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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.

Background The excess burden of obesity among black women is well-documented. However, the behavioral weight loss intervention literature often does not report results by ethnic group or gender. Purpose The purpose of this article is to conduct a systematic review of all behavioral weight loss intervention trials published between 1990 and 2010 that included and reported results separately for black women. Methods The criteria for inclusion included: 1) participants age ≥18 years; 2) a behavioral weight loss intervention; 3) weight as an outcome variable; 4) inclusion of black women; and 5) weight loss results reported separately by ethnicity and gender. Results The literature search identified 25 studies that met inclusion criteria. Our findings suggest more intensive randomized behavioral weight loss trials with medically at-risk populations yield better results. Conclusions Well-designed and more intensive multi-site trials with medically at-risk populations currently offer the most promising results for black women. Still, black women lose less weight than other subgroups in behavioral weight loss interventions. It is now critical to expand on individual-level approaches and incorporate the biological, social, and environmental factors that influence obesity. This will help enable the adoption of healthier behaviors for this group of women disproportionately affected by obesity.

Hepcidin is the master regulator of systemic iron bioavailability in humans. This review examines primary research articles that assessed hepcidin during pregnancy and postpartum and report its relationship to maternal and infant iron status and birth outcomes; areas for future research are also discussed. A systematic search of the databases Medline and Cumulative Index to Nursing and Allied Health returned 16 primary research articles including 10 human and six animal studies. Collectively, the results indicate that hepcidin is lower during pregnancy than in a non-pregnant state, presumably to ensure greater iron bioavailability to the mother and fetus. Pregnant women with undetectable serum hepcidin transferred a greater quantity of maternally ingested iron to their fetus compared to women with detectable hepcidin, indicating that maternal hepcidin in part determines the iron bioavailability to the fetus. However, inflammatory states, including preeclampsia, malaria infection, and obesity were associated with higher hepcidin during pregnancy compared to healthy controls, suggesting that maternal and fetal iron bioavailability could be compromised in such conditions. Future studies should examine the relative contribution of maternal versus fetal hepcidin to the control of placental iron transfer as well as optimizing maternal and fetal iron bioavailability in pregnancies complicated by inflammation.

Objective Colorectal cancer (CRC) incidence is higher in African Americans (AAs) compared with non-Hispanic whites (NHWs). A diet high in animal protein and fat is an environmental risk factor for CRC development. The intestinal microbiota is postulated to modulate the effects of diet in promoting or preventing CRC. Hydrogen sulfide, produced by autochthonous sulfidogenic bacteria, triggers proinflammatory pathways and hyperproliferation, and is genotoxic. We hypothesised that sulfidogenic bacterial abundance in colonic mucosa may be an environmental CRC risk factor that distinguishes AA and NHW. Design Colonic biopsies from uninvolved or healthy mucosa from CRC cases and tumour-free controls were collected prospectively from five medical centres in Chicago for association studies. Sulfidogenic bacterial abundance in uninvolved colonic mucosa of AA and NHW CRC cases was compared with normal mucosa of AA and NHW controls. In addition, 16S rDNA sequencing was performed in AA cases and controls. Correlations were examined among bacterial targets, race, disease status and dietary intake. Results AAs harboured a greater abundance of sulfidogenic bacteria compared with NHWs regardless of disease status. Bilophila wadsworthia-specific dsrA was more abundant in AA cases than controls. Linear discriminant analysis of 16S rRNA gene sequences revealed five sulfidogenic genera that were more abundant in AA cases. Fat and protein intake and daily servings of meat were significantly higher in AAs compared with NHWs, and multiple dietary components correlated with a higher abundance of sulfidogenic bacteria. Conclusions These results implicate sulfidogenic bacteria as a potential environmental risk factor contributing to CRC development in AAs.

