Early onset inflammation in pre-insulin-resistant diet-induced obese rats does not affect the vasoreactivity of isolated small mesenteric arteries

摘要

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. Conclusion: 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.