Elevated systemic hepcidin and iron depletion in obese premenopausal females.
Hepcidin, the body's main regulator of systemic iron homeostasis, is upregulated in response to inflammation and is thought to play a role in the manifestation of iron deficiency (ID) observed in obese populations. We determined systemic hepcidin levels and its association with body mass, inflammation, erythropoiesis, and iron status in premenopausal obese and nonobese women (n = 20/group) matched for hemoglobin (Hb). The obese participants also had liver and abdominal visceral and subcutaneous adipose tissue assessed for tissue iron accumulation and hepcidin mRNA expression. Despite similar Hb levels, the obese women had significantly higher serum hepcidin (88.02 vs. 9.70 ng/ml; P < 0.0001) and serum transferrin receptor (sTfR) (P = 0.001) compared to nonobese. In the obese women hepcidin was not correlated with serum iron (r = -0.02), transferrin saturation (Tsat) (r = 0.17) or sTfR (r = -0.12); in the nonobese it was significantly positively correlated with Tsat (r = 0.70) and serum iron (r = 0.58), and inversely with sTfR (r = -0.63). Detectable iron accumulation in the liver and abdominal adipose tissue of the obese women was minimal. Liver hepcidin mRNA expression was ~700 times greater than adipose tissue production and highly correlated with circulating hepcidin levels (r = 0.61). Serum hepcidin is elevated in obese women despite iron depletion, suggesting that it is responding to inflammation rather than iron status. The source of excess hepcidin appears to be the liver and not adipose tissue. The ID of obesity is predominantly a condition of a true body iron deficit rather than maldistribution of iron due to inflammation. However, these findings suggest inflammation may perpetuate this condition by hepcidin-mediated inhibition of dietary iron absorption.
Tussing-Humphreys
Lisa M
LM
Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, Illinois, USA.
Nemeth
Elizabeta
E
Fantuzzi
Giamila
G
Freels
Sally
S
Guzman
Grace
G
Holterman
Ai-Xuan L
AX
Braunschweig
Carol
C
D050153:Abdominal Fat / Q000378:metabolism; D000328:Adult; D018798:Anemia, Iron-Deficiency / Q000453:epidemiology* / Q000276:immunology / Q000378:metabolism; D023181:Antimicrobial Cationic Peptides / Q000097:blood / Q000235:genetics*; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D064451:Hepcidins; D006801:Humans; D007249:Inflammation / Q000453:epidemiology* / Q000378:metabolism; D007408:Intestinal Absorption / Q000502:physiology; D019266:Iron, Dietary / Q000097:blood; D008099:Liver / Q000378:metabolism; D009043:Motor Activity; D015999:Multivariate Analysis; D009765:Obesity / Q000453:epidemiology* / Q000276:immunology / Q000378:metabolism; D011237:Predictive Value of Tests; D017697:Premenopause / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014168:Transferrin / Q000378:metabolism
D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; D006454:Hemoglobins; D064451:Hepcidins; D019266:Iron, Dietary; D012333:RNA, Messenger; D014168:Transferrin