Iron Inhibits the Secretion of Apolipoprotein E in Cultured Human Adipocytes

Britton, L.; Bridle, Kim R.; Jaskowski, L.; He, Jing; Ng, Choaping; Ruelcke, Jayde E.; Mohamed, Ahmed; Reiling, Janske; Santrampurwala, Nishreen; Hill, Michelle M.; Whitehead, Jonathan P.; Subramaniam, V. Nathan; Crawford, Darrell H. G.

doi:10.1016/j.jcmgh.2018.04.005

Cited by 10 publications

(10 citation statements)

References 18 publications

(19 reference statements)

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“…For example, ApoE is proposed to protect against NASH (non-alcoholic steatohepatitis) as ApoE knockout mice were characterized by hepatosteatosis [53]. A link to iron was identified in a recent SILAC proteomic study in which adipocytes were treated with ferric ammonium citrate (FAC, a source of NTBI) resulting in an 11-fold increase in ApoE (amongst two other markers), although ApoE secretion was reduced by >55% [53]. Further studies are needed to elucidate the mechanism underlying increased ApoE expression in spite of its reduced secretion.…”

Section: Interactions Between Iron and Lipids In Model Systemsmentioning

confidence: 99%

Links Between Iron and Lipids: Implications in Some Major Human Diseases

et al. 2018

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Maintenance of iron homeostasis is critical to cellular health as both its excess and insufficiency are detrimental. Likewise, lipids, which are essential components of cellular membranes and signaling mediators, must also be tightly regulated to hinder disease progression. Recent research, using a myriad of model organisms, as well as data from clinical studies, has revealed links between these two metabolic pathways, but the mechanisms behind these interactions and the role these have in the progression of human diseases remains unclear. In this review, we summarize literature describing cross-talk between iron and lipid pathways, including alterations in cholesterol, sphingolipid, and lipid droplet metabolism in response to changes in iron levels. We discuss human diseases correlating with both iron and lipid alterations, including neurodegenerative disorders, and the available evidence regarding the potential mechanisms underlying how iron may promote disease pathogenesis. Finally, we review research regarding iron reduction techniques and their therapeutic potential in treating patients with these debilitating conditions. We propose that iron-mediated alterations in lipid metabolic pathways are involved in the progression of these diseases, but further research is direly needed to elucidate the mechanisms involved.

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Section: Interactions Between Iron and Lipids In Model Systemsmentioning

confidence: 99%

Links Between Iron and Lipids: Implications in Some Major Human Diseases

et al. 2018

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“…A number of clinical and experimental studies have shown that ApoE or ApoE deficient (ApoE −/- ) and iron both were associated the development of AD [ 4 , 5 ] and atherosclerosis [ [6] , [7] , [8] ]. Studies in vitro have demonstrated that iron has a role in regulating ApoE expression and secretion in different types of cells [ 9 , 10 ]. In addition, toll-like receptor (TLR-4) and inflammatory factors including interleukin-6 (IL-6) has been found to play an important role in the regulation of hepcidin (a principal regulator of iron metabolism) expression, thus affecting systemic iron homeostasis [ [11] , [12] , [13] ], while ApoE has been demonstrated to be closely linked with both pro-inflammatory and anti-inflammatory cytokines [ 14 , 15 ], being able to inhibit TLR-4-mediated macrophage or glial activation and to suppress IL-6 and other inflammatory factors in vitro and in vivo [ [16] , [17] , [18] ].…”

Section: Introductionmentioning

confidence: 99%

Apolipoprotein E deficiency induces a progressive increase in tissue iron contents with age in mice

Qian

Bao

et al. 2021

Redox Biology

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“…The decrease in protein secretion might have occurred through inhibition of the secretory lysosomal pathway, as was observed in a previous study, where Wu and coworkers showed that iron oxide NPs reduced LPS induced secretion of IL-1β (but not TNFα) through impairment of lysosomal degradation and increase in lysosomal permeability [ 55 ]. Similarly, Britton and coworkers showed that iron affects the secretion of more than 60 proteins in cultured human adipocytes, including several signaling proteins [ 56 ]. Based on the changes in secretion, they propose that iron might have a specific effect on proteins secreted via the classic protein secretion pathway.…”

Section: Discussionmentioning

confidence: 99%

Analysis of the Direct and Indirect Effects of Nanoparticle Exposure on Microglial and Neuronal Cells In Vitro

Lojk

Babič

Sušjan

et al. 2020

IJMS

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Environmental or biomedical exposure to nanoparticles (NPs) can results in translocation and accumulation of NPs in the brain, which can lead to health-related problems. NPs have been shown to induce toxicity to neuronal cells through several direct mechanisms, but only a few studies have also explored the indirect effects of NPs, through consequences due to the exposure of neighboring cells to NPs. In this study, we analysed possible direct and indirect effects of NPs (polyacrylic acid (PAA) coated cobalt ferrite NP, TiO2 P25 and maghemite NPs) on immortalized mouse microglial cells and differentiated CAD mouse neuronal cells in monoculture (direct toxicity) or in transwell co-culture system (indirect toxicity). We showed that although the low NP concentrations (2–25 µg/mL) did not induce changes in cell viability, cytokine secretion or NF-κB activation of microglial cells, even low NP concentrations of 10 µg/mL can affect the cells and change their secretion of protein stress mediators. These can in turn influence neuronal cells in indirect exposure model. Indirect toxicity of NPs is an important and not adequately assessed mechanism of NP toxicity, since it not only affects cells on the exposure sites, but through secretion of signaling mediators, can also affect cells that do not come in direct contact with NPs.

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Iron Inhibits the Secretion of Apolipoprotein E in Cultured Human Adipocytes

Cited by 10 publications

References 18 publications

Links Between Iron and Lipids: Implications in Some Major Human Diseases

Links Between Iron and Lipids: Implications in Some Major Human Diseases

Apolipoprotein E deficiency induces a progressive increase in tissue iron contents with age in mice

Analysis of the Direct and Indirect Effects of Nanoparticle Exposure on Microglial and Neuronal Cells In Vitro

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