title: Elevated endothelin-1 (ET-1) levels may contribute to hypoadiponectinemia in childhood obesity.
abstract: BACKGROUND
  Pediatric obesity is associated with endothelial dysfunction and hypoadiponectinemia, but the relationship between these two conditions remains to be fully clarified. Whether enhanced release of endothelin-1 (ET-1) may directly impair adiponectin (Ad) production in obese children is not known.
  
  
  OBJECTIVE
  The aim of the study was to explore whether and how high circulating levels of ET-1 may contribute to impair Ad production, release, and vascular activity.
  
  
  METHODS
  Sixty children were included into obese (Ob; n = 30), overweight (OW; n = 11), and lean (n = 19) groups. Total and high-molecular-weight Ad, ET-1, vascular cell adhesion molecule-1, and von Willebrand factor levels were measured in serum samples. Adipocytes were stimulated with exogenous ET-1 or with sera from lean, OW, and Ob, and Ad production and release measured in the absence or in the presence of ETA (BQ-123) and ETB (BQ-788) receptor blockers, p42/44 MAPK inhibitor PD-98059, or c-Jun NH2-terminal protein kinase inhibitor SP-600125. Vasodilation to Ad was evaluated in rat isolated arteries in the absence or in the presence of BQ-123/788.
  
  
  RESULTS
  Total and high-molecular-weight Ad was significantly decreased and ET-1 levels significantly increased in OW (P < .01) and Ob (P < .001) children. A statistically significant linear regression (P < .01) was found between Ad and ET-1. Exposure of adipocytes to exogenous ET-1 or serum from OW and Ob significantly decreased Ad mRNA and protein levels (P < 0.001). The inhibitory effect of ET-1 on Ad was reverted by BQ-123/788 or PD-98059 but not SP-600125. Ad-mediated vasodilation was further increased in arteries pretreated with BQ-123/788.
  
  
  CONCLUSIONS
  ET-1-mediated inhibition of Ad synthesis via p42/44 MAPK signaling may provide a possible explanation for hypoadiponectinemia in pediatric obesity and contribute to the development of cardiovascular complications.
authors: Department of Biomedical Sciences and Human Oncology, University of Bari, Medical School, 70124 Bari, Italy.
authors: Carmela
authors: C
authors: Nacci
authors: Valentina
authors: V
authors: Leo
authors: Leonarda
authors: L
authors: De Benedictis
authors: Maria Rosaria
authors: MR
authors: Carratù
authors: Nicola
authors: N
authors: Bartolomeo
authors: Maria
authors: M
authors: Altomare
authors: Paola
authors: P
authors: Giordano
authors: Maria Felicia
authors: MF
authors: Faienza
authors: Monica
authors: M
authors: Montagnani
mesh_terms: D041721:3T3-L1 Cells; D052242:Adiponectin / Q000097:blood / Q000172:deficiency / Q000378:metabolism; D017668:Age of Onset; D000818:Animals; D002648:Child; D019332:Endothelin-1 / Q000097:blood* / Q000378:metabolism; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D008661:Metabolism, Inborn Errors / Q000097:blood* / Q000209:etiology* / Q000378:metabolism; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism / Q000502:physiology; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism / Q000502:physiology; D009765:Obesity / Q000097:blood* / Q000150:complications* / Q000453:epidemiology; D050177:Overweight / Q000097:blood / Q000150:complications / Q000453:epidemiology; D051381:Rats; D017208:Rats, Wistar; D013851:Thinness / Q000097:blood / Q000150:complications / Q000453:epidemiology
chemical_list: D052242:Adiponectin; D019332:Endothelin-1; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3