Signal Transducers and Activators of Transcription


1991;88:9292C9296. and after 4 wk of treatment with etanercept. Muscles adiposity was assessed by computed tomography (CT). Although etanercept increased total adiponectin concentration, the HMW form, which is thought to mediate insulin sensitivity, was TH-302 (Evofosfamide) unchanged. Thus the ratio of HMW to total adiponectin decreased following etanercept treatment compared with placebo (?0.03 0.03 vs. 0.06 0.03, = 0.02). Resistin tended to decrease in the etanercept-treated group compared with placebo (?0.6 0.7 vs. 1.2 0.7 TH-302 (Evofosfamide) ng/ml, = 0.06), whereas leptin was not altered. Etanercept decreased muscle attenuation on CT [?0.61 0.64 Hounsfield units (HU) vs. 1.54 0.77 HU in placebo, = 0.04], suggesting an increase TH-302 (Evofosfamide) in muscle adiposity. Together, these results demonstrate AKT that neutralization of TNF- in obese humans results in differential effects on critical adipokines and body composition indexes. These findings may help to explain the lack of effect on insulin sensitivity and extend our knowledge of the biological effects of TNF- neutralization in obesity. = 0.74 and <0.0001). The ratio of HMW to total adiponectin has previously been termed the adiponectin sensitivity index (38). Sandwich enzyme immunoassay technique was used to measure TNF- (CV 5.3C 8.8%; sensitivity 0.12 pg/ml), soluble TNF- receptor (sTNFR) 1 (CV 3.6 C5.0%; sensitivity 0.001 ng/ml), and sTNFR2 (CV 2.6 C 4.8%; sensitivity 0.001 ng/ml; R&D Systems, Minneapolis, MN). Resistin and leptin were measured using ELISA kits from Linco Research (St. Charles, MO; CV 3.7C 6.5% and TH-302 (Evofosfamide) sensitivity 0.1 ng/ml for resistin; CV 3.5C5.8% and sensitivity 0.5 ng/ml for leptin; see Ref. 41). Body composition and muscle attenuation by CT scan Weight was determined in the morning, before breakfast. A cross-sectional CT scan at the level of the L4 pedicle was performed to determine abdominal subcutaneous and visceral fat areas (SAT and VAT, respectively). A single 1-cm slice CT through the left midfemur was also performed, equidistant between the articular surfaces of femoral head and medial femoral condyle. Scan parameters for each image were standardized (144 cm table height, 80 kV, 70 mA, 2 s, 1.0 cm slice thickness, 48 cm field of view). Fat attenuation coefficients were set at ?50 to ?250 Hounsfield units (HU; see Ref. 5). The cross-sectional area and mean attenuation values in HU of the whole leg, the anterior muscles, and the posterior muscles were assessed using commercial software (Alice; Parexel, Waltham, MA) TH-302 (Evofosfamide) by manually tracing the anterior and posterior thigh muscle compartments. The mean leg muscle attenuation was calculated by taking the average of the anterior and posterior muscle attenuation values. The CV for the measurement of muscle attenuation in our radiology department is 2.4% (9). Total fat was measured by dual energy X-ray absorptiometry (DEXA; Hologic, Waltham, MA) with a precision error of 1 1.7% for fat in our laboratory. Statistical analysis Students were imputed with the use of the last-observation-carried forward method. Results are reported as means SE unless otherwise indicated. All reported values are two-sided, and all statistical analyses were performed using SAS JMP statistics software version 5.1. (SAS Institute, Cary, NC). RESULTS Characteristics of study participants At baseline, the age of the study participants was 45.6 1.1 (SE) yr, and BMI was 36.5 0.7 (SE) kg/m2. Thirty participants were male and 26 were female; 37 were Caucasian, 17 were Black, and 2 were Hispanic. Baseline values for glucose, insulin, HOMA-IR, leptin, resistin, total adiponectin, HMW adiponectin, %HMW to total adiponectin, leg muscle attenuation, VAT, SAT, total body fat, and lean body mass are shown in Table 1. These measurements were similar at baseline between the placebo and etanercept-treated groups. In the group randomized to receive etanercept, two subjects discontinued intervention after baseline treatment. In the placebo group, one subject discontinued before completion of the baseline visit, and one discontinued intervention after baseline.