Effects of excess dietary iron and fat on glucose and lipid metabolism

Choi, Joo Sun; Koh, In-Uk; Lee, Hyo‐Jung; Kim, Won‐Ho; Song, Jihyun

doi:10.1016/j.jnutbio.2013.02.004

Cited by 71 publications

(67 citation statements)

References 39 publications

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“…It is a common component of many biological systems such as bio-imaging, blood circulation (128,129), energy production (130), enzyme catalysis (131,132) and immune system (133). Iron oxide nanoparticles (IONP) have drawn considerable attention in medical field.…”

Section: Iron Nanoparticlesmentioning

confidence: 99%

Nanotoxicity of Inert Materials: The Case of Gold, Silver and Iron

et al. 2016

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-Nanotechnology has opened a new horizon of research in various fields including applied physics, chemistry, electronics, optics, robotics, biotechnology and medicine. In the biomedical field, nanomaterials have shown remarkable potential as theranostic agents. Materials which are considered inert are often used in nanomedicine owning to their nontoxic profile. At nanoscale, these inert materials have shown unique properties that differ from bulk and dissolved counterparts. In the case of metals, this unique behavior not only imparts paramount advantages but also confers toxicity due to their unwanted interaction with different cellular processes. In the literature, the toxicity of nanoparticles made from inert materials has been investigated and many of these have revealed toxic potential under specific conditions. The surge to understand underlying mechanism of toxicity has increased and different means have been employed to overcome toxicity problems associated with these agents. In this review, we have focused nanoparticles of three inert metallic materials i.e. gold, silver and iron as these are regarded as biologically inert in the bulk and dissolved form. These materials have gained wider research interest and studies indicating the toxicity of these materials are also emerging. Oxidative stress, physical binding and interference with intracellular signaling are the major role player in nanotoxicity and their predominance is highly dependent upon size, surface coating and administered dose of nanoparticles. Current strategies to overcome toxicity have also been reviewed in the light of recent literature. The authors also suggested that uniform testing standards and well-designed studies are needed to evaluate nanotoxicity of these materials that are otherwise considered as inert.

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Section: Iron Nanoparticlesmentioning

confidence: 99%

Nanotoxicity of Inert Materials: The Case of Gold, Silver and Iron

et al. 2016

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“…The combination of iron and lipid-rich diet may exacerbate this situation because lipids also cause oxidative and ER stress, as well as inflammation. Collectively, this helps explain why dietary iron supplementation concurrent with a high-fat diet (HFD) greatly increases adiposity in rats (Tinkov et al 2013), as well as hepatic fat accumulation in the liver of mice (Choi et al 2013). The association seems to also hold true in reverse.…”

mentioning

confidence: 93%

Iron Overload Coordinately Promotes Ferritin Expression and Fat Accumulation in Caenorhabditis elegans

Wang¹,

Jiang

et al. 2016

Genetics

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The trace element iron is crucial for living organisms, since it plays essential roles in numerous cellular functions. Systemic iron overload and the elevated level of ferritin, a ubiquitous intracellular protein that stores and releases iron to maintain the iron homeostasis in cells, has long been epidemiologically associated with obesity and obesity-related diseases. However, the underlying mechanisms of this association remain unclear. Here, using Caenorhabditis elegans, we show that iron overload induces the expression of sgk-1, encoding the serum and glucocorticoid-inducible kinase, to promote the level of ferritin and fat accumulation. Mutation of cyp-23A1, encoding a homolog of human cytochrome P450 CYP7B1 that is related to neonatal hemochromatosis, further enhances the elevated expression of ftn-1, sgk-1, and fat accumulation. sgk-1 positively regulates the expression of acs-20 and vit-2, genes encoding homologs of the mammalian FATP1/4 fatty acid transport proteins and yolk lipoproteins, respectively, to facilitate lipid uptake and translocation for storage under iron overload. This study reveals a completely novel pathway in which sgk-1 plays a central role to synergistically regulate iron and lipid homeostasis, offering not only experimental evidence supporting a previously unverified link between iron and obesity, but also novel insights into the pathogenesis of iron and obesity-related human metabolic diseases. KEYWORDS iron; serum and glucocorticoid inducible kinase SGK-1; lipid uptake; obesity; C. elegans D UE to its essential roles in numerous cellular functions across nearly all living organisms, including oxygen transport, electron transport, DNA synthesis, and enzyme catalysis, exploring how iron is stored and regulated has been a growing focus in numerous fields. Dietary iron is absorbed primarily by duodenal enterocytes via the divalent metal-ion transporter 1 (DMT1) after it is reduced at the apical membrane. Subsequently, it is either stored in ferritin, which dynamically regulates iron sequestration, storage, and release or it is transported from enterocytes into the blood stream via the basolateral transporter ferroportin (Fleming and Ponka 2012). Consequently, the total amount of iron in the body is determined by its intake and storage, which are all finely regulated by many factors and signaling pathways at various levels (Fleming and Ponka 2012;Hubler et al. 2015), many of which not entirely understood.Human epidemiology studies revealed that elevated levels of ferritin may be an indication of systemic iron overload (Cook et al. 1974;Zimmermann 2008) and are positively associated with obesity (Wenzel et al. 1962;Gillum 2001;Iwasaki et al. 2005) and obesity-related diseases such as diabetes, hypertension, dyslipidaemia, or nonalcoholic fatty liver disease (Jehn et al. 2004;Bozzini et al. 2005;Mascitelli et al. 2009;Dongiovanni et al. 2011;Kim et al. 2011; see Zafon et al. 2010 for review). Precisely why elevations in ferritin levels or systemic iron overload are associated w...

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“…By using dietary experimental models, some studies have also suggested a reverse connection between iron and steatosis in rat livers [23,24] . In contrast, another study with a mouse dietary model of iron and high fat failed to show any significant effect of iron on steatosis [25] . The consequences of altered iron homeostasis for lipid metabolism in the liver are therefore unclear.…”

Section: Introductionmentioning

confidence: 81%

“…The mechanisms by which excess iron contribute to NAFLD pathogenesis is unclear. Although inconclusive, some studies suggested a role for iron in the regulation of lipid metabolism [23][24][25] . Since hepcidin is the central regulator of iron metabolism, we investigated its role in fatty liver disease.…”

Section: Discussionmentioning

confidence: 99%