title: 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 μM)] 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 μM) 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 μM) and hLf (1 and 10 μM) 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.
authors.affiliation: Service 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.
authors.forename: José María
authors.initials: JM
authors.lastname: Moreno-Navarrete
authors.forename: Francisco
authors.initials: F
authors.lastname: Ortega
authors.forename: Maria
authors.initials: M
authors.lastname: Moreno
authors.forename: Marta
authors.initials: M
authors.lastname: Serrano
authors.forename: Wifredo
authors.initials: W
authors.lastname: Ricart
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Fernández-Real
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D050156:Adipogenesis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D003676:Deferoxamine / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D006801:Humans; D007249:Inflammation / Q000473:pathology; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000494:pharmacology*; D007781:Lactoferrin / Q000235:genetics* / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D007502:Iron Chelating Agents; D007501:Iron; D007781:Lactoferrin; D003676:Deferoxamine
keywords: adipocytes; adipogenesis; iron metabolism; lactoferrin