Obese reproductive-age women exhibit a proatherogenic inflammatory response during hyperglycemia.
OBJECTIVE
The objective was to determine if physiological hyperglycemia induces a proatherogenic inflammatory response in mononuclear cells (MNCs) in obese reproductive-age women.


METHODS
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).


CONCLUSIONS
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.
González
Frank
F
Department of Obstetrics and Gynecology, Mayo Clinic College of Medicine, Charlton 3-117, 200 First Street SW, Rochester, MN 55905, USA. gonzalez.frank@mayo.edu
Rote
Neal S
NS
Minium
Judi
J
O'leary
Valerie B
VB
Kirwan
John P
JP
D050154:Adiposity; D000328:Adult; D050197:Atherosclerosis / Q000276:immunology*; D001823:Body Composition; D002097:C-Reactive Protein / Q000032:analysis / Q000378:metabolism; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D006943:Hyperglycemia / Q000150:complications*; D018836:Inflammation Mediators / Q000032:analysis / Q000378:metabolism*; D007333:Insulin Resistance; D053583:Interleukin-1beta / Q000032:analysis / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D016328:NF-kappa B / Q000097:blood / Q000378:metabolism; D009765:Obesity / Q000150:complications*; D017382:Reactive Oxygen Species / Q000097:blood / Q000378:metabolism; D012098:Reproduction
D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D002097:C-Reactive Protein