Iron reduction by deferoxamine leads to amelioration of adiposity via the regulation of oxidative stress and inflammation in obese and type 2 diabetes KKAy mice

Tajima, Soichiro; Ikeda, Yasumasa; Sawada, Kaori; Yamano, Noriko; Horinouchi, Yuya; Kihira, Yoshitaka; Ishizawa, Keisuke; Izawa‐Ishizawa, Yuki; Kawazoe, Kazuyoshi; Tomita, Shuhei; Minakuchi, Kazuo; Tsuchiya, Koichiro; Takahashi, Toshiaki

doi:10.1152/ajpendo.00033.2011

Cited by 91 publications

(103 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In fact, both Tf gene expression and the release of transferrin protein increased during adipocyte differentiation in parallel with adipogenic genes (in both 3T3-L1 cells and human adipocytes). Administration of transferrin, as an iron donor, is well known to facilitate adipocyte differentiation [28,29], but we found no studies of the possible role of endogenous adipocyte transferrin. In fact, human adipose tissue transferrin gene and protein expression was found to be associated positively with adipogenic, and negatively with inflammatory, gene expression [15].…”

Section: Intracellular Iron Deficiency Impairs Adipogenesismentioning

confidence: 56%

“…Supporting this hypothesis, findings in human adipose tissue revealed that ISCA2 (an important mediator in Fe-S cluster biogenesis) and TF gene expression were positively associated with expression of PPARGC1A, whereas the expression of CYBA, which is a marker for intracellular iron accumulation and induced by oxidative stress [15,28], was negatively linked. TF gene expression was positively associated with other genes related to mitochondrial activity and the respiratory chain (such as PPARGC1B and MT-CO3).…”

Section: Intracellular Iron Deficiency Impairs Adipogenesismentioning

confidence: 81%

See 1 more Smart Citation

Fine-tuned iron availability is essential to achieve optimal adipocyte differentiation and mitochondrial biogenesis

et al. 2014

View full text Add to dashboard Cite

Aims/hypothesis Adipose tissue from obese and insulinresistant individuals showed altered expression of several iron-related genes in a recent study, suggesting that iron might have an important role in adipogenesis. To investigate this possible role, we aimed to characterise the effects of iron on adipocyte differentiation. Methods Intracellular iron deficiency was achieved using two independent approaches: deferoxamine administration (20 and 100 μmol/l) and transferrin knockdown (TF KD). The effects of added FeSO 4 , holo-transferrin and palmitate were studied during human and 3T3-L1 adipocyte differentiation. Finally, the relationship between iron-related and mitochondrialrelated genes was investigated in human adipose tissue. Results Most adipose tissue iron-related genes were predominantly expressed in adipocytes compared with stromal vascular cells. Of note, transferrin gene and protein expression increased significantly during adipocyte differentiation. Both deferoxamine and TF KD severely blunted adipocyte differentiation in parallel with increased inflammatory mRNAs. These effects were reversed in a dose-dependent manner after iron supplementation. Palmitate administration also led to a state of functional intracellular iron deficiency, with decreased Tf gene expression and iron uptake during adipocyte differentiation, which was reversed with transferrin co-treatment. On the other hand, iron in excess impaired differentiation, but this antiadipogenic effect was less pronounced than under iron chelation. Of interest, expression of several genes involved in mitochondrial biogenesis occurred in parallel with expression of iron-related genes both during adipogenesis and in human adipose tissue. Conclusions/interpretation Precise and fine-tuned iron availability is essential to achieve optimal adipocyte differentiation, possibly modulating adipocyte mitochondrial biogenesis.

show abstract

Section: Intracellular Iron Deficiency Impairs Adipogenesismentioning

confidence: 56%

Section: Intracellular Iron Deficiency Impairs Adipogenesismentioning

confidence: 81%

Fine-tuned iron availability is essential to achieve optimal adipocyte differentiation and mitochondrial biogenesis

et al. 2014

View full text Add to dashboard Cite

show abstract

“…An iron-restricted diet led to the opposite results, with low amounts of circulating free fatty acids and triglycerides (46). The reduction of iron levels by deferoxamine, an iron chelator, inhibited the development of adipocyte hypertrophy in mice and decreased macrophage infiltration (47). A parallel reduction in oxidative stress and inflammatory cytokine production, and improved glucose metabolism and insulin signaling, were observed in adipose tissue and skeletal muscle (47).…”

