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This Article Full Text Full Text (PDF) All Versions of this Article: 293/1/E102    most recent 00089.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Lo, J. Articles by Grinspoon, S. K. Search for Related Content PubMed PubMed Citation Articles by Lo, J. Articles by Grinspoon, S. K.

Effects of TNF- neutralization on adipocytokines and skeletal muscle adiposity in the metabolic syndrome

¹Program in Nutritional Metabolism and ²Division of Musculoskeletal Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; ³Division of Endocrinology, Children's Hospital of Philadelphia, Philadelphia; and ⁴Division of Endocrinology, Diabetes, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

Submitted 6 February 2007 ; accepted in final form 14 March 2007

In a prior study, we have shown that tumor necrosis factor (TNF)- neutralization improves inflammatory markers and total adiponectin in patients with the metabolic syndrome, without improving insulin sensitivity. In this study, we sought to extend our understanding of the effects of TNF- neutralization in this human model of obesity by investigating the responses of high-molecular-weight (HMW) adiponectin, resistin, leptin, and muscle adiposity to etanercept in patients with the metabolic syndrome. Fifty-six men and women with the metabolic syndrome enrolled in a double-blind randomized placebo-controlled trial. Circulating concentrations of total and HMW adiponectin, resistin, and leptin were determined at baseline and after 4 wk of treatment with etanercept. Muscle adiposity was measured by computed tomography (CT). Although etanercept increased total adiponectin concentration, the HMW form, which is thought to mediate insulin sensitivity, was 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, P = 0.02). Resistin tended to decrease in the etanercept-treated group compared with placebo (–0.6 ± 0.7 vs. 1.2 ± 0.7 ng/ml, P = 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, P = 0.04], suggesting an increase in muscle adiposity. Together, these results demonstrate 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.

tumor necrosis factor-; adiponectin; resistin; muscle adiposity; metabolic syndrome