Increased adipose tissue expression of hepcidin in severe obesity is independent from diabetes and NASH.
OBJECTIVE
Hepcidin is an acute-phase response peptide. We have investigated the possible involvement of hepcidin in massive obesity, a state of chronic low-grade inflammation. Three groups of severely obese patients with or without diabetes or nonalcoholic steatohepatitis were investigated.


METHODS
Hepcidin expression was studied in liver and adipose tissue of these patients. Hepcidin regulation was investigated in vitro by adipose tissue explant stimulation studies.


RESULTS
Hepcidin was expressed not only in the liver but also at the messenger RNA (mRNA) and the protein levels in adipose tissue. Moreover, mRNA expression was increased in adipose tissue of obese patients. The presence of diabetes or NASH did not modify the hepcidin expression levels in liver and adipose tissue. In adipose tissue, mRNA expression correlated with indexes of inflammation, interleukin-6, and C-reactive protein. Interleukin-6 also promoted in vitro hepcidin expression. A low transferrin saturation ratio was observed in 68% of the obese patients; moreover, 24% of these patients presented with anemia. The observed changes in iron status could be due to the role of hepcidin as a negative regulator of intestinal iron absorption and macrophage iron efflux. Interestingly, a feedback control mechanism on hepcidin expression related to low transferrin saturation occurred in the liver but not in the adipose tissue.


CONCLUSIONS
Hepcidin is a proinflammatory adipokine and may play an important role in hypoferremia of inflammation in obese condition.
Bekri
Soumeya
S
Laboratoire d'Hépato-Gastroentérologie, EA1186, Faculté Médecine de Nice, Nice, France. soumeya.bekri@chu-rouen.fr
Gual
Philippe
P
Anty
Rodolphe
R
Luciani
Nathalie
N
Dahman
Monsef
M
Ramesh
Bala
B
Iannelli
Antonio
A
Staccini-Myx
Aline
A
Casanova
Dominique
D
Ben Amor
Imed
I
Saint-Paul
Marie-Christine
MC
Huet
Pierre-Michel
PM
Sadoul
Jean-Louis
JL
Gugenheim
Jean
J
Srai
Surjit Kaila S
SK
Tran
Albert
A
Le Marchand-Brustel
Yannick
Y
D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis / Q000235:genetics*; D001706:Biopsy; D002097:C-Reactive Protein / Q000378:metabolism; D002460:Cell Line; D003920:Diabetes Mellitus / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005234:Fatty Liver / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D064451:Hepcidins; D006801:Humans; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009767:Obesity, Morbid / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D012720:Severity of Illness Index; D014168:Transferrin / Q000378:metabolism
D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; D064451:Hepcidins; D015850:Interleukin-6; D012333:RNA, Messenger; D014168:Transferrin; D002097:C-Reactive Protein