title: Soluble TNF-alpha receptor 2 produced by alternative splicing is paradoxically associated with markers of liver injury.
abstract: Tumor necrosis factor-alpha and insulin resistance play central roles in the pathogenesis of abnormal hepatocellular function. We evaluate the relationship between a novel serum DS-TNFR2 (an alternatively spliced soluble TNF-alpha receptor 2) isoform and parameters of liver health. Serum ALT, AST and GGT, insulin resistance, adiponectin and DS-TNFR2 isoform concentrations were measured in 492 subjects from two different Caucasian Spanish populations. We found a significant negative association between serum ALT and DS-TNFR2 levels in both populations (r=-0.269; p=0.002 and r=-0.152; p=0.01, respectively). DS-TNFR2 levels also correlated negatively with serum AST (r=-0.142; p=0.042) and GGT (r=-0.206; p=0.003) in population 1 and with AST (r=-0.127; p=0.038) in population 2. In multiple regression analysis models, serum DS-TNFR2 was shown to be an independent modulator of serum ALT activity after adjusting for sex, age, BMI, HOMA and adiponectin in both populations. These results suggest potential anti-inflammatory properties of this TNF-alpha receptor 2 isoform at the hepatic level.
authors.affiliation: Unit of Diabetes, Endocrinology and Nutrition, Hospital de Girona Dr Josep Trueta, Ctra. França s/n, 17007 Girona, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Esteve
authors.forename: Patricia
authors.initials: P
authors.lastname: Botas
authors.forename: Elías
authors.initials: E
authors.lastname: Delgado
authors.forename: Abel
authors.initials: A
authors.lastname: López-Bermejo
authors.forename: Begoña
authors.initials: B
authors.lastname: Lainez
authors.forename: Pablo
authors.initials: P
authors.lastname: Engel
authors.forename: Wifredo
authors.initials: W
authors.lastname: Ricart
authors.forename: Jose-Manuel
authors.initials: JM
authors.lastname: Fernández-Real
mesh_terms: D052242:Adiponectin / Q000097:blood / Q000235:genetics; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D017398:Alternative Splicing; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics / Q000276:immunology; D008099:Liver / Q000276:immunology* / Q000293:injuries*; D008297:Male; D008875:Middle Aged; D020033:Protein Isoforms / Q000097:blood / Q000235:genetics; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood* / Q000235:genetics* / Q000276:immunology; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D052242:Adiponectin; D015415:Biomarkers; D020033:Protein Isoforms; D047889:Receptors, Tumor Necrosis Factor, Type II; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase