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Title: Decreased serum hepcidin, inflammation, and improved functional iron status six-months post-restrictive bariatric surgery.

Author
item Tussing Humphreys, Lisa
item NEMETH, ELIZABETA - Geffen School Of Medicine
item FANTUZZI, GIAMILA - University Of Illinois
item FREELS, SALLY - University Of Illinois
item HOLTERMAN, AI-XUAN - Rush University Medical Center
item GALVANI, CARLOS - University Of Illinois
item AYLOO, SUBHASHINI - University Of Illinois
item VITELLO, JOSEPH - University Of Illinois
item BRAUNSCHWEIG, CAROL - University Of Illinois

Submitted to: Obesity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/9/2009
Publication Date: 1/14/2010
Citation: Tussing Humphreys, L.M., Nemeth, E., Fantuzzi, G., Freels, S., Holterman, A., Galvani, C., Ayloo, S., Vitello, J., Braunschweig, C. 2010. Decreased serum hepcidin, inflammation, and improved functional iron status six-months post-restrictive bariatric surgery. Obesity. PMID:20075851.

Interpretive Summary: Obesity is associated with iron deficiency. Poor iron status in obese individuals is thought to be linked to low-grade chronic inflammation, and inflammation-triggered production of the iron regulating protein hepcidin, and not inadequate dietary iron intake. Elevated hepcidin can cause iron deficiency and poor replenishment of body iron stores by preventing adequate absorption of dietary iron into the body. Elevated hepcidin can accomplish this by shutting down the body’s sole iron exporter, ferroportin-1, which is located on cells in the small intestine. Weight loss is associated with decreased inflammation, however, the impact of weight reduction and decreased inflammation on hepcidin production and iron status in obese individuals is unknown. We determined the impact of weight loss on iron status, serum hepcidin, inflammation, and dietary iron intake in 20 obese, pre-menopausal women before and six months after weight loss surgery. At baseline, the presence of iron deficiency was high with 45% of the women having poor iron status. Six months after surgery, women lost a significant amount of weight, were less inflamed, and had significantly lower hepcidin, along with improved iron status. No significant difference in dietary iron was noted after surgery. Weight loss and related reduction in inflammation and hepcidin likely allows for enhanced dietary iron absorption leading to improved iron status. Findings from this study are important because they help nutrition researchers and health professionals better understand the link between obesity and iron deficiency.

Technical Abstract: Excess adiposity is associated with low-grade inflammation and decreased iron status. Iron depletion (ID) in obesity is thought to be mediated by an inflammation-induced increase in the body’s main regulator of iron homeostasis, hepcidin. Elevated hepcidin can result in ID as it prevents the release of dietary iron absorbed into the enterocytes, limiting replenishment of body iron losses. Weight reduction is associated with decreased inflammation, however, the impact of reduced inflammation on iron status and systemic hepcidin in obese individuals remains unknown. We determined, prospectively, the impact of weight loss on iron status, serum hepcidin, inflammation, and dietary iron intake in 20 obese pre-menopausal females six months post-restrictive bariatric surgery. At baseline, the presence of ID was high with 45% of the women having serum transferrin receptor (sTfR) >28.1 nmol/L. Differences between baseline and 6-month post-surgery for BMI(47.56 vs. 39.55 kg/m2; p<.0001), CRP(10.83 vs. 5.71 mg/L; p<.0001), sTfR(29.97 vs. 23.08 nmol/L; p=0.001) and serum hepcidin (111.25 vs. 31.35 ng/mL; p<.0001) were significantly lower, while hemoglobin (12.10 vs.13.30 g/dL; p<.0001) and hematocrit(36.58 vs. 38.78% p=0.001) were significantly higher. Ferritin and transferrin saturation showed minimal improvement at follow-up. At baseline, hepcidin was not correlated with sTfR(r=0.02), however, at follow-up significant correlations were found(r=-0.58). Change in IL-6 from baseline was marginally associated with decreased log serum hepcidin(' IL-6: ß= -0.22; p= 0.15). No significant difference in dietary iron was noted post-surgery. Weight loss in obese pre-menopausal women is associated with reduced serum hepcidin and inflammation. Reduction in inflammation and hepcidin likely allows for enhanced dietary iron absorption resulting in an improved functional iron profile.