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

Frank González, Judi Minium, Neal S. Rote, John P. Kirwan

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

The aim of the study was to determine whether lipopolysaccharide (LPS)-stimulated tumor necrosis factor α (TNF-α) 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 α 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/m2), 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-α (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-α 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-α 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-α 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-α in MNCs after hyperglycemia in obese women, and this response may contribute to impaired glucose disposal and insulin resistance.

Original languageEnglish (US)
Pages (from-to)271-276
Number of pages6
JournalMetabolism: Clinical and Experimental
Volume55
Issue number2
DOIs
StatePublished - Feb 1 2006

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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