Abstract
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.
Original language | English (US) |
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Pages (from-to) | 3407-3419 |
Number of pages | 13 |
Journal | Journal of Immunology |
Volume | 200 |
Issue number | 10 |
DOIs | |
State | Published - May 15 2018 |
Bibliographical note
Publisher Copyright:Copyright 2018 by The American Association of Immunologists, Inc.