scholarly journals Iron Metabolism in Obesity and Metabolic Syndrome

2020 ◽  
Vol 21 (15) ◽  
pp. 5529
Author(s):  
Álvaro González-Domínguez ◽  
Francisco M. Visiedo-García ◽  
Jesús Domínguez-Riscart ◽  
Raúl González-Domínguez ◽  
Rosa M. Mateos ◽  
...  
Keyword(s):  
Childhood Obesity ◽  
Iron Metabolism ◽  
Fenton Reaction ◽  
Iron Homeostasis ◽  
Living Organism ◽  
Nutritional Disorder ◽  
Nonalcoholic Fatty Liver ◽  
Pathological Conditions

Obesity is an excessive adipose tissue accumulation that may have detrimental effects on health. Particularly, childhood obesity has become one of the main public health problems in the 21st century, since its prevalence has widely increased in recent years. Childhood obesity is intimately related to the development of several comorbidities such as nonalcoholic fatty liver disease, dyslipidemia, type 2 diabetes mellitus, non-congenital cardiovascular disease, chronic inflammation and anemia, among others. Within this tangled interplay between these comorbidities and associated pathological conditions, obesity has been closely linked to important perturbations in iron metabolism. Iron is the second most abundant metal on Earth, but its bioavailability is hampered by its ability to form highly insoluble oxides, with iron deficiency being the most common nutritional disorder. Although every living organism requires iron, it may also cause toxic oxygen damage by generating oxygen free radicals through the Fenton reaction. Thus, iron homeostasis and metabolism must be tightly regulated in humans at every level (i.e., absorption, storage, transport, recycling). Dysregulation of any step involved in iron metabolism may lead to iron deficiencies and, eventually, to the anemic state related to obesity. In this review article, we summarize the existent evidence on the role of the most recently described components of iron metabolism and their alterations in obesity.

scholarly journals Role of folate in nonalcoholic fatty liver disease

2017 ◽  
Vol 95 (10) ◽  
pp. 1141-1148 ◽  
Author(s):  
Victoria Sid ◽  
Yaw L. Siow ◽  
Karmin O
Keyword(s):  
Type 2 Diabetes ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Serum Folate ◽  
Nonalcoholic Fatty Liver ◽  
Obesity And Diabetes

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of chronic liver conditions that are characterized by steatosis, inflammation, fibrosis, and liver injury. The global prevalence of NAFLD is rapidly increasing in proportion to the rising incidence of obesity and type 2 diabetes. Because NAFLD is a multifaceted disorder with many underlying metabolic abnormalities, currently, there is no pharmacological agent that is therapeutically approved for the treatment of this disease. Folate is a water-soluble B vitamin that plays an essential role in one-carbon transfer reactions involved in nucleic acid biosynthesis, methylation reactions, and sulfur-containing amino acid metabolism. The liver is the primary organ responsible for storage and metabolism of folates. Low serum folate levels have been observed in patients with obesity and diabetes. It has been reported that a low level of endogenous folates in rodents perturbs folate-dependent one-carbon metabolism, and may be associated with development of metabolic diseases such as NAFLD. This review highlights the biological role of folate in the progression of NAFLD and its associated metabolic complications including obesity and type 2 diabetes. Understanding the role of folate in metabolic disease may position this vitamin as a potential therapeutic for NAFLD.

scholarly journals Double-edge sword roles of iron in driving energy production versus instigating ferroptosis

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Shuping Zhang ◽  
Wei Xin ◽  
Gregory J. Anderson ◽  
Ruibin Li ◽  
Ling Gao ◽  
...  
Keyword(s):  
Fenton Reaction ◽  
Energy Production ◽  
Iron Homeostasis ◽  
Regulated Cell Death ◽  
Double Edge ◽  
Double Edge Sword ◽  
Novel Interactions ◽  
Metabolic Activities ◽  
Species Production

