Iron overload by transferrin receptor protein 1 regulation plays an important role in palmitate‐induced insulin resistance in human skeletal muscle cells

Cui, Rihua; Choi, Sung‐E; Kim, Tae Ho; Lee, Hwa Joung; Lee, Soo Jin; Kang, Yup; Jeon, Ja Young; Kim, Hae Jin; Lee, Kwan‐Woo

doi:10.1096/fj.201800448r

Cited by 26 publications

(24 citation statements)

References 58 publications

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“…In our study, the concentrations of Zn, Cu, and Fe in maternal serum in the 10-14th week were not associated with LGA risk, although these microelements are also associated with metabolic disorders, such as insulin resistance as well as diabetes mellitus and obesity [16][17][18]. In their optimal levels, they also have antioxidant and anti-inflammatory properties, and their deficiency or excess may increase inflammation and oxidative stress [15].…”

Section: Discussionmentioning

confidence: 46%

“…Microelements such as selenium (Se), zinc (Zn), copper (Cu), and iron (Fe) have anti-inflammatory and antioxidant properties, and their deficiency or excess can increase inflammation and oxidative stress [14,15]. These microelements are involved in insulin signal cascade regulation, glucose metabolism, and the functions of many hormones [11,[16][17][18]. They also affect cell proliferation and differentiation [2,14,19].…”

Section: Introductionmentioning

confidence: 99%

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Serum Microelements in Early Pregnancy and their Risk of Large-for-Gestational Age Birth Weight

Lewandowska

Lubiński

2020

Nutrients

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Excessive birth weight has serious perinatal consequences, and it “programs” long-term health. Mother’s nutritional status can be an important element in fetal “programming”; microelements such as selenium (Se), zinc (Zn), copper (Cu), and iron (Fe) are involved in many metabolic processes. However, there are no studies assessing the relationship of the microelements in the peri-conceptual period with the risk of excessive birth weight. We performed a nested case control study of serum microelements’ levels in the 10–14th week of pregnancy and assessed the risk of large-for-gestational age (LGA) newborns using the data from a prospective cohort of pregnant women recruited in 2015–2016 in Poznań, Poland. Mothers delivering LGA newborns (n = 66) were examined with matched mothers delivering appropriate-for-gestational age (AGA) newborns (n = 264). Microelements’ levels were quantified using mass spectrometry. The odds ratios of LGA (and 95% confidence intervals) were calculated by multivariate logistic regression. In the whole group, women with the lowest quartile of Se had a 3 times higher LGA risk compared with women in the highest Se quartile (AOR = 3.00; p = 0.013). Importantly, the result was sustained in the subgroup of women with the normal pre-pregnancy BMI (AOR = 4.79; p = 0.033) and in women with a male fetus (AOR = 6.28; p = 0.004), but it was not sustained in women with a female fetus. There were no statistical associations between Zn, Cu, and Fe levels and LGA. Our study provides some preliminary evidence for the relationships between lower serum Se levels in early pregnancy and a higher risk of large-for-gestational age birth weight. Appropriate Se intake in the periconceptual period may be important for optimal fetal growth.

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Section: Discussionmentioning

confidence: 46%

Section: Introductionmentioning

confidence: 99%

Serum Microelements in Early Pregnancy and their Risk of Large-for-Gestational Age Birth Weight

Lewandowska

Lubiński

2020

Nutrients

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“…Whereas iron deficiency leads to anaemia (Zimmermann & Hurrell, 2007), high body iron stores have been associated with metabolic dysfunction and the development of type 2 diabetes (Jehn, Clark, & Guallar, 2004; Jiang et al., 2004). The mechanisms linking iron and metabolic dysfunction are incompletely understood (Fernández‐Real, McClain, & Manco, 2015), but some pre‐clinical evidence indicates that excess muscle iron impairs peripheral insulin signalling (Cui et al., 2019). Although whole‐body iron stores vary markedly among adults with obesity (Aigner et al., 2014), it was reported that markers of iron content in skeletal muscle correlated with BMI, suggestive of increased muscle iron storage in obesity (Moreno‐Navarrete et al., 2016).…”

Section: Discussionmentioning

confidence: 99%

Skeletal muscle ferritin abundance is tightly related to plasma ferritin concentration in adults with obesity

