title: Adipocyte C1QTNF5 expression is BMI-dependently related to early adipose tissue dysfunction and systemic CTRP5 serum levels in obese children.
abstract: The recently identified adipocytokine C1QTNF5 (encodes for CTRP5) has been demonstrated to inhibit pro-metabolic insulin signaling in adipocytes. We hypothesized that adipocyte C1QTNF5 expression in subcutaneous (sc) adipose tissue (AT) would correlate with the degree of obesity, systemic CTRP5 serum levels, and early AT and metabolic dysfunction in children.
  
  
  
  Sc AT samples were obtained from 33 healthy Caucasian lean children aged 10.06±4.84 years and 42 overweight and obese children aged 13.34±3.12 years. C1QTNF5 expression in sc AT as well as in investigated cell lines was assessed by quantitative real-time PCR. Systemic CTRP5 levels were assessed by ELISA.
  
  
  
  C1QTNF5 expression in sc adipocytes increased with body mass index (BMI) standard deviation score (SDS; R=0.48, P<0.001), body fat percentage (R=0.4, P=0.004), adipocyte number (R=0.69, P<0.001) and systemic CTRP5 serum levels (R=0.28, P=0.025) whereas expression in the stromal vascular fraction (SVF) was inversely correlated with BMI SDS (R=-0.24, P=0.04). Multiple regression analysis confirmed that BMI SDS was the strongest independent predictor for C1QTNF5 expression in sc adipocytes. SVF C1QTNF5 levels strongly correlated with SVF CD31 expression (R=0.54, P<0.001) indicating expression by endothelial cells. Primary human endothelial cells demonstrated stronger expression compared with human Simpson-Golahbi-Behmel syndrome pre-adipocytes and adipocytes. Adipocyte C1QTNF5 expression levels were BMI-dependently related to fasting insulin (R=0.3, P=0.03) and leptin serum levels (R=0.5, P<0.001). Sc AT samples containing crown-like structures (CLS) demonstrated increased adipocyte C1QTNF5 expression compared to CLS-negative samples (P=0.03). Functionally, tumor necrosis factor (TNF)α caused a fourfold induction of C1QTNF5 in human adipocytes (P<0.001) and a 50% reduction in primary human endothelial cells (P<0.001).
  
  
  
  In children adipocyte C1QTNF5 expression is already strongly related to the degree of obesity and is associated with obesity-related AT alterations, systemic CTRP5 serum levels as well as circulating markers of metabolic disease and is positively regulated by TNFα in vitro.
authors.affiliation: Department of Women's and Child Health, Center for Pediatric Research Leipzig (CPL), University Hospital for Children &Adolescents, University of Leipzig, Leipzig, Germany.
authors.forename: J T
authors.initials: JT
authors.lastname: Schwartze
authors.affiliation: Department of Women's and Child Health, Center for Pediatric Research Leipzig (CPL), University Hospital for Children &Adolescents, University of Leipzig, Leipzig, Germany.|Medical Faculty, Medical Center AdiposityDiseases (IFB), University of Leipzig, Leipzig, Germany.
authors.forename: K
authors.identifier: 0000-0002-6878-6033
authors.initials: K
authors.lastname: Landgraf
authors.affiliation: Medical Faculty, Medical Center AdiposityDiseases (IFB), University of Leipzig, Leipzig, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Spielau
authors.affiliation: Department of Women's and Child Health, Center for Pediatric Research Leipzig (CPL), University Hospital for Children &Adolescents, University of Leipzig, Leipzig, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Rockstroh
authors.affiliation: Department of Women's and Child Health, Center for Pediatric Research Leipzig (CPL), University Hospital for Children &Adolescents, University of Leipzig, Leipzig, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Löffler
authors.affiliation: Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University of Leipzig, Leipzig, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Kratzsch
authors.affiliation: Department of Women's and Child Health, Center for Pediatric Research Leipzig (CPL), University Hospital for Children &Adolescents, University of Leipzig, Leipzig, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Kiess
authors.affiliation: Department of Women's and Child Health, Center for Pediatric Research Leipzig (CPL), University Hospital for Children &Adolescents, University of Leipzig, Leipzig, Germany.|Medical Faculty, Medical Center AdiposityDiseases (IFB), University of Leipzig, Leipzig, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Körner
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000293:Adolescent; D000367:Age Factors; D015992:Body Mass Index; D002460:Cell Line; D002648:Child; D003094:Collagen / Q000097:blood* / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology; D008297:Male; D063766:Pediatric Obesity / Q000097:blood* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D060888:Real-Time Polymerase Chain Reaction; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000502:physiology; D050151:Subcutaneous Fat / Q000166:cytology*; D013851:Thinness / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000502:physiology
chemical_list: C487851:C1QTNF5 protein, human; D007328:Insulin; D003094:Collagen