Background and aims: Obesity-related hepatic steatosis is commonly associated with central fat accumulation and alteration of adipocytokine secretion; however, the connection between non-obese hepatic steatosis and adipocytokine remains unclear. We aim to investigate this connection using an animal model of conditional HCV core transgenic mice.
Methods: Double transgenic mice (DTM), in which hepatic over-expression of the hepatitis C virus (HCV) core protein is regulated by doxycycline, were given normal chow diet following 1 month of a doxycycline-rich diet. The mice exhibited non-obese hepatic steatosis at 2 months of age. The levels of leptin and adiponectin were assessed in 2-month-old DTM (i.e., HCV core-tetracycline transactivator [tTA]) and single transgenic mice (STM; i.e., tTA). The total fat mass and the body fat distribution of the mice were evaluated using dual-energy X-ray absorptiometry and magnetic resonance imaging. Microarray analyses and quantitative real-time polymerase chain reaction were conducted using RNA obtained from the visceral fat of paired DTM and STM. Adiponectin was administered intraperitoneally to the 2-month-old DTM.
Results: No significant differences of the various fat components were noted between the DTM and STM. The DTM exhibited down-regulated leptin mRNA of the visceral fat and reduced adiponectin serum protein levels compared with the STM. Adiponectin treatment also significantly ameliorated hepatic steatosis in the DTM compared to the controls.
Conclusions: HCV core-induced non-obese hepatic steatosis is associated with down-regulation of the leptin gene in visceral fat and concurrent hypoadiponectinemia; however, these effects may be ameliorated by adiponectin treatment.