title: Proadipogenic effects of lactoferrin in human subcutaneous and visceral preadipocytes.
abstract: Lactoferrin has been associated with insulin sensitivity in vivo and in vitro studies. We aimed to test the effects of lactoferrin on human subcutaneous and visceral preadipocytes. Human subcutaneous and visceral preadipocytes were cultured with increasing lactoferrin (hLf, 0.1, 1, 10 μM) under differentiation conditions. The effects of lactoferrin on adipogenesis were studied through the expression of different adipogenic and inflammatory markers, AMPK activation and Retinoblastoma 1 (RB1) activity. The response to insulin was evaluated through (Ser473)AKT phosphorylation. In both subcutaneous and visceral preadipocytes, lactoferrin (1 and 10 μM) increased adipogenic gene expressions and protein levels (fatty acid synthase, PPARγ, FABP4, ADIPOQ, ACC and STAMP2) and decreased inflammatory markers (IL8, IL6 and MCP1) dose-dependently in parallel to increased insulin-induced (Ser473)AKT phosphorylation. In addition to these adipogenic effects, lactoferrin decreased significantly AMPK activity (reducing (pThr172)AMPK and (pSer79)ACC) and RB1 activity (increasing the (pser807/811)RB1/RB1 ratio). In conclusion, these results suggest that lactoferrin promotes adipogenesis in human adipocytes by enhancing insulin signaling and inhibiting RB1 and AMPK activities.
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, CIBEROBN Fisiopatología de la Obesidad y Nutrición CB06/03/010 and Girona Biomedical Research Institute, Girona, Spain.
authors.forename: José María
authors.initials: JM
authors.lastname: Moreno-Navarrete
authors.forename: Francisco
authors.initials: F
authors.lastname: Ortega
authors.forename: Mònica
authors.initials: M
authors.lastname: Sabater
authors.forename: Wifredo
authors.initials: W
authors.lastname: Ricart
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Fernández-Real
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D017667:Adipocytes / Q000378:metabolism*; D050156:Adipogenesis; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D005809:Genes, Regulator; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D007781:Lactoferrin / Q000494:pharmacology*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D016160:Retinoblastoma Protein / Q000378:metabolism
chemical_list: D015415:Biomarkers; D047495:PPAR gamma; D016160:Retinoblastoma Protein; D055372:AMP-Activated Protein Kinases; D007781:Lactoferrin