Evaluation of Fbxw7 expression and its correlation with expression of SREBP-1 in a mouse model of NAFLD

Abstract

The problems of aging, obesity and a number of types of metabolic syndromes, including diabetes, are associated with a higher risk of non-alcoholic fatty liver disease (NAFLD). However, the mechanisms of occurrence and development of NAFLD in humans remain unclear. Sterol regulatory element binding protein (SREBP)-1 is a transcription factor that is important in the development of NAFLD, which regulates the expression of lipogenic genes. SREBP-1 might be degraded through an F-box and WD repeat domain-containing 7 (Fbxw7)-dependent degradation. However, whether or not there is a correlation between Fbxw7 and SREBP-1 in NAFLD remains to be determined. The aim of this study was to investigate whether there was a reduction of Fbxw7 in NAFLD and an induced accumulation of SREBP-1 in a mouse model of NAFLD. Forty C57BL/6J mice were divided into control and HF groups and maintained on normal or high-fat (HF) diets. Following 8 weeks of treatment, the mice were sacrificed and assays of blood biomarkers typical of human NAFLD were performed. Liver samples were processed for histological examination. Fbxw7 mRNA expression was detected by reverse transcription-polymerase chain reaction (RT-PCR) and the protein expression of Fbxw7 and SREBP-1 was evaluated by immunohistochemistry and western blot analysis in the mouse liver tissues in the control and HF groups. The mRNA and protein expression of Fbxw7 was significantly decreased in the HF group compared with the control group (P<0.05, for both). In the HF group, the Fbxw7 protein expression was negatively correlated with SREBP-1 (r=-0.584; P<0.05). Fbxw7 was decreased in NAFLD and negatively correlated with SREBP-1, indicating that the Fbxw7-SREBP-1 axis may play a key pathological role in the development of NAFLD.