Abstract:

[Objective] Ultraviolet resistance-associated gene (UVRAG) is an autophagy-related protein with multiple functions. Previously that autophagic flux is impaired in UVRAG-deficient mice has been shown. Given that autophagy regulates lipid metabolism, the role of UVRAG in fasting-induced hepatic steatosis was sought to determined. [Methods and results] Wild type (WT) and UVARG-deficient mice were subjected to normal conditions or 24 h fasting. In normal conditions, Oil red O staining showed no difference in hepatic lipid accumulation between WT and UVRAG-deficient mice. However, UVRAG deficiency exacerbates fasting-induced hepatic lipid accumulation compared with WT controls. Real time reverse transcription-polymerize chain reaction (RT-PCR) showed that UVRAG deficiency had no effects on the expression of lipid metabolic gene including CD 36, FAS, CPT-1, PPAR and FGF 21 in normal and fasting conditions. Sterol regulatory element-binding protein 1 (SREBP-1), which was lower in the liver from UVRAG-deficient mice, was comparable between fasted UVRAG-deficient mice and WT controls. Moreover, no difference in AMPK activity was observed in the liver from WT and UVRAG-deficient mice in fasting conditions. Plasma triglyceride and free fatty acid concentration were elevated in fed and fasted UVRAG-deficient mice compared with corresponding WT controls. Plasma cholesterol concentration was not different between WT and UVRAG-deficient mice in normal and fasting conditions. UVRAG deficiency exacerbated fasting-induced reduction in plasma glucose concentration. [Conclusions] UVRAG deficiency exacerbates fasting-induced hepatic steatosis, which may be due to impaired autophagic flux and increased uptake of plasma free fatty acid.

Key words: ultraviolet resistance-associated gene (UVRAG), fasting, autophagy, hepatic steatosis