Adequate iron availability is essential to human development and overall health. Iron is a key component of oxygen-carrying proteins, has a pivotal role in cellular metabolism, and is essential to cell growth and differentiation. Inadequate dietary iron intake, chronic and acute inflammatory conditions, and obesity are each associated with alterations in iron homeostasis. Tight regulation of iron is necessary because iron is highly toxic and human beings can only excrete small amounts through sweat, skin and enterocyte sloughing, and fecal and menstrual blood loss. Hepcidin, a small peptide hormone produced mainly by the liver, acts as the key regulator of systemic iron homeostasis. Hepcidin controls movement of iron into plasma by regulating the activity of the sole known iron exporter ferroportin-1. Downregulation of the ferroportin-1 exporter results in sequestration of iron within intestinal enterocytes, hepatocytes, and iron-storing macrophages reducing iron bioavailability. Hepcidin expression is increased by higher body iron levels and inflammation and decreased by anemia and hypoxia. Importantly, existing data illustrate that hepcidin may play a significant role in the development of several iron-related disorders, including the anemia of chronic disease and the iron dysregulation observed in obesity. Therefore, the purpose of this article is to discuss iron regulation, with specific emphasis on systemic regulation by hepcidin, and examine the role of hepcidin within several disease states, including iron deficiency, anemia of chronic disease, and obesity. The relationship between obesity and iron depletion and the clinical assessment of iron status will also be reviewed.

Hepcidin is the principal iron-regulatory hormone and a pathogenic factor in anemia of inflammation. Patients with multiple myeloma (MM) frequently present with anemia. We showed that MM patients had increased serum hepcidin, which inversely correlated with hemoglobin, suggesting that hepcidin contributes to MMrelated anemia. Searching for hepcidininducing cytokines in MM, we quantified the stimulation of hepcidin promoterluciferase activity in HuH7 cells by MM sera. MM sera activated the hepcidin promoter significantly more than did normal sera. We then examined the role of bone morphogenetic proteins (BMPs) and interleukin-6 (IL-6), the major transcriptional regulators of hepcidin. Mutations in both BMP-responsive elements abrogated the activation dramatically, while mutations in the IL-6-responsive signal transducer and activator of transcription 3-binding site (STAT3-BS) had only a minor effect. Cotreatment with anti-BMP-2/4 or noggin-Fc blocked the promoter induction with all MM sera, anti-IL-6 blocked it with a minority of sera, whereas anti-BMP-4, -6, or -9 antibodies had no effect. BMP-2-immunodepleted MM sera had decreased promoter stimulatory capacity, and BMP-2 concentrations in MM sera were significantly higher than in normal sera. Our results demonstrate that BMP-2 is a major mediator of the hepcidin stimulatory activity of MM sera. (Blood. 2010;116(18):3635-3644) IntroductionMultiple myeloma (MM) is a malignant plasma cell disorder that accounts for approximately 10% of all hematologic cancers. 1 The disease is characterized by monoclonal proliferation of plasma cells together with overproduction of a monoclonal antibody, 2 often accompanied by anemia, hypercalcemia, renal insufficiency, or bone lesions. 3 Approximately 97% of MM patients develop anemia during the course of their illness, and 70% are anemic at diagnosis. The anemia is usually normocytic/normochromic, 4 serum-iron levels are normal to low, serum ferritin is high, and hemosiderin is prominent in bone marrow macrophages. 5 This suggests than iron release from reticuloendothelial macrophages is impaired, consistent with anemia of inflammation. 6 The main mediator of anemia of inflammation is the ironregulatory hormone, hepcidin. Hepcidin is produced by hepatocytes and acts on the iron exporter, ferroportin. Binding of hepcidin to ferroportin induces the internalization and degradation of ferroportin, thereby preventing cellular iron efflux and causing retention of iron, mainly inside enterocytes, macrophages, and hepatocytes. 7 Pathologic induction of hepcidin by inflammation causes hypoferremia, restricting the iron supply for erythropoiesis and, eventually, causing anemia. The interleukin-6 (IL-6)-hepcidin axis was shown to be important for inflammation-related hypoferremia. 8 However, in chronic inflammation, IL-6-independent pathways may also induce hepcidin mRNA. 9 Recently, 2 studies described the involvement of hepcidin in anemia of MM in humans. We reported that patients with stage III MM (n ϭ 44) at diagnosis had higher urinar...

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