Activation of nuclear factor kappa B pathway and reduction of hypothalamic oxytocin following hypothalamic lesions.
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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-?B (TLR4/NF-?B)-pathway was specifically activated in the mediobasal hypothalamus (MBH), resulting in 3-fold higher tumor necrosis factor (TNF)-?, 10-fold higher interleukin (IL) 1-? 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. CONCLUSION:Medial hypothalamic lesions are associated with strong post-surgery hyperphagia and activation of TLR4/NF-?B-pathway as well as reduced expression of oxytocin in the hypothalamus.
SUBMITTER: Roth CL
PROVIDER: S-EPMC4976786 | biostudies-literature | 2016 Feb
REPOSITORIES: biostudies-literature
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