title: Downregulating SOCS3 with siRNA ameliorates insulin signaling and glucose metabolism in hepatocytes of IUGR rats with catch-up growth.
abstract: BACKGROUND
  Individuals with intrauterine growth retardation (IUGR) who demonstrate a catch-up in body weight are prone to insulin resistance. High expressions of suppressor of cytokine signaling 3 (SOCS3) are thought to aggravate insulin resistance. We hypothesized that downregulating SOCS3 expression via small interfering RNA (siRNA) might have beneficial effects on insulin-resistant hepatocytes of catch-up growth IUGR rats (CG-IUGRs).
  
  
  METHODS
  An IUGR rat model was employed via maternal nutritional restriction. After evaluating metabolic states of CG-IUGR offspring, effective SOCS3-specific siRNA (siSOCS3) was transfected into cultured hepatocytes using liposomes. mRNA levels of SOCS3, insulin receptor substrates (IRSs), phosphatidylinositol 3-kinase (PI3K), and Akt2, key gluconeogenesis genes, were assessed via real-time PCR. Protein expression and phosphorylation changes were evaluated via western blot.
  
  
  RESULTS
  CG-IUGR hepatocytes showed increases in SOCS3 and gluconeogenic gene expressions, and decreases in IRS1 and PI3K expressions as compared with controls. After transfecting CG-IUGR hepatocytes with siSOCS3, protein levels of IRS1, PI3K, and phosphorylated Akt2 were higher as compared with those of untransfected CG-IUGR cells. Transcriptional suppression effects of gluconeogenesis genes were more obvious in siSOCS3-treated cells after insulin stimulation.
  
  
  CONCLUSIONS
  Additional insights were provided to understand mechanisms of insulin resistance in CG-IUGR rats. Downregulating SOCS3 might improve insulin signaling transduction and ameliorate hepatic glucose metabolism in insulin-resistant CG-IUGR rats in vitro.
authors.affiliation: Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Ye
authors.forename: Ruidan
authors.initials: R
authors.lastname: Zheng
authors.forename: Qun
authors.initials: Q
authors.lastname: Wang
authors.forename: Lihong
authors.initials: L
authors.lastname: Liao
authors.forename: Yanqin
authors.initials: Y
authors.lastname: Ying
authors.forename: Huiling
authors.initials: H
authors.lastname: Lu
authors.forename: Katherine
authors.initials: K
authors.lastname: Cianflone
authors.forename: Qin
authors.initials: Q
authors.lastname: Ning
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Luo
mesh_terms: D000818:Animals; D015536:Down-Regulation; D005317:Fetal Growth Retardation / Q000378:metabolism*; D005943:Gluconeogenesis / Q000235:genetics; D005947:Glucose / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D050356:Lipid Metabolism; D034741:RNA, Small Interfering / Q000235:genetics*; D051381:Rats; D015398:Signal Transduction; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics*
chemical_list: D007328:Insulin; D034741:RNA, Small Interfering; C491410:Socs3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D005947:Glucose