An alternatively spliced soluble TNF-alpha receptor is associated with metabolic disorders: a replication study.
In a previous study, we identified a biologically active form of tumor necrosis factor-alpha receptor 2 (sTNFR2) produced by differential splicing (DS-TNFR2) which antagonized TNF-alpha biological activity. Obesity, insulin resistance and type 2 diabetes are linked to increased TNF-alpha action. We hypothesized that subjects with detectable DS-TNFR2 would be protected from developing obesity and related metabolic disorders. Thus, we investigated if circulating DS-TNFR2 concentration was associated with components of the so-called metabolic syndrome among 269 consecutive subjects from the general population. DS-TNFR2 was measured using a monoclonal antibody against an epitope present in TNFR2 (first 14 residues of the juxtamembrane region) but predicted to be absent in soluble proteolytic cleavage-produced TNFR2. Plasma DS-TNFR2 concentration was significantly decreased among patients with glucose intolerance or type 2 diabetes mellitus (p=0.026). DS-TNFR2 tended to be associated with fasting and post-load glucose (both r=-0.11, p=0.054), and with diastolic blood pressure in men (r=-0.16, p=0.07). Serum DS-TNFR2 concentration was significantly associated with LDL cholesterol (r=-0.28, p=0.002), uric acid (r=-0.13, p=0.04) and with blood glycated hemoglobin (r=-0.13, p=0.04). DS-TNFR2 declined with increased number of components of the metabolic syndrome (p=0.03). Those subjects with 2 or more components had significantly decreased circulating DS-TNFR2 levels (0.96+/-2.2 versus 1.7+/-3.2, p=0.033). In summary, the circulating concentration of DS-TNFR2 seems to be inversely linked to metabolic disorders, hinting at a possible anti-inflammatory role.
Fernández-Real
José Manuel
JM
Unit of Diabetes, Endocrinology and Nutrition, University Hospital of Girona "Dr. Josep Trueta", Ctra. França s/n, 17007 Girona, Spain. uden.jmfernandezreal@htrueta.scs.es
Botas-Cervero
Patricia
P
Lainez
Begoña
B
Ricart
Wifredo
W
Delgado
Elías
E
D000328:Adult; D000368:Aged; D017398:Alternative Splicing; D008078:Cholesterol, LDL / Q000097:blood; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000209:etiology / Q000235:genetics*; D005260:Female; D018149:Glucose Intolerance / Q000097:blood / Q000209:etiology / Q000235:genetics*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D020033:Protein Isoforms; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood / Q000235:genetics*
D008078:Cholesterol, LDL; D020033:Protein Isoforms; D047889:Receptors, Tumor Necrosis Factor, Type II