Context-Obesity is associated with hypoferremia, but it is unclear if this condition is caused by insufficient iron stores or diminished iron availability related to inflammation-induced iron sequestration.Objective-To examine the relationships between obesity, serum iron, measures of iron intake, iron stores and inflammation. We hypothesized that both inflammation-induced sequestration of iron and true iron deficiency were involved in the hypoferremia of obesity.Design-Cross-sectional analysis of factors anticipated to affect serum iron. Setting-Outpatient clinic visits.Patients-Convenience sample of 234 obese and 172 non-obese adults.Main outcome measures-Relationships between serum iron, adiposity, and serum transferrin receptor, C-reactive protein, ferritin, and iron intake analyzed by analysis of covariance and multiple linear regression.Results-Serum iron was lower (75.8 ± 35.2 vs 86.5 ± 34.2 g/dl, P=0.002), whereas transferrin receptor (22.6 ± 7.1 vs 21.0 ± 7.2 nmol/l, P=0.026), C-reactive protein (0.75 ± 0.67 vs 0.34±0.67 mg/dl, P<0.0001) and ferritin (81.1 ± 88.8 vs 57.6 ± 88.7 mg/l, P=0.009) were higher in obese than non-obese subjects. Obese subjects had a higher prevalence of iron deficiency defined by serum iron (24.3%, confidence intervals (CI) 19.3-30.2 vs 15.7%, CI 11.0-21.9%, P=0.03) and transferrin receptor (26.9%, CI 21.6-33.0 vs 15.7%, CI 11.0-21.9%, P=0.0078) but not by ferritin (9.8%, CI 6.6-14.4 vs 9.3%, CI 5.7-14.7%, P=0.99). Transferrin receptor, ferritin and C-reactive protein contributed independently as predictors of serum iron.Conclusions-The hypoferremia of obesity appears to be explained both by true iron deficiency and by inflammatory-mediated functional iron deficiency.

BACKGROUND-Brain-derived neurotrophic factor (BDNF) has been found to be important in energy homeostasis in animal models, but little is known about its role in energy balance in humans. Heterozygous, variably sized, contiguous gene deletions causing haploinsufficiency of the WT1 and PAX6 genes on chromosome 11p13, approximately 4 Mb centromeric to BDNF (11p14.1), result in the Wilms' tumor, aniridia, genitourinary anomalies, and mental retardation (WAGR) syndrome. Hyperphagia and obesity were observed in a subgroup of patients with the WAGR syndrome. We hypothesized that the subphenotype of obesity in the WAGR syndrome is attributable to deletions that induce haploinsufficiency of BDNF.

Hypoferremia is more prevalent in obese than nonobese adults, but the reason for this phenomenon is unknown. To elucidate the role dietary factors play in obesity-related hypoferremia, the intake of heme and nonheme iron and the intake of other dietary factors known to affect iron absorption were compared cross-sectionally from April 2002 to December 2003 in a convenience sample of 207 obese and 177 nonobese adults. Subjects completed 7-day food records, underwent phlebotomy for serum iron measurement, and had body composition assessed by dual-energy x-ray absorptiometry, during a 21-month period. Data were analyzed by analysis of covariance and multiple linear regression. Serum iron (mean±standard deviation) was significantly lower in obese than nonobese individuals (72.0±61.7 vs 85.3±58.1 µg/dL [12.888±11.0443 vs 15.2687±10.3999 µmol/L]; P<0.001). The obese cohort reported consuming more animal protein (63.6±34.5 vs 55.7±32.5 g/day; P<0.001) and more heme iron (3.6±2.8 vs 2.7±2.6 mg/day; P<0.001). Groups did not differ, however, in total daily iron consumption, including supplements. Obese subjects reported consuming less vitamin C (77.2±94.9 vs 91.8±89.5 mg/day; P=0.01), which may increase absorption of nonheme iron, and less calcium (766.2±665.0 vs 849.0±627.2 mg/day; P=0.038), which may decrease nonheme iron absorption, than nonobese subjects. Groups did not significantly differ in intake of other dietary factors that can impact absorption of iron, including phytic acid, oxalic acid, eggs, coffee, tea, zinc, vegetable protein, or copper. After accounting for demographic covariates and dietary factors expected to affect iron absorption, fat mass (P=0.007) remained a statistically significant negative predictor of serum iron. This cross-sectional, exploratory study suggests that obesity-related hypoferremia is not associated with differences in reported intake of heme and nonheme iron or intake of dietary factors that can affect iron absorption.Several studies in children and adults have shown that obesity is associated with low serum iron concentrations (1-3) and a greater prevalence of iron deficiency (4). However, the pathophysiological mechanisms leading to hypoferremia among obese individuals are unknown. One proposed mechanism is an iron-poor diet (5). However, a difference in iron intake between obese and nonobese subjects has not been shown among US adults.

WAGR (Wilms tumor, Aniridia, Genitourinary malformations and mental Retardation) syndrome is a rare genomic disorder caused by deletion of the 11p14-p12 chromosome region. The majority of WAGR patients have mental retardation and behavioral problems, and more than 20% of the patients also have features of autism. While the Wilms tumor/genitourinary anomalies and aniridia are caused by deletion of WT1 and PAX6 respectively, the genomic cause of mental retardation and autism in WAGR syndrome remains unknown. Using oligonucleotide arrays, we have characterized the 11p14-p12 deletions in 31 patients and identified all the genes involved in each deletion. The deletions had sizes ranging from 4.9 to 23 Mb that encompass 18–62 genes (40 on average). In addition to WT1 and PAX6, all the patients had deletion of PRRG4 (transmembrane gamma-carboxyglutamic acid protein 4). The majority of them had deletion of BDNF (brain-derived neurotrophic factor) and SLC1A2 [solute carrier family 1 (glial high affinity glutamate transporter) member 2]. Deletion of BDNF and SLC1A2 occurred in patients with autism more frequently than in those without autism. Literature review on the functions of the genes suggests that haploinsufficiency of SLC1A2, PRRG4, and BDNF may contribute to mental retardation and behavioral problems. In particular, BDNF may modulate the risk of autism in WAGR patients as suggested by its link with Rett syndrome as a target of MECP2. We observed that all the de novo deletions occurred in the chromosome 11 inherited from the father in the families genotyped, implying a predisposition for de novo mutations occurring in spermatogenesis and possible involvement of imprinting in cognitive impairment in WAGR patients.

All three FFQs performed reasonably well at estimating dietary calcium intake compared to food records; each may be appropriate for use in select clinical and research settings.