Obese reproductive-age women exhibit a proatherogenic inflammatory response during hyperglycemia

Frank González, Neal S. Rote, Judi Minium, Vaalerie B. O'Leary, John P. Kirwan

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Objective: The objective was to determine if physiological hyperglycemia induces a proatherogenic inflammatory response in mononuclear cells (MNCs) in obese reproductiveage 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-lß (IL-Iß) 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 KB (NFKB) 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 hyperglycemiainduced MNC-mediated release of IL-6 (-1196 ± 475 vs. 219 ± 175 pg/mL) and IL-1ß (-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 NFKB (9.4 ± 7.3 vs. -23.5 ± 13.5%). Truncal fat was positively correlated with the MNC-derived IL-6 response (p = 0.58, p < 0.05) and intra-nuclear NFKB (p = 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.

Original languageEnglish (US)
Pages (from-to)2436-2444
Number of pages9
JournalObesity
Volume15
Issue number10
DOIs
StatePublished - Oct 1 2007

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Keywords

  • Abdominal adiposity
  • Atherosclerosis
  • Hyperglycemia
  • Inflammation

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Nutrition and Dietetics

Cite this

González, F., Rote, N. S., Minium, J., O'Leary, V. B., & Kirwan, J. P. (2007). Obese reproductive-age women exhibit a proatherogenic inflammatory response during hyperglycemia. Obesity, 15(10), 2436-2444. https://doi.org/10.1038/oby.2007.289