Abstract
Objective:
Lactoferrin is a pleiotropic glycoprotein of the innate immune system with known effects on immunomodulation and cell differentiation. To gain an insight into the interaction among obesity, inflammation and insulin action, we aimed to examine the effects of lactoferrin on adipogenesis and the response to insulin in human hepatocarcinoma (HepG2) and 3T3-L1 cell lines.
Design:
The cells were cultured with increasing lactoferrin concentration under non-inflammatory, inflammatory and standard conditions. The response to insulin was evaluated through 473SerAKT phosphorylation. The effects of lactoferrin on adipogenesis were studied through the expression of different lipogenic markers, AMP-activated protein kinase (AMPK) activation, retinoblastoma (Rb) activity and Oil Red O staining in 3T3-L1 cells.
Results:
Lactoferrin increased dose-dependent insulin-induced 473SerAKT phosphorylation in both cell lines. Inflammation-induced decreased 473SerAKT phosphorylation was also rescued by lactoferrin. In addition, lactoferrin led to increased p172ThrAMPK during 3T3-L1 differentiation and to decreased adipogenesis (as shown by decreased expression of fatty acid synthase, acetyl-coenzyme A carboxylase-α and peroxisome proliferator-activated receptor-γ in parallel with decreased formation of lipid droplets). Lactoferrin also increased dose-dependent Rb activity (expression and hypophosphorylation) during 3T3-L1 differentiation.
Conclusion:
Lactoferrin administration increased insulin-induced 473SerAKT phosphorylation, even in those conditions wherein the response to insulin was downregulated, and led to blunted adipogenesis in the context of increased p172ThrAMPK and Rb activity.
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This work was partially supported by research grants from the Ministerio de Educación y Ciencia (SAF2008-0273).
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Moreno-Navarrete, J., Ortega, F., Ricart, W. et al. Lactoferrin increases 172ThrAMPK phosphorylation and insulin-induced p473SerAKT while impairing adipocyte differentiation. Int J Obes 33, 991–1000 (2009). https://doi.org/10.1038/ijo.2009.143
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DOI: https://doi.org/10.1038/ijo.2009.143
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