AbstractIron is vital for many physiological functions, including energy production, and dysregulated iron homeostasis underlies a number of pathologies. Ferroptosis is a recently recognized form of regulated cell death that is characterized by iron dependency and lipid peroxidation, and this process has been reported to be involved in multiple diseases. The mechanisms underlying ferroptosis are complex, and involve both well-described pathways (including the iron-induced Fenton reaction, impaired antioxidant capacity, and mitochondrial dysfunction) and novel interactions linked to cellular energy production. In this review, we examine the contribution of iron to diverse metabolic activities and their relationship to ferroptosis. There is an emphasis on the role of iron in driving energy production and its link to ferroptosis under both physiological and pathological conditions. In conclusion, excess reactive oxygen species production driven by disordered iron metabolism, which induces Fenton reaction and/or impairs mitochondrial function and energy metabolism, is a key inducer of ferroptosis.

scholarly journals Identification of new enterosynes using prebiotics: roles of bioactive lipids and mu-opioid receptor signalling in humans and mice

Gut ◽  
2020 ◽  
pp. gutjnl-2019-320230
Author(s):  
Anne Abot ◽  
Eve Wemelle ◽  
Claire Laurens ◽  
Adrien Paquot ◽  
Nicolas Pomie ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Enteric Neurons ◽  
Signalling Pathways ◽  
Bioactive Lipids ◽  
Mu Opioid Receptors ◽  
Mu Opioid ◽  
Receptor Signalling ◽  
Pathological Conditions

ObjectiveThe enteric nervous system (ENS) plays a key role in controlling the gut-brain axis under normal and pathological conditions, such as type 2 diabetes. The discovery of intestinal actors, such as enterosynes, able to modulate the ENS-induced duodenal contraction is considered an innovative approach. Among all the intestinal factors, the understanding of the role of gut microbes in controlling glycaemia is still developed. We studied whether the modulation of gut microbiota by prebiotics could permit the identification of novel enterosynes.DesignWe measured the effects of prebiotics on the production of bioactive lipids in the intestine and tested the identified lipid on ENS-induced contraction and glucose metabolism. Then, we studied the signalling pathways involved and compared the results obtained in mice to human.ResultsWe found that modulating the gut microbiota with prebiotics modifies the actions of enteric neurons, thereby controlling duodenal contraction and subsequently attenuating hyperglycaemia in diabetic mice. We discovered that the signalling pathway involved in these effects depends on the synthesis of a bioactive lipid 12-hydroxyeicosatetraenoic acid (12-HETE) and the presence of mu-opioid receptors (MOR) on enteric neurons. Using pharmacological approaches, we demonstrated the key role of the MOR receptors and proliferator-activated receptor γ for the effects of 12-HETE. These findings are supported by human data showing a decreased expression of the proenkephalin and MOR messanger RNAs in the duodenum of patients with diabetic.ConclusionsUsing a prebiotic approach, we identified enkephalin and 12-HETE as new enterosynes with potential real beneficial and safety impact in diabetic human.

scholarly journals Diabetes inHFEHemochromatosis

2017 ◽  
Vol 2017 ◽  
pp. 1-16 ◽  
Author(s):  
James C. Barton ◽  
Ronald T. Acton
Keyword(s):  
Type 2 Diabetes ◽  
Serum Ferritin ◽  
Iron Homeostasis ◽  
Reference Range ◽  
Clinical Manifestations ◽  
Diabetes Type 2 ◽  
Diabetes Risk ◽  
European Descent

Diabetes in whites of European descent with hemochromatosis was first attributed to pancreatic siderosis. Later observations revealed that the pathogenesis of diabetes inHFEhemochromatosis is multifactorial and its clinical manifestations are heterogeneous. Increased type 2 diabetes risk inHFEhemochromatosis is associated with one or more factors, including abnormal iron homeostasis and iron overload, decreased insulin secretion, cirrhosis, diabetes in first-degree relatives, increased body mass index, insulin resistance, and metabolic syndrome. In p.C282Y homozygotes, serum ferritin, usually elevated at hemochromatosis diagnosis, largely reflects body iron stores but not diabetes risk. In persons with diabetes type 2 without hemochromatosis diagnoses, serum ferritin levels are higher than those of persons without diabetes, but most values are within the reference range. Phlebotomy therapy to achieve iron depletion does not improve diabetes control in all persons withHFEhemochromatosis. The prevalence of type 2 diabetes diagnosed today in whites of European descent with and withoutHFEhemochromatosis is similar. Routine iron phenotyping orHFEgenotyping of patients with type 2 diabetes is not recommended. Herein, we review diabetes inHFEhemochromatosis and the role of iron in diabetes pathogenesis in whites of European descent with and withoutHFEhemochromatosis.

