Stearic acid induces CD11c expression in proinflammatory macrophages via epidermal fatty acid binding protein

Jun Zeng, Yuwen Zhang, Jiaqing Hao, Yanwen Sun, Shujun Liu, David A. Bernlohr, Edward R. Sauter, Margot P. Cleary, Jill Suttles, Bing Li

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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 languageEnglish (US)
Pages (from-to)3407-3419
Number of pages13
JournalJournal of Immunology
Volume200
Issue number10
DOIs
StatePublished - May 15 2018

Bibliographical note

Funding Information:
This work was supported by start-up funds from the University of Louisville and by Grants R01CA177679 and R01CA180986 from the National Cancer Institute (Bethesda, MD). We thank Dr. Hyeran Jang for assistance with design of the custom rodent diets made by Research Diets, Inc.

Publisher Copyright:
Copyright 2018 by The American Association of Immunologists, Inc.

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