OBJECTIVE: The objective was to determine if physiological hyperglycemia induces a proatherogenic inflammatory response in mononuclear cells (MNCs) in obese reproductive-age women. RESEARCH METHODS AND PROCEDURES: Seven obese and 6 age-matched lean women (20 to 39 years of age) underwent a 2-hour 75-g oral glucose tolerance test. The release of interleukin-6 (IL-6) and interleukin-1beta (IL-1beta) from MNCs cultured in the presence of lipopolysaccharide (LPS) was measured after isolation from blood samples drawn fasting and 2 hours after glucose ingestion. Reactive oxygen species (ROS) generation and intra-nuclear nuclear factor kappaB (NFkappaB) from MNCs were quantified from the same blood samples. Insulin resistance was estimated by homeostasis model assessment of insulin resistance (HOMA-IR). Total body fat and truncal fat were determined by DXA. RESULTS: Obese women had a higher (p < 0.03) total body fat (42.2 +/- 1.1 vs. 27.7 +/- 2.0%), truncal fat (42.1 +/- 1.2 vs. 22.3 +/- 2.4%), and HOMA-IR (3.3 +/- 0.5 vs. 1.8 +/- 0.2). LPS-stimulated IL-6 release from MNCs was suppressed during hyperglycemia in lean subjects (1884 +/- 495 vs. 638 +/- 435 pg/mL, p < 0.05) but not in obese women (1184 +/- 387 vs. 1403 +/- 498 pg/mL). There was a difference (p < 0.05) between groups in the hyperglycemia-induced MNC-mediated release of IL-6 (-1196 +/- 475 vs. 219 +/- 175 pg/mL) and IL-1beta (-79 +/- 43 vs. 17 +/- 12 pg/mL). In addition, the obese group exhibited increased (p < 0.05) MNC-derived ROS generation (39.3 +/- 9.9 vs. -1.0 +/- 12.8%) and intra-nuclear NFkappaB (9.4 +/- 7.3 vs. -23.5 +/- 13.5%). Truncal fat was positively correlated with the MNC-derived IL-6 response (rho = 0.58, p < 0.05) and intra-nuclear NFkappaB (rho = 0.64, p < 0.05). DISCUSSION: These data suggest that obese reproductive-age women are unable to suppress proatherogenic inflammation during physiological hyperglycemia. Increased adiposity may be a significant contributor to this pro-inflammatory susceptibility.
OBJECTIVE: The objective was to determine if physiological hyperglycemia induces a proatherogenic inflammatory response in mononuclear cells (MNCs) in obese reproductive-age women. RESEARCH METHODS AND PROCEDURES: Seven obese and 6 age-matched lean women (20 to 39 years of age) underwent a 2-hour 75-g oral glucose tolerance test. The release of interleukin-6 (IL-6) and interleukin-1beta (IL-1beta) from MNCs cultured in the presence of lipopolysaccharide (LPS) was measured after isolation from blood samples drawn fasting and 2 hours after glucose ingestion. Reactive oxygen species (ROS) generation and intra-nuclear nuclear factor kappaB (NFkappaB) from MNCs were quantified from the same blood samples. Insulin resistance was estimated by homeostasis model assessment of insulin resistance (HOMA-IR). Total body fat and truncal fat were determined by DXA. RESULTS:Obesewomen had a higher (p < 0.03) total body fat (42.2 +/- 1.1 vs. 27.7 +/- 2.0%), truncal fat (42.1 +/- 1.2 vs. 22.3 +/- 2.4%), and HOMA-IR (3.3 +/- 0.5 vs. 1.8 +/- 0.2). LPS-stimulated IL-6 release from MNCs was suppressed during hyperglycemia in lean subjects (1884 +/- 495 vs. 638 +/- 435 pg/mL, p < 0.05) but not in obesewomen (1184 +/- 387 vs. 1403 +/- 498 pg/mL). There was a difference (p < 0.05) between groups in the hyperglycemia-induced MNC-mediated release of IL-6 (-1196 +/- 475 vs. 219 +/- 175 pg/mL) and IL-1beta (-79 +/- 43 vs. 17 +/- 12 pg/mL). In addition, the obese group exhibited increased (p < 0.05) MNC-derived ROS generation (39.3 +/- 9.9 vs. -1.0 +/- 12.8%) and intra-nuclear NFkappaB (9.4 +/- 7.3 vs. -23.5 +/- 13.5%). Truncal fat was positively correlated with the MNC-derived IL-6 response (rho = 0.58, p < 0.05) and intra-nuclear NFkappaB (rho = 0.64, p < 0.05). DISCUSSION: These data suggest that obese reproductive-age women are unable to suppress proatherogenic inflammation during physiological hyperglycemia. Increased adiposity may be a significant contributor to this pro-inflammatory susceptibility.
Authors: N Marui; M K Offermann; R Swerlick; C Kunsch; C A Rosen; M Ahmad; R W Alexander; R M Medford Journal: J Clin Invest Date: 1993-10 Impact factor: 14.808
Authors: Swathi Appachi; Karen R Kelly; Philip R Schauer; John P Kirwan; Stanley Hazen; Manjula Gupta; Sangeeta R Kashyap Journal: Obes Surg Date: 2011-12 Impact factor: 4.129
Authors: Frank González; K Sreekumaran Nair; Janice K Daniels; Eati Basal; Jill M Schimke Journal: Am J Physiol Endocrinol Metab Date: 2011-11-01 Impact factor: 4.310