Effects of TNF-α neutralization on adipocytokines and skeletal muscle adiposity in the metabolic syndrome
- 1 July 2007
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Endocrinology and Metabolism
- Vol. 293 (1), E102-E109
- https://doi.org/10.1152/ajpendo.00089.2007
Abstract
In a prior study, we have shown that tumor necrosis factor (TNF)-α 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-α 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-α 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-α neutralization in obesity.Keywords
This publication has 61 references indexed in Scilit:
- Effects of Etanercept in Patients With the Metabolic SyndromeArchives of Internal Medicine, 2006
- Effects of Pioglitazone on Lipoproteins, Inflammatory Markers, and Adipokines in Nondiabetic Patients with Metabolic SyndromeArteriosclerosis, Thrombosis, and Vascular Biology, 2006
- Effects of infliximab treatment on insulin resistance in patients with rheumatoid arthritis and ankylosing spondylitisAnnals Of The Rheumatic Diseases, 2005
- Impaired Mitochondrial Activity in the Insulin-Resistant Offspring of Patients with Type 2 DiabetesNew England Journal of Medicine, 2004
- Impaired Multimerization of Human Adiponectin Mutants Associated with DiabetesJournal of Biological Chemistry, 2003
- Hormonal Regulation of Adiponectin Gene Expression in 3T3-L1 AdipocytesBiochemical and Biophysical Research Communications, 2002
- Tumor Necrosis Factor α Is a Negative Regulator of Resistin Gene Expression and Secretion in 3T3-L1 AdipocytesBiochemical and Biophysical Research Communications, 2001
- Role of AMP-activated protein kinase in mechanism of metformin actionJCI Insight, 2001
- The expression of tumor necrosis factor in human adipose tissue. Regulation by obesity, weight loss, and relationship to lipoprotein lipase.JCI Insight, 1995
- Reduced tyrosine kinase activity of the insulin receptor in obesity-diabetes. Central role of tumor necrosis factor-alpha.JCI Insight, 1994