Altered tumor necrosis factor α release from mononuclear cells of obese reproductive-age women during hyperglycemia

The aim of the study was to determine whether lipopolysaccharide (LPS)-stimulated tumor necrosis factor alpha (TNF-alpha) release from mononuclear cells (MNCs) is altered in obese reproductive-age women in response to hyperglycemia. Six obese and 8 age-matched normal-weight women (18-40 years) underwent a 2-hour 75-g oral glucose tolerance test. Tumor necrosis factor g release was measured from MNCs cultured in the presence of LPS after isolation from blood samples drawn fasting and 2 hours after glucose ingestion. Insulin resistance was derived by homeostasis model assessment of insulin resistance. Total body fat (%) and truncal fat (%) were determined by dual-energy absorptiometry. Obese women had a higher (P <.03) body mass index (34.1 +/- 1.1 vs 21.9 +/- 0.8 kg/m(2)), percentage of total body fat (42.4% +/- 1.3% vs 28.7% +/- 1.8%), and percentage of truncal fat (42.1% +/- 1.2% vs 24.7% +/- 2.2%). Homeostasis model assessment of insulin resistance was greater in the obese group (58.0 +/- 10.6 vs 27.8 +/- 4.3, P <.02). Fasting plasma C-reactive protein (7787 +/- 884 vs 236 79 ng/mL, P <.0001) and TNF-alpha (2.37 +/- 0.09 vs 0.54 +/- 0.04 pg/mL, P <.05) were both elevated in obese women. Hyperglycemia resulted in a suppression of LPS-stimulated TNF-alpha release from MNCs of normal-weight subjects (154 +/- 21 vs 57 +/- 28 pg/mL, P <.003), but no change in obese women (148 +/- 36 vs 173 +/- 49 pg/mL). The TNF-a response was different between groups (-97 +/- 21 vs +24 22 pg/mL, P <.003). There was also a positive association between the incremental change in MNC-derived TNF-a and percentage of truncal fat (r = 0.75, P <.002). In conclusion, these data suggest that there is an absence of the "normal", suppression of TNF-alpha in MNCs after hyperglyemia in obese women, and this response may contribute to impaired glucose disposal and insulin resistance. (c) 2006 Elsevier Inc. All rights reserved.