title: Hemojuvelin: a new link between obesity and iron homeostasis.
abstract: The adipose tissue may play an active role in systemic iron regulation and this role may be determinant in obese patients. Indeed, we reported previously that hepcidin, the iron-regulatory hormone, is expressed in adipose tissue and its messenger RNA (mRNA) expression is increased in adipose tissue of morbidly obese patients. The objectives of this study were to characterize the status of hemojuvelin (HJV), another iron-regulatory protein, within the adipose tissue of morbidly obese patients. Since cell-associated HJV acts as a coreceptor of bone morphogenetic protein (BMP) to enhance hepcidin expression in liver cells, we investigated the possible involvement of this pathway in adipose tissue in regulating hepcidin expression. HJV expression was studied in adipose tissue of morbidly obese patients. Soluble HJV blood concentrations were assessed. Hepcidin regulation through BMP pathway was investigated in cultured adipocytes. HJV was expressed both at mRNA and protein levels in adipose tissue. Moreover, its mRNA expression was highly increased in adipose tissue of obese patients and correlated with mRNA hepcidin expression levels. Interestingly, HJV expressed by adipose tissue may be effective since cultured adipocytes increased their hepcidin expression when challenged with BMP2 through Smad effectors. In addition, blood concentrations of soluble HJV were significantly increased. In conclusion, adipose tissue may influence iron homeostasis in obese patients by expressing major iron-regulatory proteins and the BMP signaling pathway could be involved in regulating hepcidin expression in this tissue.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U895, Team 8, Hepatic Complications in Obesity, Nice, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Luciani
authors.forename: Carole
authors.initials: C
authors.lastname: Brasse-Lagnel
authors.forename: Maura
authors.initials: M
authors.lastname: Poli
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Anty
authors.forename: Celine
authors.initials: C
authors.lastname: Lesueur
authors.forename: Mireille
authors.initials: M
authors.lastname: Cormont
authors.forename: Annie
authors.initials: A
authors.lastname: Laquerriere
authors.forename: Vanessa
authors.initials: V
authors.lastname: Folope
authors.forename: Yannick
authors.initials: Y
authors.lastname: LeMarchand-Brustel
authors.forename: Jean
authors.initials: J
authors.lastname: Gugenheim
authors.forename: Philippe
authors.initials: P
authors.lastname: Gual
authors.forename: Albert
authors.initials: A
authors.lastname: Tran
authors.forename: Soumeya
authors.initials: S
authors.lastname: Bekri
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism*; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D006706:Homeostasis; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D035925:Iron-Regulatory Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000378:metabolism; D009767:Obesity, Morbid / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D023181:Antimicrobial Cationic Peptides; D051017:Apoptosis Regulatory Proteins; D019485:Bone Morphogenetic Proteins; C412403:DIABLO protein, human; D058851:GPI-Linked Proteins; C578702:HAMP protein, human; C481006:HJV protein, human; C579599:Hamp protein, mouse; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D047908:Intracellular Signaling Peptides and Proteins; D035925:Iron-Regulatory Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D007501:Iron