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

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

来源：International Journal of Molecular Medicine, 2011, 27(5): 619-624.

DOI：10.3892/ijmm.2011.622

• cannabinoid
• cannabinoid receptor 1
• hepatitis C virus
• triglyceride
• Huh7
• replicon

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 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 endocannabinoid/cannabinoid receptor signaling pathway. In this study, we examined the expression of a cannabinoid receptor (CBI.) and the lipid accumulation in the hepatic Huh7 cell line, expressing HCV genes. We utilized Huh7/Rep-Feo-lb 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-lb cells compared to Huh7 cells. Also, triglyceride accumulation and CBI receptor expression were down-regulated in Huh7/Rep-Teo-lb cells after HCV reduction by IFN alpha. Moreover, lipid accumulation appeared to increase after CBI agonist treatment, while it decreased after CBI 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.

• 出版日期2011-5