Sterol Regulatory Element Binding Protein 2 Overexpression Is Associated With Reduced Adipogenesis and Ectopic Fat Accumulation in Transgenic Spontaneously Hypertensive Rats
It has been reported that the major function of the sterol regulatory element binding protein 2 (SREBP-2) is to activate preferentially cholesterol biosynthesis in liver and adipose tissue rather than fatty acid synthesis. In the current study, we analyzed the effects of overexpression of human dominant-positive SREBP-2 transgene under control of PEPCK promoter in the spontaneously hypertensive rat (SHR) on lipid and glucose metabolism. Transgenic overexpression of SREBP-2 was associated with significantly higher hepatic triglycerides (20.4±0.9 vs. 17.0±0.05 µmol/g, P<0.05) but not cholesterol (10.6±0.4 vs. 10.9±0.4 µmol/g) and decreased relative weight of epididymal fat pad (0.73±0.03 vs. 0.830.03, P<0.05). In addition, muscle triglyceride (15.8±3.7 vs. 8.5±1.2 µmol/g, P<0.001) and cholesterol (3.6±0.5 vs. 2.1±0.1 µmol/g, P<0.05) concentrations were significantly increased in transgenic rats when compared to SHR controls. Ectopic fat accumulation was associated with significantly increased serum glucose levels (6.4±0.1 vs. 5.9±0.1 mmol/l, P<0.005) and reduced insulin levels (1.78±0.33 vs. 2.73±0.37 nmol/l, P<0.05) in transgenic rats. These results provide evidence for important role of SREBP-2 in regulation of lipid and glucose metabolism.