DIETARY, PHYSIOLOGICAL, GENETIC, AND BEHAVIORAL PREDICTORS OF WEIGHT GAIN IN A HEALTHY, YOUNG, ETHNICALLY-MIXED POPULATION
Location: Food Processing and Sensory Quality Research
Title: Elevated systemic hepcidin and iron depletion in obese pre-menopausal females.
| Tussing Humphreys, Lisa |
| Nemeth, Elizabeth - |
| Fantuzzi, Giamila - |
| Freels, Sally - |
| Guzman, Grace - |
| Holterman, Ai-Xuan - |
| Braunschweig, Carol - |
Submitted to: Obesity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: August 6, 2009
Publication Date: July 1, 2010
Citation: Tussing Humphreys, L.M., Nemeth, E., Fantuzzi, G., Freels, S., Guzman, G., Holterman, A., Braunschweig, C. 2010. Elevated systemic hepcidin and iron depletion in obese pre-menopausal females. Obesity. PMID:19816411.
Interpretive Summary: Obesity is associated with an increased rate of iron deficiency despite adequate dietary iron intake. The cause of this deficiency is poorly understood. Hepcidin, the body’s main regulator of iron balance, is simultaneously controlled by three pathways: inflammation (increases hepcidin), increased rate of red blood cell production (decreases hepcidin), and anemia (decreases hepcidin). 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. Obesity is a low-grade inflammatory condition, therefore, we proposed to link hepcidin to iron deficiency in obese individuals. We compared serum hepcidin, iron status, inflammation, and rate of red blood cell production in 40 pre-menopausal obese and non-obese women. The obese participants also had liver and fat tissue assessed for iron storage. Serum hepcidin was significantly higher in the obese women despite poorer iron status, compared to the non-obese women, suggesting that hepcidin was predominately regulated by inflammation rather than iron status. Surprisingly, fat and liver tissue iron stores were low in the obese women despite elevated hepcidin. Our findings suggest the level of hepcidin observed in the obese women was too low to decrease ferroportin-1 activity at body storage sites, but high enough to decrease ferroportin-1 activity at the small intestine, blocking dietary iron absorption; therefore, dietary iron sources, although adequate, may be poorly absorbed by obese individuals. Inadequate dietary iron absorption would result in depleted iron stores, and ultimately iron deficiency, as daily body iron losses exceed dietary iron repletion. This information will greatly benefit nutrition researchers and public health professionals who determine and establish nutritional guidelines for americans.
Hepcidin, the body’s main regulator of systemic iron homeostasis, is unregulated 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 pre-menopausal obese and non-obese women (n=20/group) matched for hemoglobin. The obese participants also had liver and abdominal visceral, and subcutaneous adipose tissue assessed for tissue iron accumulation and hepcidin mRNA expression. Despite similar hemoglobin levels, the obese women had significantly higher serum hepcidin [88.02 vs. 9.70 ng/ml; p<.0001], and serum transferring receptor (p= 0.001) compared to non-obese. In the obese women hepcidin was not correlated with serum iron(r= -0.02), Tsat(r= 0.17) or sTfR(r= -0.12); in the non-obese 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.