reduced plasma triglyceride levels. Triglyceride secretion was impaired, whereas lipogenesis was activated. Increased lipogenic enzyme transcription was observed, resulting from maturational activation and nuclear translocation of sterol regulatory element-binding protein 1c (SREBP1c). However, endoplasmic reticulum (ER) stress markers were expressed at similar levels in both HCV transgenic mice and their wild type counterparts, suggesting that SREBP1c proteolytic cleavage in the presence of HCV proteins was independent of ER stress. In conclusion, transgenic mice expressing the HCV full-length polyprotein at low levels have decreased plasma triglyceride levels and develop hepatocellular steatosis in the same way as HCV-infected patients. In these mice, SREBP1c activation by one or several HCV proteins induces de novo triglyceride synthesis via the lipogenic pathway, in a manner independent of ER stress, whereas triglyceride secretion is simultaneously reduced.
- Subjects :
- Male
medicine.medical_specialty
Transgene
Blotting, Western
Mice, Transgenic
Lipids and Lipoproteins: Metabolism, Regulation, and Signaling
Hepacivirus
Biology
Endoplasmic Reticulum
Biochemistry
Mice
Viral Proteins
03 medical and health sciences
0302 clinical medicine
Internal medicine
[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology
medicine
Animals
Humans
Secretion
[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
[ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology
Molecular Biology
Triglycerides
030304 developmental biology
Cytopathic effect
0303 health sciences
Reverse Transcriptase Polymerase Chain Reaction
Lipogenesis
Fatty liver
virus diseases
Lipid metabolism
Cell Biology
medicine.disease
Hepatitis C
Virology
digestive system diseases
3. Good health
Fatty Liver
Mice, Inbred C57BL
Disease Models, Animal
Endocrinology
Liver
Unfolded protein response
030211 gastroenterology & hepatology
Steatosis
Sterol Regulatory Element Binding Protein 1
Subjects
Details
- Language :
- English
- ISSN :
- 00219258 and 1083351X
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry, Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2009, 284 (48), pp.33466-74. ⟨10.1074/jbc.M109.019810⟩, Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2009, 284 (48), pp.33466-74. 〈10.1074/jbc.M109.019810〉, Journal of Biological Chemistry, 2009, 284 (48), pp.33466-74. ⟨10.1074/jbc.M109.019810⟩
- Accession number :
- edsair.doi.dedup.....c526df4a2c168878bfbf2cc1b469d6d2
- Full Text :
- https://doi.org/10.1074/jbc.M109.019810⟩