title: Altered tumor necrosis factor alpha release from mononuclear cells of obese reproductive-age women during hyperglycemia.
abstract: 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 alpha 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-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-alpha 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-alpha 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 hyperglycemia in obese women, and this response may contribute to impaired glucose disposal and insulin resistance.
authors.affiliation: Department of Reproductive Biology, Case Western Reserve University School of Medicine, Cleveland, OH 44109, USA. fgonzalez@metrohealth.org
authors.forename: Frank
authors.initials: F
authors.lastname: González
authors.forename: Judi
authors.initials: J
authors.lastname: Minium
authors.forename: Neal S
authors.initials: NS
authors.lastname: Rote
authors.forename: John P
authors.initials: JP
authors.lastname: Kirwan
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D006943:Hyperglycemia / Q000097:blood*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D016014:Linear Models; D008070:Lipopolysaccharides / Q000494:pharmacology; D009765:Obesity / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein