 
         
         
         Abstract
         
         Obesity is associated with an increased risk of developing insulin resistance, Type
            2 diabetes, and cardiovascular disease. Reports have suggested that adipose tissue-derived
            cytokines such as tumor necrosis factor-α, interleukin-6 and interleukin-8 could be
            involved in the development of these health complications. Since estrogen has been
            suggested to attenuate the development of atherosclerosis and cardiovascular disease,
            we investigated whether ovariectomy affected the production and release of these three
            adipose tissue-derived cytokines with and without estrogen replacement in vivo and in vitro. Female Wistar rats were submitted to either a) ovariectomy, b) ovariectomy and estrogen
            replacement, or c) sham operation. After five months, animals were sacrificed and
            parametrial adipose tissue was removed and incubated for up to 24 hours with either
            interleukin-1β (IL-1β) (5 µg/l), dexamethasone (50 nM) or estrogen (50 nM). Ovariectomy
            significantly increased interleukin-6 gene expression (p < 0.05) as well as interleukin-8
            protein levels (p < 0.05) and gene expression (p < 0.05) in the adipose tissue, and
            estrogen replacement significantly reversed this increase (p < 0.05). However, no
            direct effects of estrogen were found in in vitro adipose tissue incubations. Neither ovariectomy nor estrogen replacement had any
            effects on tumor necrosis factor-α protein levels or gene expression. In conclusion,
            estrogen-deficient rats were found to have increased production of interleukin-6 and
            interleukin-8, which could be attenuated by estrogen-replacement. Since estrogen is
            suggested to be anti-atherosclerotic, this effect might be caused by a reduction in
            cytokine production from the adipose tissue.
         
         
         
            
Key words
         
         
            Interleukin-6 - Interleukin-8 - Tumor Necrosis Factor-α - Rodent Adipose Tissue -
               Estrogen - Obesity - Atherosclerosis
          
      
    
   
      
         
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J. M. Bruun, M.D.
            Department of Endocrinology and Metabolism
            
            Aarhus Amtssygehus · Tage Hansensgade 2 · 8000 Aarhus C · Denmark
            
            Fax: + 4589497649
            
            Email: jmb@mail-online.dk