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Changes in Visceral Adipose Tissue Volume and Inflammatory Mediators Affect Insulin Sensitivity
Nana Gletsu, Edward Lin, Leena Khaitan, Bruce Ramshaw, Thomas R. Ziegler, Dimitris Papanicolaou, C. D. Smith, Emory University, Atlanta, GA

BACKGROUND:
Abdominal adipose tissue volume has been linked with insulin resistance and the production of inflammatory mediators such as interleukin (IL)-6 and C-reactive protein (CRP) by adipose tissue may be a causative factor. This study seeks to determine the influence of abdominal adiposity and the systemic levels of IL-6 and CRP on insulin metabolism following surgery-induced weight loss.

METHODS:
Severely obese individuals (N=10) undergoing Roux-en-Y gastric bypass (RYGB) were evaluated in the General Clinical Research Center at baseline and 6 mos following surgery. Insulin sensitivity (Si) was determined by IVGTT at the same time points. Changes in visceral adipose tissue (VIS) volume was quantified by computed tomography. Plasma IL-6 and CRP were measured by ELISA. VIS contribution to the production of adipokines was confirmed in separate experiments by omental biopsies obtained from severely obese (N = 8) and lean patients (N = 16) undergoing abdominal surgery. Linear correlation analysis was used to determine associations between Si and other outcome variables. Results are reported as mean SEM, significance if p < 0.05.

RESULTS:
Systemic IL-6 levels were higher in severely obese patients than in lean patients at baseline (4.1 0.3 pg/ml vs. 1.9 0.4 pg/ml). VIS IL-6 content in biopsies obtained from obese patients was also significantly higher than those obtained from lean patients (11.09 1.57 pg/mg vs. 3.38 0.35 pg/mg). In patients undergoing RYGB, body mass index was reduced from 48.3 0.9 kg/m2 to 36.3 1.0 kg/m2, (p < 0.0001) at 6 mos. Compared with baseline, total body fat mass and VIS volume were reduced by 39.0 1.9 % and 45.5 4.4 %, respectively, (both p < 0.0001). These changes were accompanied by a marked improvement in insulin sensitivity of 78.3 12.3%. Negative longitudinal correlations were found between Si and CRP at 6 mo (r = -0.87, p = 0.001).

CONCLUSIONS:
Visceral adipose tissue contributes to the production of systemic inflammatory mediators and longitudinal changes in systemic concentrations of inflammatory mediators closely predict insulin action in vivo. These novel findings offer additional insights that link obesity and insulin resistance via the activity of inflammatory mediators.


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