Increased Adipose Tissue Expression of Hepcidin in Severe Obesity Is Independent From Diabetes and NASH

Bekri, Soumeya; Gual, Philippe; Anty, Rodolphe; Luciani, Nathalie; Dahman, M.; Ramesh, Bala; Iannelli, Antonio; Staccini-Myx, A.; Casanova, Dominique; Amor, Imed Ben; Saint–Paul, Marie–Christine; Huet, Pierre‐Michel; Sadoul, Jean‐Louis; Gugenheim, Jean; Srai, Surjit Kaila; Tran, Albert; Marchand-Brustel, Y. Le

doi:10.1053/j.gastro.2006.07.007

Cited by 431 publications

(418 citation statements)

References 42 publications

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“…Although it is increasingly clear that adipocytes use much of the iron metabolism apparatus that is used in other tissues, such as transferrin receptor 1, hepcidin, and ferroportin, we are not aware of any human data that have addressed the degree to which adipose tissue iron is mobilized by venesection 9, 39. Another limitation of our study is the lack of liver histology.…”

Section: Discussionmentioning

confidence: 95%

Hepatic iron concentration correlates with insulin sensitivity in nonalcoholic fatty liver disease

Britton

Bridle

Reiling

et al. 2018

Hepatology Communications

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Rodent and cell‐culture models support a role for iron‐related adipokine dysregulation and insulin resistance in the pathogenesis of nonalcoholic fatty liver disease (NAFLD); however, substantial human data are lacking. We examined the relationship between measures of iron status, adipokines, and insulin resistance in patients with NAFLD in the presence and absence of venesection. This study forms part of the Impact of Iron on Insulin Resistance and Liver Histology in Nonalcoholic Steatohepatitis (IIRON2) study, a prospective randomized controlled trial of venesection for adults with NAFLD. Paired serum samples at baseline and 6 months (end of treatment) in controls (n = 28) and patients who had venesection (n = 23) were assayed for adiponectin, leptin, resistin, retinol binding protein‐4, tumor necrosis factor α, and interleukin‐6, using a Quantibody, customized, multiplexed enzyme‐linked immunosorbent assay array. Hepatic iron concentration (HIC) was determined using MR FerriScan. Unexpectedly, analysis revealed a significant positive correlation between baseline serum adiponectin concentration and HIC, which strengthened after correction for age, sex, and body mass index (rho = 0.36; P = 0.007). In addition, there were significant inverse correlations between HIC and measures of insulin resistance (adipose tissue insulin resistance (Adipo‐IR), serum insulin, serum glucose, homeostasis model assessment of insulin resistance, hemoglobin A1c, and hepatic steatosis), whereas a positive correlation was noted with the insulin sensitivity index. Changes in serum adipokines over 6 months did not differ between the control and venesection groups. Conclusion: HIC positively correlates with serum adiponectin and insulin sensitivity in patients with NAFLD. Further study is required to establish causality and mechanistic explanations for these associations and their relevance in the pathogenesis of insulin resistance and NAFLD. (Hepatology Communications 2018;2:644‐653)

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Section: Discussionmentioning

confidence: 95%

Hepatic iron concentration correlates with insulin sensitivity in nonalcoholic fatty liver disease

Britton

Bridle

Reiling

et al. 2018

Hepatology Communications

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“…Hepcidin is a small peptide hormone secreted by the liver and by adipocytes. 30 Hepcidin is an acute-phase reactant, 31 and its expression is increased in chronic inflammatory states 32,33 including obesity. 30 Hepcidin can inhibit enterocyte iron absorption 34 and has further been shown to inhibit the release of non-heme iron from macrophages.…”

Section: Discussionmentioning

confidence: 99%

Inflammation and iron deficiency in the hypoferremia of obesity

et al. 2007

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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.

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“…45 Our findings in the Thai women demonstrate for the first time that greater adiposity is associated with lower fractional iron absorption in humans, independent of iron status (Figure 2). Hepcidin expression is increased in obesity 25 and other chronic inflammatory states. 46 Increased circulating hepcidin may reduce both gastrointestinal iron absorption 26 and iron release from the reticuloendothelial system.…”

Section: Discussionmentioning

confidence: 99%

“…[19][20][21][22][23] Although the mechanism is unclear, this may be due to lower iron intakes and/or increased iron requirements in overweight individuals. 14,23 In addition, the chronic inflammation and increased leptin production characteristic of obesity increase hepcidin secretion from the liver, 24 which, along with hepcidin produced by adipose tissue, 25 could reduce dietary iron absorption. 26 The major adverse effects of iron deficiency are impaired cognitive development in children 27 and poorer pregnancy outcome in women.…”

Section: Introductionmentioning

confidence: 99%

Adiposity in women and children from transition countries predicts decreased iron absorption, iron deficiency and a reduced response to iron fortification

et al. 2008

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Background: Overweight is increasing in transition countries, while iron deficiency remains common. In industrialized countries, greater adiposity increases risk of iron deficiency. Higher hepcidin levels in obesity may reduce dietary iron absorption. Therefore, we investigated the association between body mass index (BMI) and iron absorption, iron status and the response to iron fortification in populations from three transition countries (Thailand, Morocco and India). Methods: In Thai women (n ¼ 92), we examined the relationship between BMI and iron absorption from a reference meal containing B4 mg of isotopically labeled fortification iron. We analyzed data from baseline (n ¼ 1688) and intervention (n ¼ 727) studies in children in Morocco and India to look for associations between BMI Z-scores and baseline hemoglobin, serum ferritin and transferrin receptor, whole blood zinc protoporphyrin and body iron stores, and changes in these measures after provision of iron. Results: In the Thai women, 20% were iron deficient and 22% were overweight. Independent of iron status, a higher BMI Z-score was associated with decreased iron absorption (P ¼ 0.030). In the Indian and Moroccan children, 42% were iron deficient and 6.3% were overweight. A higher BMI Z-score predicted poorer iron status at baseline (Po0.001) and less improvement in iron status during the interventions (Po0.001). Conclusions: Adiposity in young women predicts lower iron absorption, and pediatric adiposity predicts iron deficiency and a reduced response to iron fortification. These data suggest the current surge in overweight in transition countries may impair efforts to control iron deficiency in these target groups. Interactions of the 'double burden' of malnutrition during the nutrition transition may have adverse consequences.

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Increased Adipose Tissue Expression of Hepcidin in Severe Obesity Is Independent From Diabetes and NASH

Cited by 431 publications

References 42 publications

Hepatic iron concentration correlates with insulin sensitivity in nonalcoholic fatty liver disease

Hepatic iron concentration correlates with insulin sensitivity in nonalcoholic fatty liver disease

Inflammation and iron deficiency in the hypoferremia of obesity

Adiposity in women and children from transition countries predicts decreased iron absorption, iron deficiency and a reduced response to iron fortification

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