Stearic Acid Induces CD11c Expression in Proinflammatory Macrophages via Epidermal Fatty Acid Binding Protein

Obesity is associated with elevated levels of free fatty acids (FAs) and proinflammatory CD11c⁺ macrophages. However, whether and how free FAs contribute to CD11c⁺ macrophage differentiation and proinflammatory functions remain unclear. Here we report that dietary saturated FAs, but not unsaturated FAs, promoted the differentiation and function of CD11c⁺ macrophages. Specifically, we demonstrated that stearic acid (SA) significantly induced CD11c expression in monocytes through activation of the nuclear retinoid acid receptor. More importantly, cytosolic expression of epidermal FA binding protein (E-FABP) in monocytes/macrophages was shown to be critical to the mediation of the SA-induced effect. Depletion of E-FABP not only inhibited SA-induced CD11c upregulation in macrophages in vitro but also abrogated high-saturated-fat diet-induced skin lesions in obese mouse models in vivo. Altogether, our data demonstrate a novel mechanism by which saturated FAs promote obesity-associated inflammation through inducing E-FABP/retinoid acid receptor-mediated differentiation of CD11c⁺ macrophages.