title: Early onset inflammation in pre-insulin-resistant diet-induced obese rats does not affect the vasoreactivity of isolated small mesenteric arteries.
abstract: BACKGROUND
  Obesity is an increasing burden affecting developed and emerging societies since it is associated with an increased risk of diabetes and consequent cardiovascular complications. Increasing evidence points towards a pivotal role of inflammation in the etiology of vascular dysfunction. Our study aimed to investigate signs of inflammation and their relation to vascular dysfunction in rats receiving a high fat diet.
  
  
  METHODS
  Diet-induced obese (DIO) rats were used as a model since these rats exhibit a human pre-diabetic pathology. Oral glucose and insulin tolerance tests were conducted on DIO rats and their controls prior to the development of insulin resistance. Furthermore, the plasma contents of selected cytokines [macrophage chemoattractant protein (MCP-1), interleukin-6 (IL-6), and interleukin-1 (IL-1)] and the concentration of adiponectin were measured. Using wire myography, we tested the vascular function of isolated small mesenteric arteries.
  
  
  RESULTS
  DIO animals had significantly (p < 0.05) increased body weight (721.2 ± 6.3 g) compared to age- and sex-matched controls (643.4 ± 14.6 g), as well as a significant increase (p < 0.01) in body fat percentage (29.7 ± 1.7% and 22.7 ± 0.97%, respectively). No significant difference in fasting plasma insulin levels could be detected between the two groups (chow-fed group 141.5 ± 15.1 pmol/l; high fat-fed group 125.9 ± 18.8 pmol/l). However, the levels of MCP-1 (89.7 ± 4.2 pg/ml vs. 60.8 ± 7.7 pg/ml) and IL-6 (61.6 ± 3.1 pg/ml vs. 41.6 ± 7.4 pg/ml) were significantly elevated in DIO animals (p < 0.05) as compared to controls. Adiponectin levels were also significantly increased (p < 0.01) in DIO rats (10.8 ± 0.7 ng/ml) versus controls (6.9 ± 0.5 ng/ml). No difference in vascular or endothelial function was evident as determined by responses to acetylcholine, sodium nitroprusside, endothelin-1, and calcitonin gene-related peptide.
  
  
  CONCLUSIONS
  In DIO rats, which have not yet developed hyperinsulinaemia or glucose intolerance, the levels of inflammatory mediators MCP-1 and Il-6 are significantly increased without concomitant vascular dysfunction. The results show that inflammation and obesity are tightly associated, and that inflammation is manifested prior to significant insulin resistance and vascular dysfunction.
authors: Hagedorn Research Institute, Novo Nordisk, Gentofte, Denmark. mmb@farma.ku.dk
authors: Martin
authors: M
authors: Blædel
authors: Kirsten
authors: K
authors: Raun
authors: Harrie C M
authors: HC
authors: Boonen
authors: Majid
authors: M
authors: Sheykhzade
authors: Anette
authors: A
authors: Sams
mesh_terms: D054392:Adipokines / Q000097:blood; D000818:Animals; D018925:Chemokines / Q000097:blood; D016207:Cytokines / Q000097:blood; D004041:Dietary Fats / Q000008:administration & dosage; D066298:In Vitro Techniques; D007249:Inflammation / Q000209:etiology*; D007333:Insulin Resistance; D008297:Male; D008638:Mesenteric Arteries / Q000503:physiopathology*; D009765:Obesity / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D054392:Adipokines; D018925:Chemokines; D016207:Cytokines; D004041:Dietary Fats