title: Association between lipid accumulation and the cannabinoid system in Huh7 cells expressing HCV genes.
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 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 (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.
authors.affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan.
authors.forename: Mako
authors.initials: M
authors.lastname: Toyoda
authors.forename: Akira
authors.initials: A
authors.lastname: Kitaoka
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Machida
authors.forename: Takuya
authors.initials: T
authors.lastname: Nishinakagawa
authors.forename: Ryoko
authors.initials: R
authors.lastname: Yada
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Kohjima
authors.forename: Masaki
authors.initials: M
authors.lastname: Kato
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kotoh
authors.forename: Naoya
authors.initials: N
authors.lastname: Sakamoto
authors.forename: Goshi
authors.initials: G
authors.lastname: Shiota
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakamuta
authors.forename: Manabu
authors.initials: M
authors.lastname: Nakashima
authors.forename: Munechika
authors.initials: M
authors.lastname: Enjoji
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology; D001095:Arachidonic Acids / Q000494:pharmacology; D045744:Cell Line, Tumor; D004318:Doxycycline / Q000494:pharmacology; D020869:Gene Expression Profiling; D015967:Gene Expression Regulation, Viral; D016174:Hepacivirus / Q000235:genetics*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D050356:Lipid Metabolism; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism; D014758:Viral Core Proteins / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000378:metabolism; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D001095:Arachidonic Acids; D004318:Doxycycline; D016898:Interferon-alpha; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D014280:Triglycerides; D014758:Viral Core Proteins; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C093542:NS4 protein, hepatitis C virus; C119325:arachidonyl-2-chloroethylamide; C069130:nucleocapsid protein, Hepatitis C virus; C103505:AM 251; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase