Abstract
Objective To investigate whether hypothalamic silencing of suppressor of cytokine signaling 3( SOCS3 ) by RNA interference ( RNAi ) attenuates diet-induced obesity and leptin resistance in rats.Methods Hypothalamic SOCS3-deficient rats were established by means of lentiviral vector ( LV ) mediated RNAi technique,and then were fed with a high-fat diet for 8 weeks.After the rats were sacrificed,the serum leptin and insulin concentrations were measured by RIA, and the expression of SOCS3 in hypothalamus was detected by immunohistochemistry and realtime PCR.Results The immunostaining showed that SOCS3 protein expression was significantly reduced and the expression of SOCS3 mRNA was decreased by 49％ in SOCS3 RNAi group compared to the controls( P＜0.01 ).The rats with hypothalamic SOCS3 knockdown exhibited a significant hampering in gaining body weight with lowered concentrations of leptin[ ( 8.18±2.10 vs 10.85±2.23 ) ng/ml ],insulin[ ( 18.89±4.88 vs 26.78±6.01 )mU/L],glucose [ (4.89±0.91 vs 6.26± 1.41 )mmol/L] and triglyceride [ (0.47 ±0.10 vs 0.62 ±0.16)mmol/L] when exposed to a high-fat diet(P＜0.05 or P＜0.01 ).Conclusion The results provide evidence that rats with hypothalamic SOCS3 silencing by RNAi are resistant to diet-induced obesity,leptin resistance,and metabolic disorder. Key words: Lentiviral ; Suppressor of cytokine signaling 3 ; RNAi ; Hypothalamus ; Obesity
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