Proadipogenic effects of lactoferrin in human subcutaneous and visceral preadipocytes

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 ^Ser473AKT 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 ^Ser473AKT phosphorylation. In addition to these adipogenic effects, lactoferrin decreased significantly AMPK activity (reducing ^pThr172AMPK and ^pSer79ACC) and RB1 activity (increasing the ^pser807/811RB1/RB1 ratio). In conclusion, these results suggest that lactoferrin promotes adipogenesis in human adipocytes by enhancing insulin signaling and inhibiting RB1 and AMPK activities.