Dataset Information

Lactoferrin gene knockdown leads to similar effects to iron chelation in human adipocytes.

ABSTRACT: In human and mice adipose tissue, lactoferrin (LTF) has been found to be associated with increased adipogenesis and decreased inflammatory markers. Here, we aimed to investigate the effects of LTF knockdown (KD) in human adipocyte differentiation. In addition, the effects of exogenous LTF administration and iron chelation [using deferoxamine (DFO, 10 ?M)] were tested. In both subcutaneous and visceral pre-adipocytes, LTF KD led to decrease significantly adipogenic, lipogenic and insulin signalling-related gene expression and a significant increase in the gene expression of inflammatory mediators. Human lactoferrin (hLf, 1 ?M) administration led to recover adipocyte differentiation in LTF KD pre-adipocytes. Interestingly, iron chelation triggered similar effects to LTF KD, decreasing significantly adipogenic gene expressions. Of note, DFO (10 ?M) and hLf (1 and 10 ?M) co-administration led to a dose-dependent recovery of adipocyte differentiation. These new data reveal that endogenous LTF biosynthesis during human adipocyte differentiation is essential to achieve this process, possibly, modulating adipocyte iron homoeostasis. hLf administration might be a useful therapeutic target in obesity-associated adipose tissue dysfunction.

SUBMITTER: Moreno-Navarrete JM

PROVIDER: S-EPMC3955146 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Lactoferrin gene knockdown leads to similar effects to iron chelation in human adipocytes.

Moreno-Navarrete José María JM Ortega Francisco F Moreno Maria M Serrano Marta M Ricart Wifredo W Fernández-Real José Manuel JM

Journal of cellular and molecular medicine 20140226 3

In human and mice adipose tissue, lactoferrin (LTF) has been found to be associated with increased adipogenesis and decreased inflammatory markers. Here, we aimed to investigate the effects of LTF knockdown (KD) in human adipocyte differentiation. In addition, the effects of exogenous LTF administration and iron chelation [using deferoxamine (DFO, 10 μM)] were tested. In both subcutaneous and visceral pre-adipocytes, LTF KD led to decrease significantly adipogenic, lipogenic and insulin signalli ...[more]

PMID: 24571258

Similar Datasets

Project description:BackgroundPatients with myelodysplastic syndrome (MDS) require chronic red blood cell (RBC) transfusion due to anemia. Multiple RBC transfusions cause secondary iron overload and subsequent excessive generation of reactive oxygen species (ROS), which leads to mutations, cell death, organ failure, and inferior disease outcomes. We hypothesize that iron loading promotes AML development by increasing oxidative stress and disrupting important signaling pathways in the bone marrow cells (BMCs). Conversely, iron chelation therapy (ICT) may reduce AML risk by lowering iron burden in the iron-loaded animals.MethodsWe utilized a radiation-induced acute myeloid leukemia (RI-AML) animal model. Iron overload was introduced via intraperitoneal injection of iron dextran, and iron chelation via oral gavage of deferasirox. A total of 86 irradiated B6D2F1 mice with various levels of iron burden were monitored for leukemia development over a period of 70 weeks. The Kaplan-Meier estimator was utilized to assess AML free survival. In addition, a second cohort of 30 mice was assigned for early analysis at 5 and 7 months post-irradiation. The BMCs of the early cohort were assessed for alterations of signaling pathways, DNA damage response and gene expression. Statistical significance was established using Student's t-test or ANOVA.ResultsIron loading in irradiated B6D2F1 mice accelerated RI-AML development. However, there was a progressive decrease in AML risk for irradiated mice with increase in iron burden from 7.5 to 15 to 30 mg. In addition, ICT decreased AML incidence in the 7.5 mg iron-loaded irradiated mice, while AML onset was earlier for the 30 mg iron-loaded irradiated mice that received ICT. Furthermore, analysis of BMCs from irradiated mice at earlier intervals revealed accelerated dysregulation of signaling pathways upon iron loading, while ICT partially mitigated the effects.ConclusionsWe concluded that iron is a promoter of leukemogenesis in vivo up to a peak iron dose, but further iron loading decreases AML risk by increasing cell death. ICT can partially mitigate the adverse effects of iron overload, and to maximize its benefit this intervention should be undertaken prior to the development of extreme iron overload.

Dataset Information

Lactoferrin gene knockdown leads to similar effects to iron chelation in human adipocytes.

Publications

Lactoferrin gene knockdown leads to similar effects to iron chelation in human adipocytes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets