Inflammatory response to bacterial lipopolysaccharide drives iron accumulation in human adipocytes
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 in...
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Elsevier
2023-10-01
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Series: | Biomedicine & Pharmacotherapy |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S075333222301226X |
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author | Núria Oliveras-Cañellas Jessica Latorre Elena Santos-González Aina Lluch Francisco Ortega Jordi Mayneris-Perxachs José-Manuel Fernández-Real José María Moreno-Navarrete |
author_facet | Núria Oliveras-Cañellas Jessica Latorre Elena Santos-González Aina Lluch Francisco Ortega Jordi Mayneris-Perxachs José-Manuel Fernández-Real José María Moreno-Navarrete |
author_sort | Núria Oliveras-Cañellas |
collection | DOAJ |
description | 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. |
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language | English |
last_indexed | 2024-03-12T01:10:58Z |
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spelling | doaj.art-a15e43f200474ffdbcf610c7efb2282e2023-09-14T04:53:01ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-10-01166115428Inflammatory response to bacterial lipopolysaccharide drives iron accumulation in human adipocytesNúria Oliveras-Cañellas0Jessica Latorre1Elena Santos-González2Aina Lluch3Francisco Ortega4Jordi Mayneris-Perxachs5José-Manuel Fernández-Real6José María Moreno-Navarrete7Department of Diabetes, Endocrinology and Nutrition, Institut d′Investigació Biomèdica de Girona (IdIBGi), CIBEROBN (CB06/03/010) and Instituto de Salud Carlos III (ISCIII), Girona, SpainDepartment of Diabetes, Endocrinology and Nutrition, Institut d′Investigació Biomèdica de Girona (IdIBGi), CIBEROBN (CB06/03/010) and Instituto de Salud Carlos III (ISCIII), Girona, SpainDepartment of Diabetes, Endocrinology and Nutrition, Institut d′Investigació Biomèdica de Girona (IdIBGi), CIBEROBN (CB06/03/010) and Instituto de Salud Carlos III (ISCIII), Girona, SpainDepartment of Diabetes, Endocrinology and Nutrition, Institut d′Investigació Biomèdica de Girona (IdIBGi), CIBEROBN (CB06/03/010) and Instituto de Salud Carlos III (ISCIII), Girona, SpainDepartment of Diabetes, Endocrinology and Nutrition, Institut d′Investigació Biomèdica de Girona (IdIBGi), CIBEROBN (CB06/03/010) and Instituto de Salud Carlos III (ISCIII), Girona, SpainDepartment of Diabetes, Endocrinology and Nutrition, Institut d′Investigació Biomèdica de Girona (IdIBGi), CIBEROBN (CB06/03/010) and Instituto de Salud Carlos III (ISCIII), Girona, SpainDepartment of Diabetes, Endocrinology and Nutrition, Institut d′Investigació Biomèdica de Girona (IdIBGi), CIBEROBN (CB06/03/010) and Instituto de Salud Carlos III (ISCIII), Girona, Spain; Department of Medicine, Universitat de Girona, Girona, Spain; Correspondence to: Department of Diabetes, Endocrinology and Nutrition (UDEN), Biomedical Research Institute of Girona “Dr Josep Trueta”, Hospital of Girona “Dr Josep Trueta”, Carretera de França s/n, 17007 Girona, Spain.Department of Diabetes, Endocrinology and Nutrition, Institut d′Investigació Biomèdica de Girona (IdIBGi), CIBEROBN (CB06/03/010) and Instituto de Salud Carlos III (ISCIII), Girona, Spain; Correspondence to: Section of Nutrition, Eumetabolism and Health, Biomedical Research Institute of Girona “Dr Josep Trueta”, C/ Dr.Castany s/n, 17190 Salt, Spain.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.http://www.sciencedirect.com/science/article/pii/S075333222301226XAdipocyteAdipogenesisInflammationIronGene knockdownRNA-seq |
spellingShingle | Núria Oliveras-Cañellas Jessica Latorre Elena Santos-González Aina Lluch Francisco Ortega Jordi Mayneris-Perxachs José-Manuel Fernández-Real José María Moreno-Navarrete Inflammatory response to bacterial lipopolysaccharide drives iron accumulation in human adipocytes Biomedicine & Pharmacotherapy Adipocyte Adipogenesis Inflammation Iron Gene knockdown RNA-seq |
title | Inflammatory response to bacterial lipopolysaccharide drives iron accumulation in human adipocytes |
title_full | Inflammatory response to bacterial lipopolysaccharide drives iron accumulation in human adipocytes |
title_fullStr | Inflammatory response to bacterial lipopolysaccharide drives iron accumulation in human adipocytes |
title_full_unstemmed | Inflammatory response to bacterial lipopolysaccharide drives iron accumulation in human adipocytes |
title_short | Inflammatory response to bacterial lipopolysaccharide drives iron accumulation in human adipocytes |
title_sort | inflammatory response to bacterial lipopolysaccharide drives iron accumulation in human adipocytes |
topic | Adipocyte Adipogenesis Inflammation Iron Gene knockdown RNA-seq |
url | http://www.sciencedirect.com/science/article/pii/S075333222301226X |
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