Down-regulation of suppressor of cytokine signaling 3 expression in hypothalamus attenuates high-fat dietinduced obesity in rats
10.3760/cma.j.issn.1000-6699.2012.01.019
- VernacularTitle:细胞因子信号转导抑制因子3表达下调抵抗高脂饮食诱导肥胖的作用机制研究
- Author:
Xuemei BAI
;
Zhengjuan LIU
;
Yuchuan WANG
;
Li ZHANG
- Publication Type:Journal Article
- Keywords:
Lentiviral;
Suppressor of cytokine signaling 3;
RNAi;
Hypothalamus;
Obesity
- From:
Chinese Journal of Endocrinology and Metabolism
2012;28(1):63-67
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo 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 measuredbyRIA, andthe expressionof SOCS3inhypothalamus was detectedby immunohistochemistry and realtime PCR.ResultsThe 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 ).ConclusionThe results provide evidence that rats with hypothalamic SOCS3 silencing by RNAi are resistant to diet-induced obesity,leptin resistance,and metabolic disorder.