title: Hypoxia-mimetic effects in the secretome of human preadipocytes and adipocytes.
abstract: White adipose tissue (WAT) regulates energy metabolism by secretion of proteins with endocrine and paracrine effects. Dysregulation of the secretome of obesity-associated enlarged WAT may lead to obesity-related disorders. This can be caused by hypoxia as a result of poorly vascularized WAT. The effect of hypoxia on the secretome of human (pre)adipocytes is largely unknown. Therefore, we investigated the effect of CoCl2, a hypoxia mimetic, on the secretome of human SGBS (pre)adipocytes by a proteomics approach combined with bioinformatic analysis. In addition, regulation of protein secretion was examined by protein turnover experiments. As such, secretome changes were particularly associated with protein down-regulation and extracellular matrix protein dysregulation. The observed up-regulation of collagens in adipocytes may be essential for cell survival while down-regulation of collagens in preadipocytes may indicate a disturbed differentiation process. These CoCl2-induced changes reflect WAT dysfunction that ultimately may lead to obesity-associated complications. In addition, 9 novel adipocyte secreted proteins were identified from which 6 were regulated by CoCl2. Mass spectrometry data have been deposited to the ProteomeXchange with identifier PXD000162.
authors.affiliation: NUTRIM School for Nutrition, Toxicology and Metabolism, Department of Human Biology, Maastricht University, Maastricht, The Netherlands. Electronic address: a.rosenow@maastrichtuniversity.nl.
authors.forename: Anja
authors.initials: A
authors.lastname: Rosenow
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Noben
authors.forename: Freek G
authors.initials: FG
authors.lastname: Bouwman
authors.forename: Edwin C M
authors.initials: EC
authors.lastname: Mariman
authors.forename: Johan
authors.initials: J
authors.lastname: Renes
mesh_terms: D052438:Adipocytes, White / Q000166:cytology / Q000378:metabolism*; D016587:Antimutagenic Agents / Q000494:pharmacology*; D015687:Cell Hypoxia / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003035:Cobalt / Q000494:pharmacology*; D006801:Humans; D020543:Proteome / Q000378:metabolism*; D055571:Secretory Pathway / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D016587:Antimutagenic Agents; D020543:Proteome; D003035:Cobalt; C018021:cobaltous chloride
keywords: ECM; Extracellular matrix; HIF; Human (pre)adipocyte; Hypoxia-mimetic; SGBS; Secretome; Simpson Golabi Behmel Syndrome; TG; Turnover; WAT; hypoxia-induced factor; triglycerides; white adipose tissue