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Hepatic and adipocyte cells respond differentially to iron overload, hypoxic and inflammatory challenge

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Abstract

Adipose tissue secretes numerous pro-inflammatory cytokines, such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α that can lead to insulin resistance (IR). In the liver, both IL-6 and TNF-α induce IR by inhibiting phosphorylation or ubiquitination of IRS1. In IR development, Fe is a risk factor in type-2 diabetes development. We studied the expression of genes related to inflammation, hypoxia, and mitochondrial function in hepatic (HepG2) and adipose (3T3-L1) cells. HepG2 and 3T3-L1 cells were incubated with 20 μM Fe, 40 μM Fe, or 40 μM Fe/20 mM glucose for 7 days and then challenged with 20 ng/ml IL-6 and/or 100 μM CoCl2 for 20 h. We measured intracellular Fe levels and the relative expression of hepcidin, NF-κB, IL-6, TNF-α, hypoxia inducible factor 1α (HIF-1α), and mitofusin 2 (Mfn-2) mRNA using qRT-PCR. The intracellular Fe concentration in HepG2 cells did not change with 20 or 40 μM Fe. However, levels were decreased with Fe/glucose and IL-6 and/or CoCl2. 3T3-L1 cells showed an increase in intracellular Fe with high Fe plus either IL-6 or CoCl2. HepG2 cells incubated with 40 μM Fe alone or Fe/glucose and challenged with IL-6 and/or CoCl2 showed increased IL-6, NF-κB, and TNF-α mRNA expression and decreased mRNA expression of Mfn-2 in all experimental conditions. 3T3-L1 cells incubated with 40 μM Fe alone or Fe/glucose and challenged with IL-6 showed increased NF-κB mRNA expression and decreased Mfn-2 expression in all experimental conditions. Thus, high Fe, inflammation, and hypoxia trigger the expression of genes related to inflammation and Fe metabolism in HepG2 cells, in 3T3-L1 cells the same stimuli increased NF-kB and hepcidin expression.

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Acknowledgments

This research was supported by the Diabetes and Endocrinology Society of Chile (SOCHED) and FONDECYT No. 1085173 and 1110080.

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  1. Micronutrient Laboratory, Nutrition Institute and Food Technology, University of Chile, El Líbano 5524, Macul, Santiago, Chile

    M. Andrews & M. Arredondo

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Andrews, M., Arredondo, M. Hepatic and adipocyte cells respond differentially to iron overload, hypoxic and inflammatory challenge. Biometals 25, 749–759 (2012). https://doi.org/10.1007/s10534-012-9543-9

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