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Oliveras-Cañellas, Núria; Latorre, Jessica; Santos-González, Elena; Lluch, Aina; Ortega, Francisco; Mayneris-Perxachs, Jordi; Fernández-Real, José-Manuel; Moreno-Navarrete, José María
Biomedicine & pharmacotherapy, October 2023, 2023-10-00, 20231001, 2023-10-01, Letnik: 166Journal Article
The association among increased inflammation, disrupted iron homeostasis, and adipose tissue dysfunction in obesity has been widely recognized. However, the specific impact of inflammation on iron homeostasis during human adipogenesis and in adipocytes remains poorly understood. In this study, we investigated the effects of bacterial lipopolysaccharide (LPS) on iron homeostasis during human adipocyte differentiation, in fully differentiated adipocytes, and in human adipose tissue. We found that LPS-induced inflammation hindered adipogenesis and led to a gene expression profile indicative of intracellular iron accumulation. This was accompanied by increased expression of iron importers (TFRC and SLC11A2), markers of intracellular iron accumulation (FTH, CYBA, FTL, and LCN2), and decreased expression of iron exporter-related genes (SLC40A1), concomitant with elevated intracellular iron levels. Mechanistically, RNA-seq analysis and gene knockdown experiments revealed the significant involvement of iron importers SLC39A14, SLC39A8, and STEAP4 in LPS-induced intracellular iron accumulation in human adipocytes. Notably, markers of LPS signaling pathway-related inflammation were also associated with a gene expression pattern indicative of intracellular iron accumulation in human adipose tissue, corroborating the link between LPS-induced inflammation and iron accumulation at the tissue level. In conclusion, our findings demonstrate that induction of adipocyte inflammation disrupts iron homeostasis, resulting in adipocyte iron overload. Display omitted •LPS-induced inflammation promotes intracellular iron accumulation during adipocyte differentiation and in human adipocytes.•SLC39A14, SLC39A8 and STEAP4 are involved in LPS-induced intracellular iron accumulation.•The link between LPS-induced inflammation and iron accumulation is confirmed in human adipose tissue.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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