Mutual interaction between iron homeostasis and obesity pathogenesis

Nikonorov, Alexandr А.; Skalnaya, Margarita G.; Tinkov, Alexey A.; Skalny, Anatoly V.

doi:10.1016/j.jtemb.2014.05.005

Cited by 60 publications

(47 citation statements)

References 142 publications

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“…These data are contradictory to the results of the earlier studies demonstrating that obesity is accompanied by iron deficiency in general and hypoferremia in particular [59]. However, we also failed to detect an increase in adipose tissue iron resulting from its sequestration [12]. At the same time, earlier data obtained by Suliburska demonstrated that 6-week diet high in fat, fructose, and salt did not significantly alter liver metal content [60].…”

Section: Discussioncontrasting

confidence: 99%

“…In particular, trace elements like Cr, Zn, V, and Se are considered to be the key elements in glucometabolic disorders due to their insulinmimetic and antioxidant effect [10]. Moreover, numerous studies also demonstrated alteration of iron homeostasis in obesity [11,12] Multiple clinical [13][14][15][16][17] and experimental [18][19][20][21][22] studies demonstrated a tight interplay between trace element balance and obesity-related disorders. At the same time, the majority of experimental data are based on dietary intervention in adult animals, whereas data on the influence of dietary regimen on trace element status in early age are insufficient.…”

Section: Introductionmentioning

confidence: 99%

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Early High-Fat Feeding Induces Alteration of Trace Element Content in Tissues of Juvenile Male Wistar Rats

Tinkov

Gatiatulina

Popova

et al. 2016

Biol Trace Elem Res

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The primary objective of the current study was to assess the influence of early high-fat feeding on tissue trace element content in young male Wistar rats. Twenty weanling male Wistar rats were divided into two groups fed standard (STD) or high-fat diet (HFD) containing 10 and 31.6 % of total calories from fat, respectively, for 1 month. Serum lipid spectrum, apolipoproteins, glucose, insulin, adiponectin, and leptin levels were assessed. The level of trace elements was estimated using inductively coupled plasma mass spectrometry. High-fat feeding significantly increased epidydimal (EDAT) and retroperitoneal adipose tissue (RPAT), as well as total adipose tissue mass by 34, 103, and 59 %, respectively. Serum leptin levels in HFD animals were twofold higher than those in the control rats. No significant difference in serum lipid spectrum, apolipoproteins, glucose, adiponectin, and insulin was detected between the groups. HFD significantly altered tissue trace element content. In particular, HFD-fed animals were characterized by significantly lower levels of Cu, I, Mn, Se, and Zn in the liver; Cr, V, Co, Cu, Fe, and I content of EDAT; Co, Cu, I, Cr, V, Fe, and Zn concentration in RPAT samples. At the same time, only serum Cu was significantly depressed in HFD-fed animals as compared to the control ones. Hair Co, Mn, Si, and V levels were significantly increased in comparison to the control values, whereas Se and I content was decreased. HFD feeding induced excessive adiposity and altered tissue trace element content in rats without insulin resistance, adiponectin deficiency, and proatherogenic state. Hypothetically, trace element disbalance may precede obesity-associated metabolic disturbances.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Early High-Fat Feeding Induces Alteration of Trace Element Content in Tissues of Juvenile Male Wistar Rats

Tinkov

Gatiatulina

Popova

et al. 2016

Biol Trace Elem Res

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“…The interest in this association is still evident, as several studies were undertaken in developed countries between the years 2000 and 2011, which show that obesity is associated with iron deficiency [3][4][5][6]. Furthermore, there are a number of recent review publications on this subject [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Conflicting effects of BMI and waist circumference on iron status

Choma

Alberts

Modjadji

2015

Journal of Trace Elements in Medicine and Biology

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“…Precisely why elevations in ferritin levels or systemic iron overload are associated with these conditions is not entirely clear, with potential explanations ranging from excess iron causing oxidative stress, endoplasmic reticulum (ER) stress, inflammation, and dysfunction of adipose tissue (Hubler et al 2015;Nikonorov et al 2015).…”

mentioning

confidence: 99%

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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Mutual interaction between iron homeostasis and obesity pathogenesis

Cited by 60 publications

References 142 publications

Early High-Fat Feeding Induces Alteration of Trace Element Content in Tissues of Juvenile Male Wistar Rats

Early High-Fat Feeding Induces Alteration of Trace Element Content in Tissues of Juvenile Male Wistar Rats

Conflicting effects of BMI and waist circumference on iron status

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

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