Hepcidin in Iron Homeostasis: Diagnostic and Therapeutic Implications in Type 2 Diabetes Mellitus Patients

2017 ◽  
Vol 138 (4) ◽  
pp. 183-193 ◽  
Author(s):  
Sintayehu Ambachew ◽  
Belete Biadgo
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Iron Overload ◽  
Iron Metabolism ◽  
Iron Homeostasis ◽  
Diabetic Patients ◽  
Hepatitis C Infection ◽  
Body Iron

The prevalence of type 2 diabetes is increasing in epidemic proportions worldwide. Evidence suggests body iron overload is frequently linked and observed in patients with type 2 diabetes. Body iron metabolism is based on iron conservation and recycling by which only a part of the daily need is replaced by duodenal absorption. The principal liver-produced peptide called hepcidin plays a fundamental role in iron metabolism. It directly binds to ferroportin, the sole iron exporter, resulting in the internalization and degradation of ferroportin. However, inappropriate production of hepcidin has been shown to play a role in the pathogenesis of type 2 diabetes mellitus and its complications, based on the regulation and expression in iron-abundant cells. Underexpression of hepcidin results in body iron overload, which triggers the production of reactive oxygen species simultaneously thought to play a major role in diabetes pathogenesis mediated both by β-cell failure and insulin resistance. Increased hepcidin expression results in increased intracellular sequestration of iron, and is associated with the complications of type 2 diabetes. Besides, hepcidin concentrations have been linked to inflammatory cytokines, matriptase 2, and chronic hepatitis C infection, which have in turn been reported to be associated with diabetes by several approaches. Either hepcidin-targeted therapy alone or as adjunctive therapy with phlebotomy, iron chelators, or dietary iron restriction may be able to alter iron parameters in diabetic patients. Therefore, measuring hepcidin may improve differential diagnosis and the monitoring of disorders of iron metabolism.

scholarly journals Disease Ionomics: Understanding the Role of Ions in Complex Disease

2020 ◽  
Vol 21 (22) ◽  
pp. 8646
Author(s):  
Yan Zhang ◽  
Yinzhen Xu ◽  
Lin Zheng
Keyword(s):  
Complex Disease ◽  
Dynamic Network ◽  
Complex Diseases ◽  
Living Organism ◽  
Future Trends ◽  
Pathological Conditions ◽  
Systematic Understanding ◽  
Elemental Profiling ◽  
Made In

Ionomics is a novel multidisciplinary field that uses advanced techniques to investigate the composition and distribution of all minerals and trace elements in a living organism and their variations under diverse physiological and pathological conditions. It involves both high-throughput elemental profiling technologies and bioinformatic methods, providing opportunities to study the molecular mechanism underlying the metabolism, homeostasis, and cross-talk of these elements. While much effort has been made in exploring the ionomic traits relating to plant physiology and nutrition, the use of ionomics in the research of serious diseases is still in progress. In recent years, a number of ionomic studies have been carried out for a variety of complex diseases, which offer theoretical and practical insights into the etiology, early diagnosis, prognosis, and therapy of them. This review aims to give an overview of recent applications of ionomics in the study of complex diseases and discuss the latest advances and future trends in this area. Overall, disease ionomics may provide substantial information for systematic understanding of the properties of the elements and the dynamic network of elements involved in the onset and development of diseases.

scholarly journals Role of iron metabolism-regulator hepcidin in perinatal iron homeostasis

2010 ◽  
Vol 151 (3) ◽  
pp. 83-91 ◽  
Author(s):  
Ádám Balogh ◽  
Szilvia Bősze ◽  
Kata Horváti ◽  
Gábor Mező ◽  
Sándor Kéki ◽  
...  
Keyword(s):  
Iron Metabolism ◽  
Iron Homeostasis

