Location: Location not imported yet.Title: Subcutaneous adipose tissue from obese and lean adults does not release hepcidin, in vivo) Author
|Tussing Humphreys, Lisa|
Submitted to: The Scientific World
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/23/2011
Publication Date: 11/1/2011
Citation: Tussing Humphreys, L.M., Frayn, K.N., Smith, S.R., Westerman, M., Dennis, L., Nemeth, E., Thomson, J.L., Pusatcioglu, C. 2011. Subcutaneous adipose tissue from obese and lean adults does not release hepcidin, in vivo. The Scientific World. 11:2191-206. Interpretive Summary: Obesity is associated with iron deficiency. Hepcidin is a protein in the body that controls iron status. Elevated hepcidin decreases the activity of the body’s sole iron exporter, ferroportin-1. Reduced ferroporitn-1 activity limits dietary iron absorption, and traps iron in storage sites making iron less available for use by the body. Several researchers have shown that blood levels of hepcidin are significantly elevated in the obese, compared to lean women and children, suggesting that hepcidin may play a role in the iron deficiency observed in obesity. Interestingly, fat tissue also produces hepcidin, and levels have been shown to be higher in the adipose tissue of obese compared to lean women. This discovery led to the hypothesis that the low iron status and increased blood levels of hepcidin observed in obese individuals is, in part, a result of the large amount of fat tissue present in obesity, releasing hepcidin into circulation; however, to date, no studies have demonstrated that fat tissue in humans secretes hepcidin into the blood stream. We determined if subcutaneous fat tissue located in the abdomen secretes hepcidin into circulation by measuring the amount of hepcidin in blood sampled from a vein draining the adipose tissue, and in blood sampled from an hand vein, and if the amount of hepcidin secreted by the fat tissue was modified by obesity. If the amount of hepcidin measured in the fat tissue vein is greater than in the hand vein, hepcidin is being released from the adipose tissue. Our findings show that the abdominal subcutaneous adipose tissue from obese or lean individuals does not secrete hepcidin into circulation. This suggests that subcutaneous adipose tissue has little impact on whole-body iron metabolism or circulating hepcidin concentrations in humans. This information will greatly benefit nutrition and medical researchers as they try to unravel the mystery of obesity-related iron deficiency. Gaining an understanding of the relationship between obesity and diminished iron status and possible causes of this condition, in light of the burgeoning obesity epidemic, is critical since the health impact of suffering simultaneously from both conditions remains unknown.
Technical Abstract: Hepcidin is a small peptide that functions as the both the main regulator of systemic iron homeostasis, and as the link between host defense and iron metabolism. Elevated hepcidin is associated with reduced iron bioavailability, while low hepcidin concentrations are associated with increased dietary iron absorption and mobilization from body iron stores. Hepcidin is primarily produced by the liver, but is also expressed in other periphery tissues, including adipose tissue (AT). Obesity is associated with both elevated hepcidin concentrations and iron depletion, with some suggesting that the exaggerated fat mass in obesity could contribute significantly to circulating hepcidin levels, consequently, altering iron homeostasis. To date, there is no data illustrating in vivo release of hepcidin from human AT or if differences in secretion exist between obese and lean individuals. The objective of this study was to determine if abdominal subcutaneous AT (AbScAT) releases hepcidin in vivo, and if released, is modified by obesity. Arterio-venous differences were measured across AbScAT in 9 obese (Body Mass Index (BMI) > 30 kg/m2) and 9 lean (BMI 18.5-24.9 kg/m2) fasted adults. A superficial epigastric vein draining AbScAT, and an arterialized dorsal hand vein were cannulated, and blood samples taken simultaneously from the two sites. Plasma was analyzed for hepcidin using a c-ELISA. BMI and waist circumference (WC) were also assessed. Overall (n=18), plasma hepcidin concentrations were significantly higher in arterialized compared to AbScAT venous samples [mean arterio-venous difference (paired-t) = 4.9 ± 9.6 nmol/l, p= 0.04]. When differences in arterialized and venous plasma hepcidin concentrations were assessed by group (Obese and Lean separately), venous concentrations were again lower than arterialized, but these differences failed to reach statistical significance. Net regional hepcidin release was not calculated overall or by group because mean venous plasma hepcidin concentrations were lower than mean arterialized plasma concentrations, indicating no net hepcidin release. Additionally, significant correlations between AbScAT venous and arterialized plasma hepcidin concentrations, with anthropometric variables, were not observed. In conclusion, although AbScAT expresses hepcidin, findings from this vein drainage study suggest there is no net release from this AT depot, and thereby does not have systemic impact on iron metabolism.