title: Lentiviral vector-mediated knockdown of SOCS3 in the hypothalamus protects against the development of diet-induced obesity in rats.
abstract: OBJECTIVE
  Leptin resistance is a feature of most cases of obesity in both humans and rodents. The suppressor of cytokine signalling 3 (SOCS3) is a negative-feedback regulator of leptin signalling involved in leptin resistance; therefore, the suppression of SOCS3 is a potential therapy for leptin resistance in obesity. In the studies, we investigated whether hypothalamic silencing of SOCS3 would attenuate diet-induced obesity in rats.
  
  
  METHODS
  First we established hypothalamic SOCS3-deficient rats through lentiviral vector (LV)-mediated RNA interference (RNAi) technique, then provided a high-fat diet or a chow diet to the rats. After 8 weeks of the diet, the serum leptin and insulin concentrations were measured by RIA, and the gene expressions of SOCS3 and the long form of leptin receptor in hypothalamus were detected by a real time RT-PCR. The leptin-induced Stat3 activation was examined by Western blot.
  
  
  RESULTS
  The RNAi protocol specifically knocked down the expression of SOCS3 mRNA by 50% approximately. The rats treated with LV-SOCS3-shRNA exhibited enhanced leptin-induced Stat3 activation, decreased body weight gain and improved metabolic parameters when exposed to a high-fat diet.
  
  
  CONCLUSIONS
  Our results provide evidence that the rats treated with hypothalamic SOCS3 silencing are significantly protected against the development of diet-induced obesity and SOCS3 is a potential target molecule for therapeutic intervention of obesity.
authors.affiliation: Department of Pediatrics, The Second Affiliated Hospital of Dalian Medical University, Dalian, China. liuzj_1963@yahoo.com.cn
authors.forename: Z-J
authors.initials: ZJ
authors.lastname: Liu
authors.forename: J
authors.initials: J
authors.lastname: Bian
authors.forename: Y-L
authors.initials: YL
authors.lastname: Zhao
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: N
authors.initials: N
authors.lastname: Zou
authors.forename: D
authors.initials: D
authors.lastname: Li
mesh_terms: D000818:Animals; D004041:Dietary Fats / Q000494:pharmacology*; D020868:Gene Silencing; D005822:Genetic Vectors; D007031:Hypothalamus / Q000378:metabolism*; D007150:Immunohistochemistry; D016086:Lentivirus; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D009765:Obesity / Q000378:metabolism / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000009:adverse effects* / Q000235:genetics
chemical_list: D004041:Dietary Fats; D020738:Leptin; C491410:Socs3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins