title: Activation of nuclear factor kappa B pathway and reduction of hypothalamic oxytocin following hypothalamic lesions.
abstract: BACKGROUND
  Hypothalamic obesity (HO) occurs in patients with tumors and lesions in the medial hypothalamic region. In this study, a hyperphagic rat model of combined medial hypothalamic lesions (CMHL) was used to test which specific inflammatory molecules are involved.
  
  
  METHODS
  In order to target specific homeostatic medial hypothalamic nuclei (arcuate, ventromedial, and dorsomedial nuclei), male Sprague-Dawley rats (age of 8 weeks, ~250 g body weight) received four electrolytic lesions or sham surgery. Post-surgery food intake and weight changes were tracked and hypothalamic gene expression for inflammatory molecules as well as anorexigenic peptide oxytocin 7 days and 7 months post-surgery were tested.
  
  
  RESULTS
  Seven days post-surgery, average food intake increased by 23%, and body weight gain had increased by 68%. Toll-like 4 receptor/nuclear factor-κB (TLR4/NF-κB)-pathway was specifically activated in the mediobasal hypothalamus (MBH), resulting in 3-fold higher tumor necrosis factor (TNF)-α, 10-fold higher interleukin (IL) 1-β mRNA levels, and higher expression of suppression of cytokine signaling (SOCS) 3, while oxytocin mRNA levels were significantly reduced in CMHL rats versus sham surgery rats 7 days post-surgery. At 7 months, inflammation was less stimulated in MBH of CMHL rats compared to 7 days post-surgery and SOCS 3 as well as oxytocin mRNA levels were comparable between the two groups.
  
  
  CONCLUSIONS
  Medial hypothalamic lesions are associated with strong post-surgery hyperphagia and activation of TLR4/NF-κB-pathway as well as reduced expression of oxytocin in the hypothalamus.
authors: Division of Endocrinology, Department of Pediatrics, University of Washington, USA; Center for Integrative Brain Research, Seattle Children's Research Institute, USA.
authors: Christian L
authors: CL
authors: Roth
authors: Center for Integrative Brain Research, Seattle Children's Research Institute, USA.
authors: Gabrielle
authors: G
authors: D'Ambrosio
authors: Center for Integrative Brain Research, Seattle Children's Research Institute, USA.
authors: Clinton
authors: C
authors: Elfers
keywords: hyperphagia; hypothalamic lesion; inflammation; nuclear factor kappa B; obesity; oxytocin