Relationship between Increased Body Iron Stores, Oxidative Stress and Insulin Resistance in Healthy Men

Syrovatka, Petr; Kraml, Pavel; Potočková, Jana; Fialová, L; Vejražka, Martin; Crkovská, J; Andĕl, M

doi:10.1159/000229507

Cited by 41 publications

(35 citation statements)

References 55 publications

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“…Similar observations were reported in obese teenagers, including increased transaminase levels; increased ferritin and transaminase levels are correlated [3,34,35,36,37,38,39,40]. Reduction of iron stores had positive influence on MetS and NAFLD; when occurring after a phlebotomy, these changes could be partly explained by its hemodynamic effects [41,42].…”

Section: Discussionsupporting

confidence: 68%

Iron in Child Obesity. Relationships with Inflammation and Metabolic Risk Factors

Bouglé

Brouard

2013

Nutrients

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Iron (Fe) sequestration is described in overweight and in its associated metabolic complications, i.e., metabolic syndrome (MetS) and non-alcoholic liver fatty disease (NAFLD); however, the interactions between Fe, obesity and inflammation make it difficult to recognize the specific role of each of them in the risk of obesity-induced metabolic diseases. Even the usual surrogate marker of Fe stores, ferritin, is influenced by inflammation; therefore, in obese subjects inflammation parameters must be measured together with those of Fe metabolism. This cross-sectional study in obese youth (502 patients; 57% girls): 11.4 ± 3.0 years old (x ± SD); BMI z score 5.5 ± 2.3), multivariate regression analysis showed associations between Fe storage assessed by serum ferritin with risk factors for MetS and NAFLD, assessed by transaminase levels, which were independent of overweight and the acute phase protein fibrinogen. Further studies incorporating the measurement of complementary parameters of Fe metabolism could improve the comprehension of mechanisms involved.

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Section: Discussionsupporting

confidence: 68%

Iron in Child Obesity. Relationships with Inflammation and Metabolic Risk Factors

Bouglé

Brouard

2013

Nutrients

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“…Moreover, insulin signaling in muscle is comparable to ϩ/b controls. These features were unexpected based on previous studies reporting impaired glucose metabolism in iron-loaded patients and animals (1,10,18,41). However, results from such studies have been inconsistent (2,15,23,38).…”

mentioning

confidence: 84%

Glucose metabolism in the Belgrade rat, a model of iron-loading anemia

Jia

Kim

Veuthey

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

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The iron-diabetes hypothesis proposes an association between iron overload and glucose metabolism that is supported by a number of epidemiological studies. The prevalence of type 2 diabetes in patients with hereditary hemochromatosis and iron-loading thalassemia supports this hypothesis. The Belgrade rat carries a mutation in the iron transporter divalent metal transporter 1 (DMT1) resulting in iron-loading anemia. In this study, we characterized the glycometabolic status of the Belgrade rat. Belgrade rats displayed normal glycemic control. Insulin signaling and secretion were not impaired, and pancreatic tissue did not incur damage despite high levels of nonheme iron. These findings suggest that loss of DMT1 protects against oxidative damage to the pancreas and helps to maintain insulin sensitivity despite iron overload. Belgrade rats had lower body weight but increased food consumption compared with heterozygous littermates. The unexpected energy balance was associated with increased urinary glucose output. Increased urinary excretion of electrolytes, including iron, was also observed. Histopathological evidence suggests that altered renal function is secondary to changes in kidney morphology, including glomerulosclerosis. Thus, loss of DMT1 appears to protect the pancreas from injury but damages the integrity of kidney structure and function.

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“…These observations link iron-catalyzed oxidation to inflammation and atherosclerosis (Sagastagoitia et al 2007). A likely role for ferritin binding to these proteins involved in clotting is to sequester iron to prevent iron catalyzed oxidative damage that inhibits these processes (Syrovatka et al 2009). Figure 3 shows all of these reactions, where ferritin binds and shows sites where ferritin may be important for sequestering iron to allow activity of the enzymes.…”

Section: Ferritin Binding Proteinsmentioning

confidence: 99%

The many faces of the octahedral ferritin protein

Watt

2011

Biometals

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Iron is an essential trace nutrient required for the active sites of many enzymes, electron transfer and oxygen transport proteins. In contrast, to its important biological roles, iron is a catalyst for reactive oxygen species (ROS). Organisms must acquire iron but must protect against oxidative damage. Biology has evolved siderophores, hormones, membrane transporters, and iron transport and storage proteins to acquire sufficient iron but maintain iron levels at safe concentrations that prevent iron from catalyzing the formation of ROS. Ferritin is an important hub for iron metabolism because it sequesters iron during times of iron excess and releases iron during iron paucity. Ferritin is expressed in response to oxidative stress and is secreted into the extracellular matrix and into the serum. The iron sequestering ability of ferritin is believed to be the source of the anti-oxidant properties of ferritin. In fact, ferritin has been used as a biomarker for disease because it is synthesized in response to oxidative damage and inflammation. The function of serum ferritin is poorly understood, however serum ferritin concentrations seem to correlate with total iron stores. Under certain conditions, ferritin is also associated with pro-oxidant activity. The source of this switch from anti-oxidant to pro-oxidant has not been established but may be associated with unregulated iron release from ferritin. Recent reports demonstrate that ferritin is involved in other aspects of biology such as cell activation, development, immunity and angiogenesis. This review examines ferritin expression and secretion in correlation with anti-oxidant activity and with respect to these new functions. In addition, conditions that lead to pro-oxidant conditions are considered.

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Relationship between Increased Body Iron Stores, Oxidative Stress and Insulin Resistance in Healthy Men

Cited by 41 publications

References 55 publications

Iron in Child Obesity. Relationships with Inflammation and Metabolic Risk Factors

Iron in Child Obesity. Relationships with Inflammation and Metabolic Risk Factors

Glucose metabolism in the Belgrade rat, a model of iron-loading anemia

The many faces of the octahedral ferritin protein

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