title: Induction of heme-oxygenase-1 (HO-1) does not enhance adiponectin production in human adipocytes: Evidence against a direct HO-1 - Adiponectin axis.
abstract: Adiponectin is a salutary adipokine and hypoadiponectinemia is implicated in the aetiology of obesity-related inflammation and cardiometabolic disease making therapeutic strategies to increase adiponectin attractive. Emerging evidence, predominantly from preclinical studies, suggests induction of heme-oxygenase-1 (HO-1) increases adiponectin production and reduces inflammatory tone. Here, we aimed to test whether induction of HO-1 enhanced adiponectin production from mature adipocytes. Treatment of human adipocytes with cobalt protoporphyrin (CoPP) or hemin for 24-48 h increased HO-1 expression and activity without affecting adiponectin expression and secretion. Treatment of adipocytes with TNFα reduced adiponectin secretion and increased expression and secretion of additional pro-inflammatory cytokines, IL-6 and MCP-1, as well as expression of sXBP-1, a marker of ER stress. HO-1 induction failed to reverse these effects. These results demonstrate that induction of HO-1 does not directly enhance adiponectin production or ameliorate the pro-inflammatory effects of TNFα and argue against a direct HO-1 - adiponectin axis.
authors.affiliation: Mater Research Institute-UQ, Translational Research Institute, Brisbane, QLD, Australia.
authors.forename: Mengliu
authors.initials: M
authors.lastname: Yang
authors.affiliation: Mater Research Institute-UQ, Translational Research Institute, Brisbane, QLD, Australia; Faculty of Pharmacy, Keio University, Tokyo, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Kimura
authors.affiliation: Mater Research Institute-UQ, Translational Research Institute, Brisbane, QLD, Australia.
authors.forename: Choaping
authors.initials: C
authors.lastname: Ng
authors.affiliation: Mater Research Institute-UQ, Translational Research Institute, Brisbane, QLD, Australia.
authors.forename: Jingjing
authors.initials: J
authors.lastname: He
authors.affiliation: Mater Research Institute-UQ, Translational Research Institute, Brisbane, QLD, Australia.
authors.forename: Sahar
authors.initials: S
authors.lastname: Keshvari
authors.affiliation: Mater Research Institute-UQ, Translational Research Institute, Brisbane, QLD, Australia.
authors.forename: Felicity J
authors.initials: FJ
authors.lastname: Rose
authors.affiliation: Mater Research Institute-UQ, Translational Research Institute, Brisbane, QLD, Australia.
authors.forename: Johanna L
authors.initials: JL
authors.lastname: Barclay
authors.affiliation: Mater Research Institute-UQ, Translational Research Institute, Brisbane, QLD, Australia. Electronic address: jon.whitehead@mater.uq.edu.au.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Whitehead
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D052242:Adiponectin / Q000096:biosynthesis*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects / Q000502:physiology; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D011524:Protoporphyrins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; C111835:CCL2 protein, human; D018932:Chemokine CCL2; C508600:IL6 protein, human; D015850:Interleukin-6; D011524:Protoporphyrins; D014409:Tumor Necrosis Factor-alpha; C007095:cobaltiprotoporphyrin; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1
keywords: Adiponectin; HO-1; Inflammation; Therapeutic