Section: Iron Affects Adipocyte Differentiation and Adipose Tissue Hymentioning

confidence: 99%

“…The reduction of iron levels by deferoxamine, an iron chelator, inhibited the development of adipocyte hypertrophy in mice and decreased macrophage infiltration (47). A parallel reduction in oxidative stress and inflammatory cytokine production, and improved glucose metabolism and insulin signaling, were observed in adipose tissue and skeletal muscle (47). The importance of iron in adipocyte differentiation and insulin action was confirmed by in vitro models: Incubation of rat adipocytes with excess iron resulted in decreased insulinstimulated glucose transport and increased lipolysis (48), whereas silencing of the iron-related genes transferrin and lactoferrin in murine cell lines resulted in impaired adipocyte differentiation and reduced insulin signaling (49).…”

Section: Iron Affects Adipocyte Differentiation and Adipose Tissue Hymentioning

confidence: 99%

Mechanisms Linking Glucose Homeostasis and Iron Metabolism Toward the Onset and Progression of Type 2 Diabetes

2015

View full text Add to dashboard Cite

OBJECTIVEThe bidirectional relationship between iron metabolism and glucose homeostasis is increasingly recognized. Several pathways of iron metabolism are modified according to systemic glucose levels, whereas insulin action and secretion are influenced by changes in relative iron excess. We aimed to update the possible influence of iron on insulin action and secretion and vice versa. RESEARCH DESIGN AND METHODSThe mechanisms that link iron metabolism and glucose homeostasis in the main insulin-sensitive tissues and insulin-producing b-cells were revised according to their possible influence on the development of type 2 diabetes (T2D). RESULTSThe mechanisms leading to dysmetabolic hyperferritinemia and hepatic overload syndrome were diverse, including diet-induced alterations in iron absorption, modulation of gluconeogenesis, heme-mediated disruption of circadian glucose rhythm, impaired hepcidin secretion and action, and reduced copper availability. Glucose metabolism in adipose tissue seems to be affected by both iron deficiency and excess through interaction with adipocyte differentiation, tissue hyperplasia and hypertrophy, release of adipokines, lipid synthesis, and lipolysis. Reduced heme synthesis and dysregulated iron uptake or export could also be contributing factors affecting glucose metabolism in the senescent muscle, whereas exercise is known to affect iron and glucose status. Finally, iron also seems to modulate b-cells and insulin secretion, although this has been scarcely studied. CONCLUSIONSIron is increasingly recognized to influence glucose metabolism at multiple levels. Body iron stores should be considered as a potential target for therapy in subjects with T2D or those at risk for developing T2D. Further research is warranted.Iron levels help to modulate the clinical manifestations of numerous systemic diseases. The importance of adequate amounts of iron for health and well-being in humans is well known. Iron is involved in binding and transporting oxygen and regulating cell growth and differentiation, as well as electron transport, DNA synthesis, and many important metabolic processes (1).From a clinical standpoint, assessing serum ferritin concentrations is a useful measure of iron storage. Ferritin is also an acute-phase reactant and, as such, is

show abstract

“…In patients with coronary artery disease, DFO was also shown to improve nitric oxide-mediated vasodilation [16]. More recently, DFO has been shown to be able to ameliorate adipocyte hypertrophy through suppression of oxidative stress, inflammatory cytokines and macrophage infiltration in obese diabetic mice [17].…”

Section: Expert Opinionmentioning

confidence: 99%

Potential therapeutic use of deferoxamine and mesenchymal stem cells in type-1 diabetes: assembling another piece of the jigsaw, in what is a complex puzzle

Egan¹

2013

Expert Opinion on Biological Therapy

View full text Add to dashboard Cite

Iron reduction by deferoxamine leads to amelioration of adiposity via the regulation of oxidative stress and inflammation in obese and type 2 diabetes KKAy mice

Abstract: T. Iron reduction by deferoxamine leads to amelioration of adiposity via the regulation of oxidative stress and inflammation in obese and type 2 diabetes KKAy mice.

Cited by 91 publications

References 45 publications

Fine-tuned iron availability is essential to achieve optimal adipocyte differentiation and mitochondrial biogenesis

Fine-tuned iron availability is essential to achieve optimal adipocyte differentiation and mitochondrial biogenesis

Mechanisms Linking Glucose Homeostasis and Iron Metabolism Toward the Onset and Progression of Type 2 Diabetes

Potential therapeutic use of deferoxamine and mesenchymal stem cells in type-1 diabetes: assembling another piece of the jigsaw, in what is a complex puzzle

Contact Info

Product

Resources

About