title: Erythropoietin does not activate erythropoietin receptor signaling or lipolytic pathways in human subcutaneous white adipose tissue in vivo.
abstract: BACKGROUND
  Erythropoietin (Epo) exerts direct effects on white adipose tissue (WAT) in mice in addition to its erythropoietic effects, and in humans Epo increases resting energy expenditure and affect serum lipid levels, but direct effects of Epo in human WAT have not been documented. We therefore investigated the effects of acute and prolonged Epo exposure on human WAT in vivo.
  
  
  METHODS
  Data were obtained from two clinical trials: 1) acute Epo exposure (rHuEpo, 400 IU/kg) followed by WAT biopsies after 1 h and 2) 10 weeks treatment with the erythropoiesis-stimulating agent (ESA) Darbepoietin-alpha. Biopsies were analyzed by PCR for Epo receptor (Epo-R) mRNA. A new and highly specific antibody (A82, Amgen) was used to evaluate the presence of Epo-R by western blot analysis in addition to Epo-R signaling proteins (Akt, STAT5, p70s6k, LYN, and p38MAPK), activation of lipolytic pathways (ATGL, HSL, CGI-58, G0S2, Perilipin, Cidea, Cidec, AMPK, and ACC), and mitochondrial biogenesis (VDAC, HSP90, PDH, and SDHA).
  
  
  RESULTS
  No evidence of in vivo activation of the Epo-R in WAT could be documented despite detectable levels of Epo-R mRNA.
  
  
  CONCLUSIONS
  Thus, in contradiction to animal studies, Epo treatment within a physiological relevant range in humans does not exert direct effects in a subcutaneous WAT.
authors.affiliation: Department of Endocrinology and Internal Medicine, NBG/THG, Aarhus University Hospital, Nørrebrogade 44, 8000, Aarhus C, Denmark. brittchr@hotmail.com.|Research Laboratory for Biochemical Pathology, Institute for Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark. brittchr@hotmail.com.
authors.forename: Britt
authors.initials: B
authors.lastname: Christensen
authors.affiliation: Department of Endocrinology and Internal Medicine, NBG/THG, Aarhus University Hospital, Nørrebrogade 44, 8000, Aarhus C, Denmark.
authors.forename: Birgitte
authors.initials: B
authors.lastname: Nellemann
authors.affiliation: Department of Endocrinology and Internal Medicine, NBG/THG, Aarhus University Hospital, Nørrebrogade 44, 8000, Aarhus C, Denmark.
authors.forename: Jens Otto L
authors.initials: JO
authors.lastname: Jørgensen
authors.affiliation: Department of Endocrinology and Internal Medicine, NBG/THG, Aarhus University Hospital, Nørrebrogade 44, 8000, Aarhus C, Denmark.
authors.forename: Steen B
authors.initials: SB
authors.lastname: Pedersen
authors.affiliation: Research Laboratory for Biochemical Pathology, Institute for Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark.|Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Jessen
mesh_terms: D052436:Adipose Tissue, White / Q000187:drug effects* / Q000378:metabolism; D001706:Biopsy; D002986:Clinical Trials as Topic; D004921:Erythropoietin / Q000008:administration & dosage* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D008066:Lipolysis / Q000235:genetics; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D017467:Receptors, Erythropoietin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D050151:Subcutaneous Fat / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D017467:Receptors, Erythropoietin; D004921:Erythropoietin
keywords: Darbepoietin-α; Lipolysis; Mitochondria; rHuEpo