A hepcidin egy nemrégiben felfedezett, defenzin típusú peptid, amely központi szerepet játszik a vasháztartás szabályozásában. A hepcidin csökkenti a vastranszportban szerepet játszó molekulák expresszióját, így gátolja a vas gastrointestinalis rendszerből való felszívódását, makrofágokból való felszabadulását, csökkentve ezzel a szérum vasszintjét. A hepcidin vasháztartásban betöltött szerepének tisztázása segíthet a gyulladásos és krónikus betegségekben bekövetkező anémia pontosabb megértésében. Munkánk kezdetén a hepcidin kimutatására alkalmas, kereskedelmi forgalomban elérhető módszer nem állt rendelkezésre. Célunk volt egy, a vizelethepcidin kimutatására alkalmas módszer kidolgozása, valamint hogy ezen módszer segítségével vizsgáljuk a hepcidin jelentőségét a perinatalis vasháztartásban. Munkánk során a natív, emberi hepcidin aminosav-szekvenciájának megfelelően állítottunk elő peptidszármazékokat, amelyek közül az 1-7 peptidszármazékról igazoltuk, hogy alkalmas lehet a natív hepcidin standard helyettesítésére immunreakción alapuló módszerek fejlesztésekor. Kidolgoztunk egy, az emberi vizelethepcidin mennyiségi meghatározására alkalmas, lézerdeszorpciós tömegspektrometriás, szemikvantitatív módszert, amelyben az általunk szintetizált acetil-1-25 peptidszármazékot mint hepcidinszerű belső standardot elsőként alkalmaztuk. Kidolgoztunk a vizelet tisztítására és a vizelethepcidin koncentrálására alkalmas, szilárd fázisú extrakción alapuló módszert. Az általunk kidolgozott módszerrel elsőként mértük egészséges újszülöttek vizelethepcidin-szintjét, valamint egy kereskedelmi forgalomban elérhető módszerrel a szérumprohepcidin-szintjét. Kimutattuk, hogy az érett újszülöttek korai adaptációja során a szérumprohepcidin-szint nem változik, a vizelethepcidin viszont szignifikánsan nő. A szérumprohepcidin- és a vizelethepcidin-szintek egymással nem mutattak összefüggést. Kimutattuk, hogy az érett újszülöttek vasháztartásának korai adaptációja során a szérumprohepcidin-szintek kizárólag a vörösvérsejtek átlagos hemoglobinkoncentrációjával, míg a vizelethepcidin-szintek a szérumvasszinttel és teljes vaskötő kapacitással mutattak összefüggést. Kimutattuk, hogy az érett újszülöttek vasháztartásának korai adaptációja során a köldökzsinórvér-mintákban az alacsonyabb szérumprohepcidin-szintek esetén szabad vas jelenléte igazolható. Összefoglalva: Eredményeink alapján elmondhatjuk, hogy a hepcidinnek valószínűleg szerepe van az újszülöttek korai, a vasháztartást érintő adaptációjában, azonban további vizsgálatok szükségesek ahhoz, hogy ezt az összefüggést biztosan megállapíthassuk.

scholarly journals Angiopoietin 1 release from human neutrophils is independent from neutrophil extracellular traps (NETs)

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Elcha Charles ◽  
Benjamin L. Dumont ◽  
Steven Bonneau ◽  
Paul-Eduard Neagoe ◽  
Louis Villeneuve ◽  
...  
Keyword(s):  
Nuclear Dna ◽  
Neutrophil Extracellular Traps ◽  
Innate Immune ◽  
Human Neutrophils ◽  
Extracellular Traps ◽  
Pathological Conditions ◽  
Healthy Control ◽  
Angiopoietin 1

Abstract Background Neutrophils induce the synthesis and release of angiopoietin 1 (Ang1), a cytosolic growth factor involved in angiogenesis and capable of inducing several pro-inflammatory activities in neutrophils. Neutrophils also synthesize and release neutrophil extracellular traps (NETs), comprised from decondensed nuclear DNA filaments carrying proteins such as neutrophil elastase (NE), myeloperoxidase (MPO), proteinase 3 (PR3) and calprotectin (S100A8/S100A9), which together, contribute to the innate immune response against pathogens (e.g., bacteria). NETs are involved in various pathological conditions through pro-inflammatory, pro-thrombotic and endothelial dysfunction effects and have recently been found in heart failure (HF) and type 2 diabetes (T2DM) patients. The aim of the present study was to investigate the role of NETs on the synthesis and release of Ang1 by the neutrophils in patients with T2DM and HF with preserved ejection fraction (HFpEF) (stable or acute decompensated; ADHFpEF) with or without T2DM. Results Our data show that at basal level (PBS) and upon treatment with LPS, levels of NETs are slightly increased in patients suffering from T2DM, HFpEF ± T2DM and ADHF without (w/o) T2DM, whereas this increase was significant in ADHFpEF + T2DM patients compared to healthy control (HC) volunteers and ADHFpEF w/o T2DM. We also observed that treatments with PMA or A23187 increase the synthesis of Ang1 (from 150 to 250%) in HC and this effect is amplified in T2DM and in all cohorts of HF patients. Ang1 is completely released (100%) by neutrophils of all groups and does not bind to NETs as opposed to calprotectin. Conclusions Our study suggests that severely ill patients with HFpEF and diabetes synthesize and release a greater abundance of NETs while Ang1 exocytosis is independent of NETs synthesis.

