Lactoferrin, a Pleiotropic Protein in Health and Disease

Significance: Lactoferrin (Lf) is a nonheme iron-binding glycoprotein strongly expressed in human and bovinemilk and it plays many functions during infancy such as iron homeostasis and defense against microorganisms. In humans, Lf is mainly expressed in mucosal epithelial and immune cells. Growing evidence suggests multiple physiological roles for Lf after weaning. Recent Advances: The aim of this review is to highlight the recent advances concerning multifunctional Lf activities. Critical Issues: First, we will provide an overview of the mechanisms related to Lf intrinsic synthesis or intestinal absorption as well as its interaction with a wide spectrum of mammalian receptors and distribution in organs and cell types. Second, we will discuss the large variety of its physiological functions such as iron homeostasis, transportation, immune regulation, oxidative stress, inflammation, and apoptosis while specifying the mechanisms of action. Third, we will focus on its recent physiopathology implication in metabolic disorders, including obesity, type 2 diabetes, and cardiovascular diseases. Additional efforts are necessary before suggesting the potential use of Lf as a diagnostic marker or as a therapeutic tool. Future Directions: The main sources of Lf in human cardiometabolic disorders should be clarified to identify new perspectives for future research and develop new strategies using Lf in therapeutics.