Ryan

Foug

Gioscia‐Ryan

et al. 2020

Experimental Physiology

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New Findings What is the central question of this study?Obesity is associated with complex perturbations to iron homeostasis: is plasma ferritin concentration (a biomarker of whole‐body iron stores) related to the abundance of ferritin (the key tissue iron storage protein) in skeletal muscle in adults with obesity? What is the main finding and its importance?Plasma ferritin concentration was tightly correlated with the abundance of ferritin in skeletal muscle, and this relationship persisted when accounting for sex, age, body mass index and plasma C‐reactive protein concentration. Our findings suggest that skeletal muscle may be an important iron store. Abstract Obesity is associated with complex perturbations to whole‐body and tissue iron homeostasis. Recent evidence suggests a potentially important influence of iron storage in skeletal muscle on whole‐body iron homeostasis, but this association is not clearly resolved. The primary aim of this study was to assess the relationship between whole‐body and skeletal muscle iron stores by measuring the abundance of the key iron storage (ferritin) and import (transferrin receptor) proteins in skeletal muscle, as well as markers of whole‐body iron homeostasis in men (n = 19) and women (n = 43) with obesity. Plasma ferritin concentration (a marker of whole‐body iron stores) was highly correlated with muscle ferritin abundance (r = 0.77, P = 2 × 10−13) and negatively associated with muscle transferrin receptor abundance (r = −0.76, P = 1 × 10−12). These relationships persisted when accounting for sex, age, BMI and plasma C‐reactive protein concentration. In parallel with higher whole‐body iron stores in our male versus female participants, men had 2.2‐fold higher muscle ferritin abundance (P = 1 × 10−4) compared with women. In accordance with lower muscle iron storage, women had 2.7‐fold higher transferrin receptor abundance (P = 7 × 10−10) compared with men. We conclude that muscle iron storage and import proteins are tightly and independently related to plasma ferritin concentration in adults with obesity, suggesting that skeletal muscle may be an underappreciated iron store.

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“…Moreover, Zhang et al (20) reported that calcium channel blockers (CCBs) ameliorated iron overload-associated hepatic fibrosis by altering iron transport, and indicated that ccBs are potential therapeutic agents for iron overload-induced diseases. calcium was reported to modulate receptor-mediated endocytosis and, as TfR1 modulates iron influx through this pathway, it was further demonstrated that calcium could antagonize iron-TF-TfR1 complex internalization and, thus, modulate iron uptake (21).…”

Section: Calcium Chelator Bapta-am Protects Against Iron Overload-induced Chondrocyte Mitochondrial Dysfunction and Cartilage Degeneratiomentioning

confidence: 97%

Calcium chelator BAPTA‑AM protects against iron overload‑induced chondrocyte mitochondrial dysfunction and cartilage degeneration

Jing

Wang

Du³

et al. 2021

Int J Mol Med

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Osteoarthritis (OA) is a common joint disease that is characterized by cartilage degradation. Iron deposition in the joints is common during the pathogenic progression of OA and recent studies have indicated that iron overload is an important contributor to OA progression. calcium chelators have been reported to inhibit iron influx via modulating transferrin receptor protein 1 internalization, and they have been identified as a potential approach to the treatment of iron overload-induced diseases. The aim of the present study was to investigate the effect of calcium chelators on the progression of iron overload-induced OA. Primary chondrocytes were treated with various concentrations of ferric ammonium citrate (FAc) to mimic iron overload in vitro, followed by co-treatment with the calcium chelator BAPTA acetoxymethyl ester (BAPTA-AM). Subsequently, intracellular iron levels, cell viability, reactive oxygen species (ROS) levels, mitochondrial function and morphological changes, as well as MMP levels, were detected using commercial kits. It was demonstrated that FAC treatment significantly promoted chondrocyte apoptosis and the expression of MMPs, and these effects were reversed by co-treatment with BAPTA-AM. Moreover, BAPTA-AM suppressed iron influx into chondrocytes and inhibited iron overload-induced ROS production and mitochondrial dysfunction. These results indicated that calcium chelators may be of value in the treatment of iron metabolism-related diseases and iron overload-induced OA progression.

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Iron overload by transferrin receptor protein 1 regulation plays an important role in palmitate‐induced insulin resistance in human skeletal muscle cells

Cited by 26 publications

References 58 publications

Serum Microelements in Early Pregnancy and their Risk of Large-for-Gestational Age Birth Weight

Serum Microelements in Early Pregnancy and their Risk of Large-for-Gestational Age Birth Weight

Skeletal muscle ferritin abundance is tightly related to plasma ferritin concentration in adults with obesity

Calcium chelator BAPTA‑AM protects against iron overload‑induced chondrocyte mitochondrial dysfunction and cartilage degeneration

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