scholarly journals Normal systemic iron homeostasis in mice with macrophage-specific deletion of transferrin receptor 2

2016 ◽  
Vol 310 (3) ◽  
pp. G171-G180 ◽  
Author(s):  
Gautam Rishi ◽  
Eriza S. Secondes ◽  
Daniel F. Wallace ◽  
V. Nathan Subramaniam
Keyword(s):  
Iron Metabolism ◽  
Knockout Mice ◽  
Transferrin Receptor ◽  
Iron Homeostasis ◽  
Essential Element ◽  
Cellular Growth ◽  
Hepatic Expression ◽  
Specific Deletion ◽  
Transferrin Receptor 2

Iron is an essential element, since it is a component of many macromolecules involved in diverse physiological and cellular functions, including oxygen transport, cellular growth, and metabolism. Systemic iron homeostasis is predominantly regulated by the liver through the iron regulatory hormone hepcidin. Hepcidin expression is itself regulated by a number of proteins, including transferrin receptor 2 (TFR2). TFR2 has been shown to be expressed in the liver, bone marrow, macrophages, and peripheral blood mononuclear cells. Studies from our laboratory have shown that mice with a hepatocyte-specific deletion of Tfr2 recapitulate the hemochromatosis phenotype of the global Tfr2 knockout mice, suggesting that the hepatic expression of TFR2 is important in systemic iron homeostasis. It is unclear how TFR2 in macrophages contributes to the regulation of iron metabolism. We examined the role of TFR2 in macrophages by analysis of transgenic mice lacking Tfr2 in macrophages by crossing Tfr2 f/f mice with LysM-Cre mice. Mice were fed an iron-rich diet or injected with lipopolysaccharide to examine the role of macrophage Tfr2 in iron- or inflammation-mediated regulation of hepcidin. Body iron homeostasis was unaffected in the knockout mice, suggesting that macrophage TFR2 is not required for the regulation of systemic iron metabolism. However, peritoneal macrophages of knockout mice had significantly lower levels of ferroportin mRNA and protein, suggesting that TFR2 may be involved in regulating ferroportin levels in macrophages. These studies further elucidate the role of TFR2 in the regulation of iron homeostasis and its role in regulation of ferroportin and thus macrophage iron homeostasis.

scholarly journals Role of Dietary Flavonoids in Iron Homeostasis

2019 ◽  
Vol 12 (3) ◽  
pp. 119 ◽  
Author(s):  
Marija Lesjak ◽  
Surjit K. S. Srai
Keyword(s):  
Iron Metabolism ◽  
Iron Homeostasis ◽  
Iron Absorption ◽  
Therapeutic Potential ◽  
State Of The Art ◽  
Iron Status ◽  
Dietary Factors ◽  
The Body ◽  
Dietary Flavonoids

Balancing systemic iron levels within narrow limits is critical for human health, as both iron deficiency and overload lead to serious disorders. There are no known physiologically controlled pathways to eliminate iron from the body and therefore iron homeostasis is maintained by modifying dietary iron absorption. Several dietary factors, such as flavonoids, are known to greatly affect iron absorption. Recent evidence suggests that flavonoids can affect iron status by regulating expression and activity of proteins involved the systemic regulation of iron metabolism and iron absorption. We provide an overview of the links between different dietary flavonoids and iron homeostasis together with the mechanism of flavonoids effect on iron metabolism. In addition, we also discuss the clinical relevance of state-of-the-art knowledge regarding therapeutic potential that flavonoids may have for conditions that are low in iron such as anaemia or iron overload diseases.

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