Association between lipid accumulation and the cannabinoid system in Huh7 cells expressing HCV genes

Mako Toyoda, Akira Kitaoka, Kazuyuki Machida, Takuya Nishinakagawa, Ryoko Yada, Motoyuki Kohjima, Masaki Kato, Kazuhiro Kotoh, Naoya Sakamoto, Goshi Shiota, Makoto Nakamuta, Manabu Nakashima, Munechika Enjoji

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11 Citations (Scopus)

Abstract

Evidence from clinical and laboratory studies has accumulated indicating that the activation of the cannabinoid system is crucial for steatosis, especially in non-alcoholic fatty liver disease. However, the association between hepatitis C C virus (HCV) infection and the cannabinoid system has not been well investigated and it is unclear whether steatosis in chronic hepatitis C develops via activation of the endo-cannabinoid/cannabinoid receptor signaling pathway. In this study, we examined the expression of a cannabinoid receptor (CB1) and the lipid accumulation in the hepatic Huh7 cell line, expressing HCV genes. We utilized Huh7/Rep-Feo-1b cells stably expressing HCV non-structural proteins (NS) 3, NS4, NS5A, and NS5B, as well as Tet-On Core-2 cells, in which the HCV core protein expression is inducible. Significantly higher levels of stored triglycerides were found in Huh7/Rep-Feo-1b cells compared to Huh7 cells. Also, triglyceride accumulation and CB1 receptor expression were down-regulated in Huh7/Rep-Feo-1b cells after HCV reduction by IFNα. Moreover, lipid accumulation appeared to increase after CB1 agonist treatment, while it decreased after CB1 antagonist treatment, although significant differences were not found compared to untreated cells. In Tet-On Core-2 cells, induction of HCV core protein expression did not affect CB1 expression or triglyceride accumulation. The results of this study in cultured cells suggest that HCV infection may activate the cannabinoid system and precede steatosis, but the core protein by itself may not have any effect on the cannabinoid system.

Original languageEnglish
Pages (from-to)619-624
Number of pages6
JournalInternational journal of molecular medicine
Volume27
Issue number5
DOIs
Publication statusPublished - May 2011

All Science Journal Classification (ASJC) codes

  • Genetics

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    Toyoda, M., Kitaoka, A., Machida, K., Nishinakagawa, T., Yada, R., Kohjima, M., Kato, M., Kotoh, K., Sakamoto, N., Shiota, G., Nakamuta, M., Nakashima, M., & Enjoji, M. (2011). Association between lipid accumulation and the cannabinoid system in Huh7 cells expressing HCV genes. International journal of molecular medicine, 27(5), 619-624. https://doi.org/10.3892/ijmm.2011.622