Epidermal Fatty Acid Binding Protein Promotes Skin Inflammation Induced by High-Fat Diet

Yuwen Zhang, Qiang Li, Enyu Rao, Yanwen Sun, Michael E. Grossmann, Rebecca J Morris, Margot P Cleary, Bing Li

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

Defining specific cellular and molecular mechanisms in most obesity-related diseases remains an important challenge. Here we report a serendipitous finding that consumption of a high-fat diet (HFD) greatly increased the occurrence of skin lesions in C57BL/6 mice. We demonstrated that HFD induced the accumulation of a specific type of CD11c+ macrophages in skin preceding detectable lesions. These cells primed skin to induce IL-1β and IL-18 signaling, which further promoted the cytokines IFN-γ- and IL-17-mediated skin inflammation. Mechanistically, epidermal fatty acid binding protein (E-FABP) was significantly upregulated in skin of obese mice, which coupled lipid droplet formation and NLRP3 inflammasome activation. Deficiency ofE-FABP in obese mice decreased recruitment ofCD11c+ macrophages in skin tissues, reduced production of IL-1β and IL-18, and consequently dampened activation of effector Tcells. Furthermore, E-FABP-deficient mice are completely resistant to HFD-induced skin lesions. Collectively, E-FABP represents a molecular sensor triggering HFD-induced skin inflammation.

Original languageEnglish (US)
Pages (from-to)953-964
Number of pages12
JournalImmunity
Volume42
Issue number5
DOIs
StatePublished - May 19 2015

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    Zhang, Y., Li, Q., Rao, E., Sun, Y., Grossmann, M. E., Morris, R. J., Cleary, M. P., & Li, B. (2015). Epidermal Fatty Acid Binding Protein Promotes Skin Inflammation Induced by High-Fat Diet. Immunity, 42(5), 953-964. https://doi.org/10.1016/j.immuni.2015.04.016