González Frank, Minium Judi, Rote Neal S, Kirwan John P
Department of Reproductive Biology, Case Western Reserve University School of Medicine, Cleveland, OH 44109, USA.
Metabolism. 2006 Feb;55(2):271-6. doi: 10.1016/j.metabol.2005.08.022.
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.
本研究的目的是确定肥胖育龄女性单核细胞（MNCs）中脂多糖（LPS）刺激的肿瘤坏死因子α（TNF-α）释放对高血糖的反应是否发生改变。6名肥胖和8名年龄匹配的正常体重女性（18 - 40岁）接受了2小时的75克口服葡萄糖耐量试验。在空腹采血及葡萄糖摄入2小时后从血样中分离出MNCs，在LPS存在的情况下培养MNCs，测量TNF-α释放量。胰岛素抵抗通过稳态模型评估胰岛素抵抗来推导。通过双能吸收法测定全身脂肪（%）和躯干脂肪（%）。肥胖女性的体重指数更高（P < 0.03）（34.1±1.1 vs 21.9±0.8 kg/m2）、全身脂肪百分比（42.4%±1.3% vs 28.7%±1.8%）和躯干脂肪百分比（42.1%±1.2% vs 24.7%±2.2%）。肥胖组的稳态模型评估胰岛素抵抗更高（58.0±10.6 vs 27.8±4.3，P < 0.02）。肥胖女性空腹血浆C反应蛋白（7787±884 vs 236±79 ng/mL，P < 0.0001）和TNF-α（2.37±0.09 vs 0.54±0.04 pg/mL，P < 0.05）均升高。高血糖导致正常体重受试者的MNCs中LPS刺激的TNF-α释放受到抑制（154±21 vs 57±28 pg/mL，P < 0.003），但肥胖女性无变化（148±36 vs 173±49 pg/mL）。两组之间的TNF-α反应不同（-97±21 vs +24±22 pg/mL，P < 0.003）。MNCs衍生的TNF-α的增量变化与躯干脂肪百分比之间也存在正相关（r = 0.75，P < 0.002）。总之，这些数据表明肥胖女性高血糖后MNCs中不存在TNF-α的“正常”抑制，这种反应可能导致葡萄糖处置受损和胰岛素抵抗。
